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Freeze Dried Chitosan/ Poly-(Glutamic Acid) Microparticles For Intestinal Delivery Of Lansoprazole
Mangla Nand Singh, Hemant KS Yadav, Munshi Ram, Shivakumar H G
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00037]


Microneedles As Transdermal Delivery Systems: Combination With Other Enhancing Strategies
Nava-Arzaluz M.G. Calderón-Lojero I. Quintanar-Guerrero D. Villalobos-García R. Ganem-Quintanar A
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00041]


“Metabolic aspects” in inflammatory bowel diseases
Kaser, M.D.
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00042]


Foam preparations for the treatment of ulcerative colitis
Burr J. Loew and Corey A. Siegel
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00043]


Cell therapies for inflammatory bowel disease
Julián Panés, Orlando García‐Bosch, Azucena Salas and Daniel Benitez
[Abstract] [Purchase Article] [PMID: 22023203 PubMed - indexed for MEDLINE] [BSP/CDD/E-Pub/00044]


What is the optimal treatment for anemia in inflammatory bowel disease?
Alexandra J Kent MRCP, Victoria J Blackwell MRCP and Simon PL Travis DPhil FRCP
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00045]


Feasibility of Assam Bora rice starch as a Compression coat of 5-fluorouracil core tablet for colorectal cancer
Mohammad Zaki Ahmad, Sohail Akhter, Mohammad Anwar, Anjali Singh, Iqbal Ahmad, Ruhul Ain, Gaurav Kumar Jain Roop Krishen Khar and Farhan Jalees Ahmad
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00046]


Floating microspheres - To prolong the gastric retention time in stomach
Priyanka Bhadouriya, Manish Kumar and Kamla Pathak
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00047]


Dual Controlled Release, In Situ Gelling Periodontal Sol Of Metronidazole Benzoate And Serratiopeptidase: Statistical Optimization And Mechanistic Evaluation
Neeraj Kumari and Kamla Pathak
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00048]


Novel Penetration Enhancers for Skin Applications: A Review
Rabinarayan Parhi, Sumant Mondal and Posa Mahesh Kumar
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00049]


Preparation and characterization of poly(2-hydroxyethyl methacrylateco- Methyl methacrylate) hydrogels for sustained delivery of antitumor Drug
Madhu babu. D, satish c. S, ankur p shah and shivakumar h. G
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00050]


Preparation and Characterization of Spray-dried Mucoadhesive Microspheres of Ketorolac for Nasal Administration
C D Nagda, N P Chotai, D C Nagda, S B Patel and U L Patel
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00051]


Natural Oils as Skin Permeation Enhancers for Transdermal Delivery of Olanzapine: In vitro and In vivo Evaluation
Geeta Aggarwal, Sanju Dhawan and S. L. HariKumar
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00052]


Natural Killer cells preferentially target cancer stem cells; Role of monocytes in protection against NK cell mediated lysis of cancer stem cells
Anahid Jewett, Han-Ching Tseng, Aida Arasteh, Saba Saddat, Russell E. Christensen and Nicholas A. Cacalano
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00053]


Molecular Targeted Therapy In Melanoma: A Way To Reverse Resistance To Conventional Drugs
Francesca Maira, Alessia Catania, Saverio Candido, Alessia Erika Russo, James A. McCubrey, Massimo Libra, Grazia Malaponte and Concettina Fenga
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00054]


Novel approaches to modulate apoptosis resistance: basic and clinical implications in the treatment of chronic lymphocytic leukemia (CLL)
Aisha Masood, Mohammad A Shahshahan and Ali R Jazirehi
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00055]


Clinical Use of Rituximab in Patients with HIV Related Lymphoma and Multicentric Castleman’s Disease
Erin Reid, Ajay Nooka, Jawaunna Blackmon and Mary Jo Lechowicz
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00056]


Development and Characterization of Self-nanoemulsifying Drug Delivery Systems (SNEDDS) of Atorvastatin Calcium
Shiva Kumar Mantri, Shailaja Pashikanti and K.V. Ramana Murthy
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00057]


Sustained Ocular Delivery of Brimonidine Tartrate using Ion Activated In Situ Gelling System
A.Geethalakshmi,RoopaKarki, Sajal Kumar Jha, Venkatesh.D.P and B.Nikunj
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00058]


Characterization of the Self Assembly of Methoxy Poly(Ethylene Oxide)-block-Poly(α-Benzyl Carboxylate-ε-Caprolactone) for the Solubilization And In Vivo Delivery of Valspodar
Ziyad Binkhathlan, Sara Elhasi, Dion R. Brocks and Afsaneh Lavasanifar
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00059]


Novel prodrugs for the treatment of colonic diseases based on 5-aminosalicylic acid, 4'-geranyloxyferulic acid, and auraptene: biological activities and analytical assaysFrancesco Epifano, Salvatore Genovese, Giuseppe Carlucci and Marcello Locatelli
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00060]


Delivery methods of camptothecin and its hydrosoluble analogue irinotecan for treatment of colorectal cancer
Adriano Mollica, Azzurra Stefanucci, Federica Feliciani, Ivana Cacciatore, Catia Cornacchia and Francesco Pinnen
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00061]


Natural Products to Improve Quality of Life Targeting for Colon Drug Delivery
Hyunjo Kim
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00062]


Pharmaceutical plasticizers for drug delivery systems
Nashwa A. El-Gendy
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00063]


Rutin-Phospholipid Complex: An Innovative Technique in Novel Drug Delivery System- NDDS
Devendra Singh, M. S. M. Rawat, Ajay Semalty and Mona Semalty
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00064]


Drug Delivery To The Inner Ear: Strategies And Their Therapeutic Implications For Sensorineural Hearing Loss
Teresa Rivera, Lorena Sanz, Guadalupe Camarero and Isabel Varela-Nieto
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00065]


Cyclodextrins as Oral Drug Carrier Molecular Devices: Origins, Reasons and Applications
Dr Roy George, Professor Theunis Oberholzer and Dr V. Tamara Perchyonok
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00066]


A Rational Design For The Nanoencapsulation Of Poisonous Animal Venoms In Liposomes Prepared With Natural Phospholipids
Maria Helena Bueno da Costa, Osvaldo A Sant Anna, Wagner Quintilio, Reto Albert Schwendener and Pedro Soares de Araujo
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00067]


Nanoparticles in the pharmaceutical industry and the use of supercritical fluid technologies for  nanoparticle production
Pratik Sheth, Harpreet Sandhu, Dharmendra Singhal, Waseem Malick, Navnit Shah and M.Serpil. Kislalioglu
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00068]


The use of specific monoclonal antibodies to target Immunogenic tumor membrane proteins in patients with recurrent pancreatic and colon cancer
Myron Arlen, XuePing Wang, Janos Luka, Rishab Gupta, Olga Saric and Philip M. Arlen
[Abstract] [FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00069]



Abstracts


Freeze Dried Chitosan/ Poly-(Glutamic Acid) Microparticles For Intestinal Delivery Of Lansoprazole
Mangla Nand Singh, Hemant KS Yadav, Munshi Ram, Shivakumar H G
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00037]

Lansoprazole sodium is a proton pump inhibitor used in treating gastroesophageal reflux disease (GERD). It is highly acid-labile and presents many formulation challenges. Therefore, this drug need to be protected from the harsh environment in the stomach. In order to achieve this, a pH-sensitive microparticle system composed of chitosan and γ-poly-(glutamic acid) was prepared and loaded with Lansoprazole . The prepared micropartilces were not stable in gastric pH, to overcome this problem microparticles were freeze-dried and filled in an enteric-coated capsule. Upon oral administration, the enteric-coated capsule remained intact in the acidic environment of the stomach, but dissolved rapidly in the distal segment of the GIT. Consequently, all the microparticles loaded in the capsule would be brought into the intestine, thus enhancing the intestinal absorption of drug. Drug encapsulation efficiency of formulation F3 was found to be 82.82 % and in vitro release of prepared formulation F3 was found to be 94% after 8 h of dissolution in 7.4 pH phosphate buffer. FTIR and DSC studies showed no interaction between the drug and polymer. The formulation showed good swelling property. SEM photographs showed that microparticles are spherical and lies in size range of 300-400 μm. From the above, it can be concluded that the prepared chitosan/ γ-poly-(glutamic acid) microparticles can be used as carriers for the intestinal delivery of acid liable drugs such as lansoprazole.
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Microneedles As Transdermal Delivery Systems: Combination With Other Enhancing Strategies
Nava-Arzaluz M.G. Calderón-Lojero I. Quintanar-Guerrero D. Villalobos-García R. Ganem-Quintanar A
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00041]

Transdermal drug delivery has exhaustively been studied over the past decades due to its many advantages over other administration routes; however, drugs that can be administered by this route are few due to the stratum corneum permeability properties. Recently, several strategies to bypass the upper-layer skin barrier have been developed. One of the latest advances in this area has been the use of microscale needles, which painlessly pierce skin, increasing the passage of drugs that have an unfavourable skin permeability (i.e., low potent, hydrophilic, high molecular weight drugs) by several orders of magnitude, bypassing the stratum corneum.

Microneedles have shown to be safe and easy-to-use for drug administration, a novel alternative to hypodermic needle injections, and an array in which drugs can be included to attain a controlled release as to achieve a greater drug delivery.

Several works have demonstrated that such devices dramatically increase transdermal delivery of large molecules. Nowadays microneedles have been regarded as a potential technology approach to be employed alone or with other enhancing methods such as electroporation and iontophoresis, as well as with different drug carriers (e.g., lipid vesicles, micro- and nanoparticles). Hence, this review is mainly focused on presenting the results obtained when combining microneedles with a variety of strategies to facilitate drug diffusion through the skin, including physical enhancers and drug carrier system.
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“Metabolic aspects” in inflammatory bowel diseases
Kaser, M.D.
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00042]

Mesenteric fat hypertrophy is a common feature of inflammatory bowel diseases (IBD), especially Crohn´s disease. Although this “creeping fat” has been observed in the early days of this disease, its biological relevance is not understood. This adipose tissue has been recognized to release large amounts of various cytokines such as TNFα and adipocytokines such as adiponectin or leptin. Whereas leptin is definitely a pro-inflammatory adipocytokine, the role of the prototypic anti-inflammatory adipocytokine, namely adiponectin, in intestinal inflammation is less clear. Some experimental studies suggest that it could exert also pro-inflammatory activities in the gut. An important role for metabolic aspects and potentially adipocytokines has also come from recent studies demonstrating that ATG16L1-deficient mice show a strikingly enhanced expression of both adiponectin and leptin in epithelial cells. Autophagy not only plays a key role in intestinal inflammation, but is also involved in the regulation of lipid metabolism. Another recently identified pathway in IBD, namely endoplasmic stress/XBP1, regulates fatty acid synthesis and facilitates adipogenesis and adipocyte differentiataion. Therefore, XBP1 could possibly link intestinal inflammation with the development of “creeping fat” in Crohn’s disease. Metabolic aspects have evolved as of key importance in experimental colitis and human IBD, and certain adipocytokines, autophagy, and ER stress might reflect the central players. (207 words).
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Foam preparations for the treatment of ulcerative colitis
Burr J. Loew and Corey A. Siegel
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00043]

Patients with ulcerative colitis uniformly have disease involving the distal colon.  When patients have disease limited to the left colon or symptoms suggestive of active rectal inflammation, guidelines recommend topical rectal therapies as first-line agents either as monotherapy or in conjunction with oral products. Rectal delivery modalities offer the advantage of delivering high local concentrations of active medication to the site of maximal inflammation with minimization of systemic side effects.  Methods of rectal administration include suppositories, liquid enemas and foams.  Suppositories are limited to the treatment of rectal disease, and patients often have difficulty retaining the liquid enema secondary to its high volume and consistency.  Rectal foams reliability extend to the descending and sigmoid colon with application.  Foams are further characterized by increased viscosity, lower volumes, finer dispersion on the colonic mucosa, and increased adhesiveness to the colonic mucosa compared with liquid enemas.  Additionally, rectal foam agents demonstrate equal efficacy to their liquid enema counterparts yet consistently yield better patient tolerance, lower incidence of side effects, and increased patient acceptability.  Currently available agents include 5-aminosalicylic acid and corticosteroids, both first and newer generation.  This review focuses on clinical trials assessing efficacy, tolerability, and patient preferences for these agents as well as describing the currently available rectal foam products.
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Cell therapies for inflammatory bowel disease
Julián Panés, Orlando García‐Bosch, Azucena Salas and Daniel Benitez
[Purchase Article] [PMID: 22023203 PubMed - indexed for MEDLINE] [BSP/CDD/E-Pub/00044]

Present therapy of inflammatory bowel diseases (IBD) is aimed at relieving inflammation and treating signs and symptoms. Despite an optimized use of immunosuppressors and the new biologic agents, the need for intestinal resection in Crohn’s disease (CD)has remained stable.1[1] Primary and secondary failure to respond to approved therapies, and in some cases inability to provide a surgical solution to a particular patient due to extension and/or location of lesions, represent unmet needs in the treatment of IBD.

Two streams of research, experimental and clinical, are the origin of the increasing utilization of cell therapies for severe immune‐mediated diseases including IBD, these include stem cell therapies, and selected/conditioned immune cell therapy, such as dendritic and regulatory T cells (Tregs).

Over the last decade, significant responses have been documented to hematopoietic stem cells transplantation (HSCT) in many therapy‐resistant immune‐mediated disorders. Durable remission after immune reconstitution and tissue remodeling suggests an effect beyond profound immunosuppression. Although promising, HSCT for CD is still experimental and its toxicity leaves this option for a considerably reduced number of refractory patients in whom the disease is not amenable to surgical resection. In CD, where loss of tolerance towards commensal bacteria has been invoked in disease development, it would be justified to test the efficacy of tolerance‐promoting cell therapies. Various approaches are being explored and have shown promising results in experimental models of autoimmunity. These include administration of mesenchimal stem cells, Tregs or tolerogenic dendritic cells.
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What is the optimal treatment for anemia in inflammatory bowel disease?
Alexandra J Kent MRCP, Victoria J Blackwell MRCP and Simon PL Travis DPhil FRCP
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00045]

Anemia is common in inflammatory bowel disease (IBD), with a prevalence ranging from 8.8% to 73.7%. This wide range reflects the definitions used and the populations studied. Although many patients are reported to be asymptomatic, systematic studies have shown anemia to have a significant impact on quality of life. Consequently treatment should be instituted early. The commonest cause of anemia in IBD is iron deficiency, predominantly related to gastro-intestinal blood loss. Anemia of chronic disease often occurs concomitantly, due to cytokine-mediated impaired erythropoiesis and dysregulated iron metabolism. Oral iron is a simple and effective method for treating iron deficiency, but requires long courses of treatment. It is also theoretically implicated with worsening intestinal inflammation, via the production of toxic reactive oxygen species. Intravenous iron avoids these concerns, especially with the development of ferric carboxymaltose, which allow up to 1000mg to be given rapidly. In patients failing to respond to intravenous iron, the anemia of chronic disease is most likely to be causative. In this setting evidence suggests that additional erythropoietin therapy can be effective. Blood transfusions should be avoided as part of routine management and reserved for patients with substantial acute gastro-intestinal bleeding, where there is a risk of hemodynamic compromise. This article discusses the underlying physiology of anemia in IBD, and presents the current evidence supporting treatment options available.
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Feasibility of Assam Bora rice starch as a Compression coat of 5-fluorouracil core tablet for colorectal cancer
Mohammad Zaki Ahmad, Sohail Akhter, Mohammad Anwar, Anjali Singh, Iqbal Ahmad, Ruhul Ain, Gaurav Kumar Jain Roop Krishen Khar and Farhan Jalees Ahmad
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00046]

The colon and rectum are the parts of digestive system of human beings. Cancer affecting either of these organs may be called colorectal cancers. Conventional cancer chemotherapy is not very effective for treatment of colorectal cancer, as the drug molecule does not reach the target site at therapeutic concentration, on the other side they produces sever systemic toxic effect. Aim of this study was to develop a novel colon targeted Assam Bora rice starch compression coated tablet for site specific delivery of 5-FU to the colon without the drug being released in stomach or small intestine. Core tablet of 5-FU was prepared using microcrystalline cellulose (MCC) and spray dried lactose by direct compression method. The in vitro drug release study in different physiological environment confirmed insignificant release of 5-FU in physiological condition of stomach and small intestine further fast and major drug release in caecal content. In vivo drug absorption of optimized formulation was performed in order to establish its targeting potential in colon. It is concluded from the present study that Assam Bora rice starch can be used as a drug carrier for an effective colon targeted delivery system for drugs effective against the large intestine resident disease condition.
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Floating microspheres - To prolong the gastric retention time in stomach
Priyanka Bhadouriya, Manish Kumar and Kamla Pathak
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00047]

A gastroretentive drug delivery system with prolong retention time in the stomach have great practical importance for drugs with an absorption window in the upper small intestine. Floating drug delivery system are expected to remain buoyant in the gastric content for prolong duration of time thus enhance the bioavailability of drugs. There are several gastroretentive drug delivery systems, which are floating microspheres, granules, tablets, powder, pills, laminated films and capsules. Floating microspheres are gaining special attention because of their wide applicability in the targeting of drug to stomach. Floating microspheres have several advantages, that they remain buoyant in the stomach and distributed uniformly to avoid the vagaries of gastric emptying and release the drug for prolong period of time.
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Dual Controlled Release, In Situ Gelling Periodontal Sol Of Metronidazole Benzoate And Serratiopeptidase: Statistical Optimization And Mechanistic Evaluation
Neeraj Kumari and Kamla Pathak
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00048]

In situ gelling  syringeable periodontal sol capable of  dual controlled delivery of  metronidazole benzoate and serratiopeptidase were designed  based on 2³ factorial design  with  drug, poloxamer 407 and aerosil as independent variables and sol gel transition characteristics, %CDR_48h and palatability as responses. The sols had agreeable taste, were mucoadhesive, syringeable and inverted into gels at periodontal cavity temperature. F8 with optimal drug release was identified as the best formulation.  The dispersion characteristics of poloxamer significantly affected the pharmacotechnical properties of the in situ gelling systems. Extra design checkpoint generated using Design Expert software 8.02 (Stat-Ease, USA) validated the experimental design. Thus a thermoreversible, in situ gelling and syringeable periodontal sol with acceptable taste characteristics that offered controlled release of metronidazole benzoate and serratiopeptidase was developed for application into the periodontal pocket. The developed optimized sol was satisfactory in terms of taste, syringeability, palatability and incorporation of serratiopeptidase as anti-inflammatory agent, has the potential of developing a therapeutically efficacious system for treatment of periodontal inflammatory anaerobic infections.
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Novel Penetration Enhancers for Skin Applications: A Review
Rabinarayan Parhi, Sumant Mondal and Posa Mahesh Kumar
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00049]

The use of topical formulation is popular over the past decade due to extensive researches have been made in the field of transedermal drug delivery. As a result an increasing number of drugs are being added to the list of therapeutic agents that can be delivered to systemic circulation through the skin. Commonly available dosage forms for the topical application are creams, ointments, gels, patches etc. The therapeutic benefits of the above topical formulations are limited due to barrier property of stratum corneum (SC). The use of chemical penetration enhancers (CPEs) is one of the long standing approach to overcome the barrier property of SC. Numerous class of novel compounds have been evaluated for penetration enhancement activity, including soft enhancement for percutaneous absorption (SEPA), where soft indicates that the absorption enhancement is temporary and reversible due to rapid breakdown of the enhancer, for example, 2 N-nonyl-1,3-dioxolanes, N-acetyle prolinate esters (such as pentyl- and octyl-N-acetyle prolinate), alkyldiloxanes (e.g., 1-Alkyl-3-b-D glucopyranosyl-1,1,3,3-tetramethyl disiloxanes), transcarbam (such as 5-(dodecyloxycarbonyl) pentylammonium-5-(dodecyloxycarbonyl) pentylcarbamate), iminosulfurane (like N-hexyl,N-benzoyl-S,S-dimethylimino-sulfuranes), capsaicin derivatives (e.g., Nonivamide), cinnamene compounds (such as cinnamic acid, cinnamaldehyde etc), terpenes (like clove and basil oil) and synergestic combination of penetration enhancers (SCOPE). We briefly describe about the anatomy of skin. Potential mechanisms of action of above novel PEs along with adverse reactions associated with traditional PEs are also considered in this review.
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Preparation and characterization of poly(2-hydroxyethyl methacrylateco- Methyl methacrylate) hydrogels for sustained delivery of antitumor Drug
Madhu babu. D, satish c. S, ankur p shah and shivakumar h. G
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00050]

The aim of this study was to prepare different types of cisplatin loaded poly(HEMA-co-MMA) hydrogel based implants. These systems are designed to release the drug in a time-controlled manner over several weeks which can help in optimizing the treatment of tumors. The prepared implants were evaluated for swellability, in vitro and in vivo release and biodegradation studies. Swelling studies of the implants were carried out in 7.4 pH phosphate buffer solution and swelling was to depend on the extent of cross-linking. From the results of in vitro release studies it was observed that, the diffusion coefficient of cisplatin in the early stages was in the range of 4.3× 10-6 to 8.0 ×10-6 cm2 min-1 and at later stages it was found to be in the range of 3.2 × 10-8 to 6.0 ×10-8 cm2 min-1. The results of the in vivo drug release revealed that the drug release was faster in vivo compared to the in vitro release for the corresponding formulations. The in vivo studies showed that cisplatin was released for a period of 20 days and also there was no fibrous capsule formation around the implant indicating the biocompatibility of the implant.
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Preparation and Characterization of Spray-dried Mucoadhesive Microspheres of Ketorolac for Nasal Administration
C D Nagda, N P Chotai, D C Nagda, S B Patel and U L Patel
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00051]

The objective of this investigation was to prepare mucoadhesive microspheres of ketorolac for nasal delivery to avoid gastrointestinal side effects of conventional dosage form. Mucoadhesive microspheres were prepared using carbopol, polycarbophil and chitosan as polymer by spray drying method. The process and formulation parameters were varied to study the effect on the yield and particle size. Microspheres were characterized for surface morphology, encapsulation efficiency, swelling behavior, mucoahesion properties, interaction studies using FTIR and DSC, in vitro drug release, ex vivo nasal cilio toxicity studies and in vivo anti-inflammatory and analgesic activity. Prepared microspheres were discrete, bulky, free flowing and showed an average encapsulation efficiency ranging from 79-92%. The results showed that the process parameters significantly affect the particle size (10.29-16.75 μm) and yield of microspheres (36.53-56.69%). Interaction studies revealed that there was no drug to polymer interactions. Prepared microspheres exhibited good swelling and mucoadhesion strength which confined the strong mucoadhesive property of microspheres. Ketorolac release from the microspheres was extended up to 8 h and exhibited fickian drug release kinetics with best fit to higuchi model. The drug loaded microspheres were found to be nontoxic to nasal mucosa. The anti-inflammatory and analgesic effects of formulation showed a significant increase (p < 0.05) in percent inhibition value up to 8 h when compared with ketorolac. In conclusion, spray dried microspheres based on chitosan could be suitable nasal delivery system for the administration of ketorolac.
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Natural Oils as Skin Permeation Enhancers for Transdermal Delivery of Olanzapine: In vitro and In vivo Evaluation
Geeta Aggarwal, Sanju Dhawan and S. L. HariKumar
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00052]

The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm²/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.
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Natural Killer cells preferentially target cancer stem cells; Role of monocytes in protection against NK cell mediated lysis of cancer stem cells
Anahid Jewett, Han-Ching Tseng, Aida Arasteh, Saba Saddat, Russell E. Christensen and Nicholas A. Cacalano
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00053]

Mounting effective anti-tumor immune responses by cytotoxic effectors is important for the clearance of tumors. However, accumulated evidence suggests that the cytotoxic function of immune effectors is largely suppressed in the tumor microenvironment by a number of distinct effectors and their secreted factors. The aims of this review are to provide a rationale and potential mechanism for immunosuppression in cancer, and to demonstrate the significance of such immunosuppression in cellular differentiation and tissue regeneration in pathological conditions, and progression of cancer. We have recently shown that increased NK cell function was seen when they were cultured with primary oral squamous carcinoma stem cells (OSCSCs) as compared to their more differentiated oral squamous carcinoma cells (OSCCs). In addition, human embryonic stem cells (hESCs), Mesenchymal Stem Cells (hMSCs), dental pulp stem cells (hDPSCs) and induced pluripotent stem cells (hiPSCs) were significantly more susceptible to NK cell mediated cytotoxicity than their differentiated counterparts or parental cells from which they were derived. We have also reported that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 augmented NK cell function significantly. Total population of monocytes and those depleted of CD16(+) subsets were able to substantially prevent NK cell mediated lysis of OSCSCs, MSCs and DPSCs. Taken together, our results suggest that stem cells are significant targets of the NK cell cytotoxicity. The concept of split anergy in NK cells and its contribution to tissue repair and regeneration and in tumor resistance and progression will be discussed in this review. Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation at the site of the tumor for specific elimination of cancer stem cells.
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Molecular Targeted Therapy In Melanoma: A Way To Reverse Resistance To Conventional Drugs
Francesca Maira, Alessia Catania, Saverio Candido, Alessia Erika Russo, James A. McCubrey, Massimo Libra, Grazia Malaponte and Concettina Fenga
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00054]

Cutaneous melanoma is the most aggressive skin cancer. Beside surgery, it is treated with chemotherapy and immunotherapy. However, many patients relapse after adjuvant therapy. The recent identification of several key molecular pathways implicated in the pathogenesis of melanoma is spreading development of a number of new  translational targeted therapies which could play an important role in overcoming or minimizing resistance to chemotherapeutic drugs and proapoptotic therapies. This review summarizes environmental factors and the most significant molecular events involved in melanoma pathogenesis, disclosing mechanisms responsible for drug resistance and pointing out the clinical view for emerging targeted therapies. Standard therapies and an update on the current clinical trials are also described.
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Novel approaches to modulate apoptosis resistance: basic and clinical implications in the treatment of chronic lymphocytic leukemia (CLL)
Aisha Masood, Mohammad A Shahshahan and Ali R Jazirehi
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00055]

Chronic lymphocytic leukemia (CLL) is an archetype of malignancy resulting from defects in apoptosis.  CLL is an exclusive accumulative disorder marked by low proliferative activity and gradual accumulation of clonal B-lymphocytes blocked in the early (G0, G1) phases of the cell cycle.  The heterogeneous clinical course indicates diverse in vivo biology of the leukemic cell and suggests that CLL represents diverse behavior. Understanding the molecular biology of the disease has provided insight into the mechanisms that promote tumorigenesis, specifically defective apoptotic signaling pathways. In this review we attempt to provide a comprehensive discussion of CLL including the origin of malignant lymphocytes, the apoptotic defects and the mechanisms leading to disease progression. We further discuss the therapeutic options, focusing mainly on targeted therapy using novel agents.  Finally, we suggest future directions for treatment that utilize the understanding of the disease biology.
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Clinical Use of Rituximab in Patients with HIV Related Lymphoma and Multicentric Castleman’s Disease
Erin Reid, Ajay Nooka, Jawaunna Blackmon and Mary Jo Lechowicz
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00056]

The use of immunotherapy in the treatment of non-Hodgkin lymphomas has improved response rates and survival in this population.  With widespread rituximab use and longer-term follow-up of patients receiving rituximab, infectious complications are increasing.  These complications are of great concern in the AIDS-related lymphoma population.  We review the data on activity and infectious toxicity of rituximab to date and as it pertains to the treatment of AIDS-related non-Hodgkin lymphoma and Multicentric Castleman’s disease.
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Development and Characterization of Self-nanoemulsifying Drug Delivery Systems (SNEDDS) of Atorvastatin Calcium
Shiva Kumar Mantri, Shailaja Pashikanti and K.V. Ramana Murthy
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00057]

The main aim of the present investigation is to develop and characterize the self-nanoemulsifying drug delivery systems (SNEDDS) of atorvastatin calcium (ATV) for improving the dissolution thereby oral bioavailability and to minimize the gastric degradation. Naturally occurring different vegetable oils, various surfactants and co-surfactants were studied for ATV solubility to identify the components of SNEDDS. Ternary phase diagrams comprising surfactant, co-surfactant and oil were plotted. In the ternary phase diagrams the area of self-nanoemulsifying region was marked for the compositions that are giving dispersion with a globule size ≤200 nm. Effect of drug loading on the phase behavior of selected system was studied. A series of SNEDDS were prepared by selecting from the nanoemulsifying area of 2.5% ATV system. Prepared SNEDDS were evaluated for visual observations, turbidity, effect of pH of the dispersion media on globule size and zeta potential, robustness to dilution and in vitro dissolution study and optimized. FT-IR and DSC were studied for interaction between drug and excipients if any. Forced degradation and accelerated stability studies were conducted for optimized SNEDDS. ATVF 04 and 11 were selected as optimized SNEDDS due to their smaller mean globule size (75.2 and 85.8 nm respectively), lower turbidity values, faster drug release and higher DE values among the other SNEDDS. The optimized ATV SNEDDS were not affected by the pH of dilution medium. FT-IR study revealed no interaction between drug and excipients used. Forced degradation studies indicated the stability of ATV in the gastric environment. Accelerated stability studies showed no significant changes in the mean globule size, zeta potential, drug content and drug release before and after storage of optimized SNEDDS.
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Sustained Ocular Delivery of Brimonidine Tartrate using Ion Activated In Situ Gelling System
A.Geethalakshmi,RoopaKarki, Sajal Kumar Jha, Venkatesh.D.P and B.Nikunj
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00058]

The poor bioavailability and therapeutic response exhibited by conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of an in situ gelling systems that are instilled as drops into the eye and undergo a sol-to-gel transition in the cul-de-sac which improves patient compliance as the dosage regimen is one drop of the dosage form twice a day. The loss of drug is overcome due to the immediate gel formation between the eye membrane and the drug getting entrapped simultaneously in sol–gel transition in the cul de sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antiglaucomal agent, brimonidine tartrate based on the concept of ion-activated in situ gelation. Gelrite was used as the gelling agent, which gels in the presence of mono or divalent cations present in the lacrimal fluid. The formulations were evaluated for clarity, pH measurement, gelling capacity, drug content estimation, rheological study, in-vitro diffusion study, antibacterial activity, isotonicity testing, eye irritation testing. In the developed formulations Gelrite Brimonidine-3 (GB3) exhibited sustained release of drug from formulation over a period of 8hrs thus increasing residence time of the drug, non-irritating with no ocular damage or abnormal clinical signs to the cornea, iris or conjunctiva, stable and sterile. These results demonstrate that the developed system is an alternative to conventional ophthalmic drops, better patient compliance, industrially oriented and economical.
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Characterization of the Self Assembly of Methoxy Poly(Ethylene Oxide)-block-Poly(α-Benzyl Carboxylate-ε-Caprolactone) for the Solubilization And In Vivo Delivery of Valspodar
Ziyad Binkhathlan, Sara Elhasi, Dion R. Brocks and Afsaneh Lavasanifar
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00059]

The aim of this study was to characterize the nanostructures formed from assembly of poly(ethylene oxide)-b-poly(α-benzyl carboxylate ε-caprolactone) (PEO-b-PBCL) in water, determine the effect of weight fraction of the hydrophilic block(f_EO) on the their morphology, and to investigate their potential for solubilization and delivery of P-glycoprotein (P-gp) inhibitor, valspodar. Three PEO-b-PBCL block copolymers having f_EO ranging from 0.18-0.40 were synthesized. Assembly of PEO-b-PBCL was triggered through a co-solvent evaporation method. The average critical aggregation concentration (CAC) for PEO₁₁₄-b-PBCL₃₀, PEO₁₁₄-b-PBCL₆₀, and PEO₁₁₄-b-PBCL₉₅ was found to be 62, 41, and 23 nM, respectively. A lower rigidity of the hydrophobic domain in nanostructures formed from the assembly of PEO₁₁₄-b-PBCL₆₀ and PEO₁₁₄-b-PBCL₉₅ in comparison to PEO₁₁₄-b-PBCL30 was observed. The morphology of the assembled structures was characterized by transmission electron microscopy (TEM). The TEM images of PEO₁₁₄-b-PBCL₃₀ (f_EO = 0.40) showed the formation of spherical micelles with high polydispersity, whereas the assembly of PEO₁₁₄-b-PBCL₆₀ (f_EO = 0.25) and PEO₁₁₄-b-PBCL₉₅ (f_EO = 0.18) resulted in a mixed population of spherical micelles and vesicles. Valspodar achieved high loading in all the three PEO-b-PBCL nanocarriers reaching aqueous solubility of nearly 2 mg/mL. The morphology of PEO-b-PBCL carrier did not seem to influence the pharmacokinetics of the encapsulated valspodar in rats following intravenous administration. In conclusion, the results show a potential for PEO-b-PBCL nanocarriers as efficient solubilizing agents for delivery of valspodar.
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Novel prodrugs for the treatment of colonic diseases based on 5-aminosalicylic acid, 4'-geranyloxyferulic acid, and auraptene: biological activities and analytical assaysFrancesco Epifano, Salvatore Genovese, Giuseppe Carlucci and Marcello Locatelli
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00060]

A pro-drug is a substance administered in a pharmacologically inactive structure that, once administered, is metabolised in vivo into the corresponding active principle. The rationale for the design of prodrugs is the optimisation of absorption, distribution, metabolism, and excretion (ADME). Moreover these compounds are frequently synthesized to improve bioavailability. 5-Amino salicylic acid (5-ASA) represents one of the most efficient agents for ColoRectal Cancer (CRC) treatment. Its inclusion in natural or semi-synthetic cyclodextrins (CDs) has been extensively studied to enhance drug properties as solubility, stability, and bioavailability. On the other hand, very recently naturally occurring 4'-geranyloxyferulic acid and auraptene were found as novel promising agents for the treatment of colon diseases, like adenomas and adenocarcinomas. In this review we will focus our attention on the reported pharmacological activity and analytical assays for the most representatives 5-ASA pro-drugs already in therapy for treatment of CRC and on novel prodrugs of 4’-geranyloxyferulic acid and auraptene that were shown to be efficient in vivo as dietary feeding colon cancer chemopreventers in mice.
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Delivery methods of camptothecin and its hydrosoluble analogue irinotecan for treatment of colorectal cancer
Adriano Mollica, Azzurra Stefanucci, Federica Feliciani, Ivana Cacciatore, Catia Cornacchia and Francesco Pinnen
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00061]

Camptothecins are a family of alkaloids originally extracted from the Chinese tree Camptotheca acuminata, Nyssaceae, exhibiting a strong activity against colorectal cancer (CRC). CRC is a common malignancy worlwide. Despite significant developments in the treatment of this disease, it still causes considerable morbidity and mortality.  Recent advances include both newer cytotoxic chemotherapies and novel biological agents including the more hydrosoluble camptothecin derivative, namely irinotecan. Camptothecin and irinotecan are selective human topoisomerase I inhibitors but their application for curing CRC is compromised by their intrinsic high toxicity, insolubility and instability. Furthermore, pharmacology studies have determined that continuously and prolonged schedules of administration are required. The aim of this work is to review the state of the art of camptothecin and its derivative irinotecan’s delivery methods.
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Natural Products to Improve Quality of Life Targeting for Colon Drug Delivery
Hyunjo Kim
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00062]

The colon is largely being investigated as a site for administration of protein and peptides, which are degraded by digestive enzymes in the upper GIT. Also for local diseases of the colon such as inflammatory bowel disease, colorectal cancer and ameobiasis, drug administration to the site of action can not only reduce the dose to be administered, but also decrease the side effects.

Inflammatory Bowel Disease (IBD) such as Ulcerative colitis and Crohn's disease are characterized by chronic intestinal inflammation. Intestinal bacteria initiate the activation of intestinal inflammatory processes, which are mediated by pro-inflammatory cytokines and chemokine.

Increased chemokine expression has also been observed in epithelial cells, endothelial cells, and smooth muscle cells. Future trials of specific agents capable of inhibiting chemokine synthesis and secretion or blocking chemokine-chemokine receptor interaction will be important to study in patients with ulcerative colitis and Crohn's disease.

Many important bioactive compounds have been discovered from natural sources using bioactivity directed fractionation and isolation (BDFl) Continuing discovery has also been facilitated by the recent development of new bioassay methods. These bioactive compounds are mostly plant secondary metabolites, and many naturally occurring pure compounds have become medicines, dietary supplements, and other useful commercial products.

The present review includes various approaches investigated for colon drug delivery and their site specificity. To achieve successful colonic delivery, a drug needs to be protected from absorption and the environment of the upper gastrointestinal tract and then be abruptly released into the proximal colon, which is considered the optimum site for colon targeted delivery of drugs.
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Pharmaceutical plasticizers for drug delivery systems
Nashwa A. El-Gendy
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00063]

In the field of pharmaceutical science and drug development, there is an important and particular challenges related to the selection of suitable and compatible ingredients as well as the design of successful formulations. As plasticization is a phenomenon widely exploited in all formulation fields, plasticizers should be recognized as a critical aspect for drug delivery. The choice of an appropriate plasticizer requires a wide background of information. This is because they are incorporated into drug delivery systems containing an assortment of ingredients which may have different reactions to the presence of plasticizers. Concurrently, there are numerous pharmaceutical plasticizers and various environmental issues dictating favored solutions. To address these encumbrances, an extensive information concerning plasticizers; their types, properties, pharmaceutical roles, etc. is discussed. Additionally, the specific objective of this review is to substantiate the safety and performance of newly discovered plasticizers.
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Rutin-Phospholipid Complex: An Innovative Technique in Novel Drug Delivery System- NDDS
Devendra Singh, M. S. M. Rawat, Ajay Semalty and Mona Semalty
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00064]

Biopharmaceutical properties together with potency contribute critically towards clinical efficacy of the drugs by influencing the dissolution and bioavailability. The aim of this study was to develop an amphiphilic phyto-phospholipid complex in order to enhance the delivery of rutin due to poor solubility and hence the dissolution. The rutin-phospholipid complex (Ru-PLc) was prepared and investigated for various physico-chemical parameters like drug loading, infrared absorption (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), aqueous/ n-octanol solubility and dissolution study. The in vitro anti-oxidant activity was also studied. In the SEM, Ru-PLc was found fluffy and porous with rough surface morphology. FTIR, DSC and XRPD data confirmed the formation of phospholipid complex. The water/ n-octanol solubility of rutin was improved from 2.88 to 45.71 μg/ ml and 68.17 to 245.18 μg/ ml, respectively in the prepared complex. The improved dissolution was shown by the phospholipid complex at different pH buffers. The antioxidant activity indicated that, the bioactivity of rutin was maintained after complexed with the phospholipid. Based on the results, it can be concluded that the phospholipid complex may be considered as promising drug delivery system for improving the overall absorption and bioavailability of the rutin molecule.
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Drug Delivery To The Inner Ear: Strategies And Their Therapeutic Implications For Sensorineural Hearing Loss
Teresa Rivera, Lorena Sanz, Guadalupe Camarero and Isabel Varela-Nieto
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00065]

Hearing aids or cochlear implants constitute almost exclusively the treatment options currently available to patients suffering from sensorineural hearing loss and related conditions, such as noise-induced hearing loss, ototoxicity or autoimmune inner ear disease. While some systemic treatments exist, they generally exert adverse secondary effects and their efficacy is hampered by the blood-cochlear barrier that limits drug access to the inner ear. Hence, the new therapies that are being developed for hearing loss focus on strategies for direct drug delivery to the inner ear. The passive and active methods for local delivery can be categorized into two general groups: intratympanic or intracochlear. The intratympanic approach is a non-invasive method that preserves hearing and takes advantage of the permeability of the round window to gain access to the cochlea. However, this technique is limited by not knowing the dose of the drug that reaches the cochlea, (a handicap whichmight be overcome by the use of tagged drugs). While direct access to the inner ear by intracochlear administration avoids this problem, this method requires surgery. Currently, laboratory animals are being used to explore which therapeutic approaches are best suited to address this problem. These include cochleostomy and the insertion of devices that pump drugs into the inner ear without inducing cochlear damage. In this article, we review the different techniques under evaluation in animal models of deafness, and their potential use for drug delivery and treatment of human inner ear diseases.
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Cyclodextrins as Oral Drug Carrier Molecular Devices: Origins, Reasons and Applications
Dr Roy George, Professor Theunis Oberholzer and Dr V. Tamara Perchyonok
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00066]

Cyclodextrins are a family of cyclic oligosaccharides composed of a (1,4) linked glucopyranose subunits. Cyclodextrins are useful molecular chelating agents. They possess a cage-like supramolecular structure, which is the same as the structures formed from cryptands, calixarenes, cyclophanes, spherands and crown ethers. These compounds having supramolecular structures carry out chemical reactions that involve intramolecular interactions where covalent bonds are not formed between interacting molecules, ions or radicals. The majority of all these reactions are of ‘host–guest’ type. Compared to all the supramolecular hosts mentioned above, cyclodextrins are most important.

Because of their inclusion complex forming capability, the properties of the materials with which they complex can be modified significantly. The cyclodextrins have a wide range of applications in different areas of drug delivery and pharmaceutical industry due to their complexation ability and other versatile characteristics. The most common pharmaceutical application of cyclodextrin is to enhance the solubility, stability, safety and bioavailability of drug molecules. The purpose of this review is to discuss and summarize some of the findings and applications of cyclodextrin (CD) and their derivatives in different areas of drug delivery. This article highlights the molecular structure, properties like complexation, solubility etc. of cyclodextrins and focuses on its use for oral drug delivery. The objective of this contribution is to focus on the potential use of chemically modified cyclodextrins as high performance drug carriers in drug delivery systems with emphasis on the more recent developments. Thus cyclodextrins, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes.
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A Rational Design For The Nanoencapsulation Of Poisonous Animal Venoms In Liposomes Prepared With Natural Phospholipids
Maria Helena Bueno da Costa, Osvaldo A Sant Anna, Wagner Quintilio, Reto Albert Schwendener and Pedro Soares de Araujo
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00067]

Liposomes have been used since the 1970’s to encapsulate drugs envisaging enhancement in efficacy and therapeutic index, avoidance of side effects and increase in the encapsulated agent stability. The major problem when encapsulating snake venoms is the liposomal membrane instability caused by venom phospholipases. Here the results obtained encapsulating Crotalus durissimus terrificus and a pool of Bothropic venoms within liposomes (LC and LB, respectively) used to produce anti-venom sera are presented. The strategy was to modify the immunization protocol to enhance antibody production and to minimize toxic effects by encapsulating inactivated venoms within stabilized liposomes. Chemically modified venoms were solubilised in a buffer containing an inhibitor and a chelating agent. The structures of the venoms were analysed by UV, CD spectroscopy and ELISA. In spite of the differences in the helical content between natural and modified venoms, they were recognized by horse anti-sera. To maintain long-term stability, mannitol was used as a cryoprotectant. The encapsulation efficiencies were 59 % (LB) and 99 % (LC), as followed by filtration on Sephacryl S1000. Light scattering measurements led us to conclude that both, LB (119 ±47 nm) and LC (147±56 nm) were stable for 22 days at 4 °C , even after lyophilization. Genetically selected mice and mixed breed horses were immunized with these formulations. The animals did not show clinical symptoms of venom toxicity. Both, LB and LC enhanced by at least 30 % the antibody titers 25 days after injection and total IgG titers remained high 91 days after immunization. The liposomal formulation clearly exhibited adjuvant properties.
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Nanoparticles in the pharmaceutical industry and the use of supercritical fluid technologies for  nanoparticle production
Pratik Sheth, Harpreet Sandhu, Dharmendra Singhal, Waseem Malick, Navnit Shah and M.Serpil. Kislalioglu
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00068]

Poor aqueous solubility of drug candidates is a major challenge for the pharmaceutical scientists involved in drug development. Particle size reduction appears as an effective and versatile option for solubility improvement. Nanonization is an attractive solution to improve the bioavailability of the poorly soluble drugs, improved therapies, in vivo imaging, in vitro diagnostics and for the production of biomaterials and active implants.

In drug delivery, application of nanotechnology is commonly referred to as Nano Drug Delivery Systems (NDDS). In this article, commercially available nanosized drugs, their dosage forms and proprietors, as well as the methods used for preparation like milling, high pressure homogenization, vacuum deposition, and high temperature evaporation were listed. Unlike the traditional methods used for the particle size reduction, supercritical fluid-processing techniques offer advantages ranging from superior particle size control to clean processing.  

The primary focus of this review article is the use of supercritical CO₂ based technologies for small particle generation.  Particles that have the smooth surfaces, small particle size and distribution and free flowing can be obtained with particular SCF techniques.  In almost all techniques, the dominating process variables may be thermodynamic and aerodynamic in nature, and the design of the particle collection environment. 

Rapid Expansion of Supercritical Solutions (RESS), Supercritical Anti Solvent (SAS) and Particles from Gas Saturated Solutions (PGSS) are three groups of processes which lead to the production of fine and monodisperse powders. Few of them may also control crystal polymorphism.   Among the aforementioned processes, RESS involves dissolving a drug in a supercritical fluid (SCF) and passing it through an appropriate nozzle. Rapid depressurization of this solution causes an extremely rapid nucleation of the product. This process has been known for a long time but its application is limited. Carbon dioxide, which is the only supercritical fluid that is preferentially used in pharmaceutical processes, is not a good solvent for many Active Pharmaceutical Ingredients (API). Various researchers have modified the RESS process to overcome its solubilizing limitations, by introducing RESOLV, RESAS, and RESS-SC.  Overall, all RESS based processes are difficult to scale up.  

 The SAS processes are based on decreasing the solvent power of a polar organic solvent in which the substrate (API & polymer of interest) is dissolved, by saturating it with carbon dioxide (CO₂) at supercritical conditions. CO₂ causes precipitation and recrystalization of the drug. SAS is scalable and can be applied to a wide variety of APIs and polymers. Minor modifications of basic SAS process include GAS, ASES, SAS-DEM and SAS-EM. Processes where SCF is used as an anti solvent and dispersing agent include SEDS, SAA, and A-SAIS. The mechanisms and applications of these processes were briefly discussed.   In PGSS, CO₂ is dissolved in organic solutions or melted compounds and it is successfully used for manufacturing drug products as well as for drying purposes. The two widely used methods, PGSS-drying and CAN-BD SCF, were also included in discussions.

Among the limitations of the techniques involved, the poor solvent power of CO₂, the cost and necessity of voluminous usage of the CO₂ can be mentioned. There is still confusion in contribution of each variable on the particle morphology and properties regardless of the number of mechanistic studies available.  The advantages of especially SAS and PGSS based techniques are the production of the nano or micro sized spherical particles with smooth surfaces and narrow particle size distribution. Regardless of its advantages, the reasons why 25 years of active research, and more than 10 years of process development could not promote the use of (SCF) technology, and produced only few commercial drug products, necessitate further evaluation of this technique.
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The use of specific monoclonal antibodies to target Immunogenic tumor membrane proteins in patients with recurrent pancreatic and colon cancer
Myron Arlen, XuePing Wang, Janos Luka, Rishab Gupta, Olga Saric and Philip M. Arlen
[FULL-TEXT INQUIRY] [BSP/CDD/E-Pub/00069]

Tumor associated antigens from pooled allogeneic membrane proteins were isolated, partially purified and tested as a possible vaccine in patients with stage II and III colon cancer. The vaccine, when given in combination with an adjuvant following surgical resection, resulted in marked improvement in survival compared to control patients having only undergone surgical resection of their tumor.   While it was possible to demonstrate that patients receiving vaccine turned on both humoral and cell mediated responses, it appears that survivors remaining free of disease at 5-7 yrs post op were able to mount a strong IgG1 response as the primary mechanism for tumor destruction. Antibodies from hybridomas made against the vaccines resulted in production of monoclonals with a high degree of ADCC.  Those monoclonals targeting pancreatic cancer and in particular the MUC5ac mutated antigen representing tumor immunogen were studied in detail.  Animal models indicated rapid tumor destruction when nude mice, injected with human pancreatic cancer were then immunized with  NPC-1 monoclonal antibody targeting mutated MUC5ac.  FDA studies including tissue cross reactivity, biodistribution, and cytokine release assays indicated safety and efficacy of the monoclonals we have developed.  Submission of the IND allowed for initiation of the Phase I trial using mAb NPC-1 targeting pancreatic cancer when that antigen was found to be expressed. 
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