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Current
Drug Delivery
ISSN: 1567-2018
Current Drug Delivery
Volume 7, Number 4,
October 2010
Contents
Magnetically Responsive Paclitaxel-Loaded
Biodegradable Nanoparticles for Treatment of Vascular Disease:
Preparation, Characterization and In Vitro Evaluation
of Anti-Proliferative Potential Pp. 263-273
Brandon Johnson, Brent Toland, Rishi Chokshi,
Vadym Mochalin, Sirma Koutzaki and Boris Polyak
[Abstract] [Purchase
Article]
Phosphodiesterase-5 Inhibitor Tadalafil Acts on
Endothelial Progenitor Cells by CXCR4 Signalling
Pp. 274-282
Carlo Foresta, Luca De Toni, Sabina Magagna, Alessandro Galan
and Andrea Garolla
[Abstract] [Purchase
Article]
Topical Dermatological Drug Delivery: Quo Vadis?
Pp. 283-296
Franklin K. Akomeah
[Abstract] [Purchase
Article]
Release of Antithrombotic Drugs from Alginate
Gel Beads Pp. 297-302
Erik Jämstorp, Aase Bodin, Paul Gatenholm, Anders Jeppsson
and Maria Strømme
[Abstract] [Purchase
Article]
Nanoparticles: A Promising Therapeutic Approach
in Atherosclerosis Pp. 303-311
Charalambos Antoniades, Costantinos Psarros, Dimitris
Tousoulis, Constantinos Bakogiannis, Cheerag Shirodaria and
Christodoulos Stefanadis
[Abstract] [Purchase
Article]
Chloroquine Resistance: Proposed Mechanisms and
Countermeasures Pp. 312-323
Eric Guantai and Kelly Chibale
[Abstract] [Purchase
Article]
Evaluation of Extemporaneously Manufactured Topical
Gels Containing Aceclofenac on Inflammation and Hyperalgesia
in Rats Pp. 324-328
Kavita Pabreja, Kamal Dua and Satyanaryana
S.V. Padi
[Abstract] [Purchase
Article]
Effect of Iontophoresis and Permeation Enhancers
on the Permeation of an Acyclovir Gel Pp. 329-333
Subhash S. Vaghani, Mitesh Gurjar, Sachin Singh, Sunil
Sureja, Shailesh Koradia, N.P. Jivani and M.M. Patel
[Abstract] [Purchase
Article]
Utilization of Hydrophilic Swellable Polymers
as Carriers for Sustained Drug Delivery from Matrices and
three Layer Tablet Systems Pp. 334-342
Marilena Vlachou, Hani Naseef and Manuel
Efentakis
[Abstract] [Purchase
Article]
Abstracts
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Magnetically Responsive Paclitaxel-Loaded Biodegradable
Nanoparticles for Treatment of Vascular Disease: Preparation,
Characterization and In Vitro Evaluation of Anti-Proliferative
Potential
Brandon Johnson, Brent Toland, Rishi Chokshi,
Vadym Mochalin, Sirma Koutzaki and Boris Polyak
Long term prevention of smooth muscle cell migration and proliferation
inside the lumen of coronary arteries after stent implantation
remains a challenge in medicine. Vascular stents have been
coated with anti-proliferative drugs such as paclitaxel and
rapamycin to improve the stents’ efficacy. Maintaining
adequate drug concentration on coronary stents presents an
obstacle which magnetic nanoparticle (MNP) drug delivery could
potentially overcome. Biodegradable, super-paramagnetic nanoparticles
guided by high gradient magnetic fields have been proposed
as transport vehicles for re-dosing stents with anti-proliferative
drugs. The current study determined the characteristics of
a number of candidate MNP formulations in terms of their size,
surface charge, efficiency of magnetite and drug loadings,
drug release profiles as well as their anti-proliferative
effect on the relevant vascular cells. MNPs containing near
30% (w/w) magnetite and 12% (w/w) paclitaxel were formulated
from polylactide and poly(lactide-co-glycolide) polymers using
an emulsification-solvent evaporation methodology. Drug release
patterns correlated well with cell growth inhibition in cultured
aortic smooth muscle cells and bovine aortic endothelial cells
treated with varying MNP doses. Cell viability assays revealed
MNP dose-dependent cell growth inhibition over an 8-day time
span for paclitaxel-loaded formulations resulting in near
80% and 100% of cell growth arrest in cultured vascular smooth
muscle cells and endothelial cells respectively, while unloaded
with drug formulations showed negligible variation from the
non treated cells. It is concluded, that biodegradable polymeric
superparamagnetic nanoparticles loaded with a relatively high
level of magnetite and drug could serve as efficient carriers
in vascular stent targeting applications and potentially allow
re-dosing the depleted stents, thereby prolonging the lifecycle
of the implant.
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Phosphodiesterase-5 Inhibitor Tadalafil Acts on Endothelial
Progenitor Cells by CXCR4 Signalling
Carlo Foresta, Luca De Toni, Sabina Magagna, Alessandro Galan
and Andrea Garolla
It has been proposed that endothelial progenitor cells (EPC),
originating from the bone marrow contribute to neo-angiogenesis
in vivo by forming endothelial cells. Once released
in the bloodstream, EPC home at the site of vascular damage
where they participate in endothelium regeneration. In this
process CXCR4 plays a key role. Recently we demonstrated that
a prolonged therapy with phosphodiesterase-5 (PDE5) inhibitors
does improve endothelial function and increases circulating
EPC, suggesting a role of PDE5 in EPC physiology. Here we
tested the expression of PDE5 and CXCR4 on cultured, circulating,
and bone marrow resident EPC, and we studied the effect in
vivo and in vitro of PDE5 inhibition after administration
of a PDE5 inhibitor (tadalafil) on EPC, in term of CXCR4 expression.
We documented that in vivo and in vitro
EPC express both PDE5 and CXCR4, and that tadalafil administration
induced a significant increase in EPC number and the relative
CXCR4 expression. This effect is inhibited by selective CXCR4
antagonist. We thus demonstrated that PDE5 inhibition acts
on CXCR4 signalling in EPC and we can suppose an involvement
of cGMP second messenger system in both EPC release from the
bone marrow and EPC-mediated peripheral re-endothelization.
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Topical Dermatological Drug Delivery: Quo Vadis?
Franklin K. Akomeah
Skin disease (dermatological conditions’) affects at
least one-third of the US population and has been cited as
one of the top 15 medical conditions for which prevalence
and healthcare spending increased in the last decade. The
outcome of topical dermatological drug treatment is significantly
influenced by the choice of vehicle or delivery system. Advancements
in the life sciences coupled with a growing market for dermatologicals
have facilitated the emergence of improved topical formulations
and drug delivery systems. The current and emerging approaches
of optimizing the topical delivery of dermatological agents
(small and large molecules) include the use of chemical enhancers,
bio-polymers (e.g. sodium hyaluronate), liposomes, particulate
carriers (microspheres and lipid nanoparticles), topical sprays
and foams, occlusion (via dressings and patches) topical peels,
temperature (heat), iontophoresis and ultrasound. These delivery
approaches (when used solely or in a synergistic manner) are
a significant improvement over conventional systems (creams,
lotions, ointments and pastes) and have the potential to enhance
efficacy and tolerability, improve patient compliance (including
dermatology life quality), and also fulfil other unmet needs
of the topical dermatological market.
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Release of Antithrombotic Drugs from Alginate Gel
Beads
Erik Jämstorp, Aase Bodin, Paul Gatenholm, Anders Jeppsson
and Maria Strømme
The aim of the present work was to evaluate alginate hydrogels
in the form of spherical beads as carrier for antithrombotic
drugs for future use in artificial grafts. The ionotropic
gelation technique was employed to prepare beads from the
L. hyperborea stipe of alginate with two different alginate
concentrations and two different guluronic to manuronic acid
ratios. The beads were loaded, via soaking, with three different
types of low molecular weight model molecules representing
drugs with antithrombotic action and their release characteristics
were subsequently evaluated. The entire release process of
the negatively charged model drugs under study (Salicylic
acid and Hirudin), was found to be governed by diffusion,
while additional electrostatic interactions between drug molecule
and alginate matrix was indicated to influence the release
rate of the analyzed positively charged drug molecule (Dipyridamole).
It was found that the alginate hydrogel matrix imposed a decrease
of the drug diffusion rate on the molecules under study as
compared to the corresponding diffusion rates in water. All
diffusion coefficients decreased slightly with increasing
concentration of alginate and with increasing guluronic to
manuronic acid ratio. The results show on the potential use
of alginate gel beads when developing vehicles for release
of low molecular weight antithrombotic drugs.
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Nanoparticles: A Promising Therapeutic Approach in
Atherosclerosis
Charalambos Antoniades, Costantinos Psarros, Dimitris
Tousoulis, Constantinos Bakogiannis, Cheerag Shirodaria and
Christodoulos Stefanadis
Coronary atherosclerosis is the largest cause of mortality
and morbidity in industrialised countries. Despite recent
advances in medical therapies, the prevention and treatment
of atherosclerosis remain suboptimal. Atherosclerosis is considered
to be a chronic inflammatory disease of the arterial wall,
involving the accumulation of macrophages and excess low density
lipoproteins (LDL), the formation of foam cells which create
the atheromatous plaque, resulting in stenosis, aneurysm and
plaque rupture leading to acute coronary events. Every step
in the atherogenesis process is a potential therapeutic target
for both the prevention and regression of atherosclerosis.
A novel approach is the use of nanoparticles containing drugs,
providing new perspectives in targeted modification of these
pathways. Nanoparticles are ultrafine particles sized between
1-100 nm. By using specific methods, nanoparticles can be
filled with drugs and achieve targeted drug delivery near
the diseased area. In this review article we describe the
basic actions of nanoparticles, and we discuss their potential
applications in atherosclerosis. We also discuss their advantages
and we expose the existing toxicity issues, making it clear
however, that the use of nanoparticles is one of the most
promising therapeutic strategies against atherosclerosis.
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Chloroquine Resistance: Proposed Mechanisms and Countermeasures
Eric Guantai and Kelly Chibale
Malaria has been, and remains, one of the biggest global
health concerns as far as infectious diseases are concerned,
with yearly incidence and mortality figures running into millions.
One of the major drawbacks to the control of this disease
has been the emergence of drug resistant strains of the causative
agent, which limits the successful use of many clinically
available antimalarial drugs. This review discusses chloroquine
resistance; it highlights some of the proposed molecular mechanisms
of chloroquine resistance, but dwells more on efforts at reversing
chloroquine resistance and the concept of chloroquine resistance-reversal
agents.
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Evaluation of Extemporaneously Manufactured Topical
Gels Containing Aceclofenac on Inflammation and Hyperalgesia
in Rats
Kavita Pabreja, Kamal Dua and Satyanaryana
S.V. Padi
The systemic use of non-steroidal anti-inflammatory drugs
(NSAIDs) which act by inhibiting cyclooxygenase (COX) is severely
hampered by gastric and peptic ulcers. The topical delivery
of NSAIDs has the advantages of avoiding gastric and peptic
ulcers and delivering the drug to the inflammation site. Importance
of aceclofenac as a new generational NSAID has inspired the
development of topical dosage forms. This mode of administration
may help to avoid typical side effects of NSAIDs associated
with oral and systemic administration such as gastric irritation,
particularly diarrhoea, nausea, abdominal pain and flatulence.
The aim of this study was to formulate topical gel containing
1% of aceclofenac in carbopol and PEG base and to evaluate
it for analgesic and antiinflammatory activity using carrageenan-induced
thermal hyperalgesia and paw oedema in rats. Carrageenan administration
into the hind paw produced a significant inflammation associated
with hyperalgesia as shown by decreased rat paw withdrawal
latency in response to a thermal stimulus (47±0.5°C)
4 h after carrageenan injection. Topical application of AF1
significantly attenuated the development of hypersensitivity
to thermal stimulus as compared to control (P<0.05)
and other formulation treated groups (P<0.05).
All the AF semisolid formulations, when applied topically
2 h before carrageenan administration, inhibited paw edema
in a time-dependent manner with maximum percent edema inhibition
of 80.33±2.52 achieved with AF1
after 5 h of carrageenan administration However, topical application
of AF2 markedly prevented
the development of edema as compared to other formulation
(AF2 and AF3)
treated groups (P<0.05). Among all the semisolid
formulations, Carbopol gel base was found to be most suitable
de-rmatological base for aceclofenac.
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Effect of Iontophoresis and Permeation Enhancers on
the Permeation of an Acyclovir Gel
Subhash S. Vaghani, Mitesh Gurjar, Sachin Singh, Sunil
Sureja, Shailesh Koradia, N.P. Jivani and M.M. Patel
The purpose of the present study was to explore the combined
effect of chemical enhancers and iontophoresis on the
in vitro permeation of acyclovir gel across porcine skin.
Acyclovir gel was formulated using carbopol 940 and hydroxypropyl
methylcellulose K4M (HPMC K4M). Effect of drug concentration
on the delivery of acyclovir was examined. Increasing drug
concentration of acyclovir enhanced its flux across the skin.
Incorporation of permeation enhancers (menthol, n-methyl-2-pyrrolidone
and polyethylene glycol 400) into the gel resulted in enhanced
acyclovir permeation when combined with iontophoresis. Menthol
showed the highest drug permeation and when combined with
iontophoresis it significantly increased the acyclovir skin
permeation.
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Utilization of Hydrophilic Swellable Polymers as Carriers
for Sustained Drug Delivery from Matrices and three Layer
Tablet Systems
Marilena Vlachou, Hani Naseef and Manuel
Efentakis
The purpose of this research was to develop and evaluate
different sustained release preparations, using swellable
polymers as carriers in the form of matrices and three-layer
tablets. These preparations may offer a number of therapeutic
advantages over immediate release dosage forms in drug delivery.
The materials used for the fabrication of these systems were
hydrophilic swellable polymers namely Metolose, Polyox, Xanthan
gum and an erodible material Gantrez, acting as drug(diclofenac
sodium) carriers. The powder characteristics determined for
these polymers suggest good flowability with the exception
of Gantrez. The addition of 1% of magnesium stearate resulted
in improved flow properties for all polymers including Gantrez.
Tablets were prepared by direct compression whereas three-layer
tablets were prepared by compressing polymer barrier layers
on both sides of the core containing the drug. Our findings
show that both preparations exhibit sustained release characteristics;
also the structure of the device considerably affects the
drug release and the release rate. Furthermore erosion and
swelling greatly influence the overall behavior, function
and performance of the systems. Finally kinetic analysis studies
indicated that the drug release mechanisms were also affected
by these effects.
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