Biopolymers In Drug Delivery: Recent Advances and Challenges

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In the area of drug delivery, various polymers are involved. The earlier polymers were natural in origin. The natural polymers were found to be fraught with many formulation problems such instability, irreproducibility, changes in aesthetics on storage, uncontrollable formulation characteristics, etc. As a result new designer molecules were sought for to solve some of the problems. Some of the natural polymers were largely polysaccharide gums such as acacia, guar, xanthan, agar, tragacanth, etc. These may have their origin plant, seaweed or even fungi. Some bacteria are known to produce polysaccharides that may be useful in medical and pharmaceutical practices. A few polymers may be of animal origin such as gelatin, serum albumin, liposomes, etc. On the other hand, synthetic polymers are either modified from natural polymers or completely synthesized from synthetic monomers. They process properties that seem to relatively address the problems of instability, irreproducibility, changes in aesthetics on storage, uncontrollable formulation characteristics. The environment of use in the body is often considered in the preparation of these polymers. Good examples are the derivates of the acrylic resins, vinyl polymers, cellulose polymers, etc. Various aspects of these two classes of polymers are presented in this chapter.

A volume of attention is currently being drawn to the potentials inherent in African tropical plants as sources of bioactive substances and drug carriers as well as adjuncts in the formulation of drug delivery systems. One group of such carriers or adjuvants consists of polymeric plant metabolites, which can hydrate into gels or mucilages. These are generally known as plant gums. Although gums obtained from African tropical plants have been known for a very long time, their extraction, purification and utilization in pharmaceutical formulations are still at rudimentary stages. There appears to be greater industrial preference for synthetic or semi-synthetic hydrogels as vehicles, carriers and excipients in pharmaceutical, cosmetic or food products. But because of the naturalness of biopolymers of plant origin, with associated inertness and safety, more interest has to be shown, particularly by the pharmaceutical industry, towards the employment of plant gums as drug carriers, or adjuncts, in drug dosage forms. This article seeks to draw attention to some African tropical plant gums, obtained from different plant species, which have been shown, via laboratory studies, to exhibit potential applicability in the development of drug delivery systems.

Mucins are the major macromolecular constituents of the mucous secretions that coat the oral cavity and the respiratory, gastrointestinal and urinogenital tracts of animal. They are responsible for the viscoelastic properties of the secretions, providing protection for the exposed delicate epithelial surfaces from microbial and physical injuries. Secretory mucins are typically of very high molecular mass (over 1 mDa) and have hundreds of O-linked saccharides constituting between 50% and 80% of the molecule by weight. The saccharides are based, at present, on seven core structures and can vary in length from disaccharides to oligosaccharides of approximated 20 monosacharides and exhibit astonishing diversity. The biological relevance of this diversity is not fully understood, but one possibility is that they act as ‘decoy’ receptors for the prevention from binding of pathogens to epithelial cell. It has been shown for a long time that the saccharides are linked to serine and threonine residues of the protein scaffold. However, owing to the technical problems associated with deglycosylation of mucins, the biochemical characterization of the protein backbone of the large discrete mucins has been fraught with difficulties. Mucins play a key role in the host intestine. From acting as a protective, physical barrier, they are responsible for producing certain protective enzymes that are responsible for the host intestinal defensive mechanism. The defensins and magainins that protect the host in the intestine are largely responsible for the prevention of many microbial diseases. The integrity of the intestinal mucin may also help as a physical barrier to the entrance of bacteria to the underling tissue. Thus organisms that produce enzymes capable of hydrolyzing mucins can easily establish infections. Thus, the microorganisms that produce sialidases are capable of hydrolyzing cervical mucin and such organisms have been implicated in the pathogenesis of sexually transmitted infections in the female genital tract. Hence, the detection of these enzymes may be indicative of the presence of invading organisms and may be used as a diagnostic tool. Mucins may play a key role in the pharmaceutical industry as a drug delivery agent if properly harnessed. Mucins are ubiquitous in many human tissues. Thus we can talk of intestinal, ocular, ovarian and salivary mucins, etc. They are also negatively charged. This makes mucin a good candidate for drug delivery as they can be conjugated to positively charged drug molecules and targeted to the respective tissues. Its biomaterial properties can readily be modified by the use of other cationic polymers such as chitosan. Apart from the modification of the biomaterials properties, cationic polymers help to stabilize mucin as it can readily degrade to its motifs. Their viscosity and solubility properties can readily be modified using micro-molar concentrations of ethylene diamine tetra-acetic acid (EDTA) which chelates the calcium content of muicn. It is highly biocompatible, non-toxic and easily biodegradable. Mucins are often used for modelling of mucoadhesive and bioadhesive systems. Thus the interpenetration of various polymers at the mucin-polymer interface at a temperature higher than the glass transition temperature is often used to explain the mechanism of mucoadhesion. The molecular bridges which result between mucin-polymer interpenetration accounts for the adhesive strength. Apart from these bridges, the electronic properties of mucin help in mucoadhesion. Mucin, therefore, has high potential as a pharmaceutical excipient if adequately harnessed

Starches are carbohydrate polymeric substances mostly structurally composed of straight-chain amylose units with branched chain amylopectin. They are synthesized within the plant by the chemical interlinking of hundreds and thousands of individual glucose units to form long-chain molecules, and treatment with acid or enzymes can break the starch down to its constituent glucose molecules. They form the major food reserve materials in plants especially in the seeds and tubers. Starches have found wide uses in various segments of life, especially agricultural, pharmaceutical, food and chemical sectors and are reportedly the most important hydrocolloids both on a weight and money basis. Over the years, it has been possible to structurally modify starches to achieve an improvement in their utility in the various segments of their application. Such modifications impart new properties, improve some of the inherent properties, or repress and modify some of their other properties. The modification involves a change in the functional properties of the starch, which may manifest as changes in granule size, colour, flavour, odour, moisture content, flowability and dispersibility in different media, among others. Several techniques have been employed in modification of starches including heating, hydrolysis (acid or alkali), oxidation with oxidizing chemicals, addition of chemicals that will result in the introduction of new chemical groups and/or changes in the size, shape and structure of the starch molecules, extrusion cooking and cross-linking. In the pharmaceutical sector, modified starches have found great use in the development of conventional and novel drug delivery systems. They have specifically been utilized as efficient binders in tablet and granule formulations, disintegrants in tablet formulations, diluents in tablet, granule, capsule and powder formulations; and matrices for specialized (sustained, targeted, regulated) drug delivery systems.

Effective delivery of therapeutic genes to target cells is an essential goal of all innovative gene therapy endeavours and recombinant vaccine technology. Current use of viral vectors in achieving this goal has been associated with minimal success and plethora of unwanted adverse events. As a result, there is an ongoing search for suitable vector platforms for the delivery of therapeutic genes to target cells. Such agent should be easily manipulated to accommodate small and large gene inserts and safely deliver Transgenes. This will ensure effective expression of the gene in target cells. The resulting optimal expression of this gene may correct defective or deficient gene in individuals receiving gene therapy. This chapter examines the applications of biopolymers as non-viral gene delivery vectors either alone or as copolymers.

Polymers fall into three broad categories: natural, semi-synthetic and synthetic. Polymers are widely used in pharmaceutical systems as drug carriers, adjuvants, suspending and emulsifying agents. The word "polymer" which means "many parts", is derived from the Greek words poly, meaning "many," and meros, meaning "parts". Polymers are widely found in nature and occur in many forms. The human body contains many natural polymers such as proteins and nucleic acids, while cellulose is the main structural component of plants. Cellulose, starch, lignin, chitin, and various polysaccharides are of natural origin. These materials and their derivatives offer a wide range of properties and applications in drug delivery. Natural polymers are usually biocompatible and biodegradable. In this chapter, sources and applications of natural biopolymers in particulate drug delivery systems such as microparticles and nanoparticles, which are currently widely investigated as drug delivery systems, were discussed.

Cross-links are bonds that link one polymer chain to another. These bonds can either be covalent or ionic in nature. In polymer science, the use of cross-links to promote a difference in a polymer’s physical properties is referred to as cross-linking. When polymer chains are linked together by cross-links, they lose some of their ability to move as individual polymer chains. For example, a liquid polymer, which possesses freely flowing chains can be turned into a “solid” or “gel” by cross-linking the chains together. Cross-linking inhibits close packing of the polymer chains, preventing the formation of crystalline regions. The restricted molecular mobility of a cross-linked structure limits the extension of the polymer material under loading. This means that when a polymer is stretched, the cross-links prevent the individual chains from sliding past each other. In the process, the chains may straighten out, but once the stress is removed they return to their original position and the object returns to its original shape. It is a well known fact that polymers with a high enough degree of crosslinking have “memory”. With this “memory”, such cross-linked polymers can be exploited for a number of useful purposes including modifications for improved drug delivery and release. Several reports have indicated that the cross-linking density, molecular weight, electrical charge of polymers and other factors might have a profound effect on the release rate of drugs from polymer-based multiparticulate drug delivery systems. Among these factors, the modification of the cross-linking density is expected to be the most useful for optimizing the release rate of drugs, including peptides, from such systems. Alteration of the cross-linking conditions almost always results in changes in the cross-linking density of biopolymers. Both the prolongation of the cross-linking reaction time and an increase in concentrations of crosslinking agent have been reported to increase the cross-linking density of gelatin and other biopolymers. These reports suggest that polymers with desirable cross-linking density could be obtained by optimizing the conditions of the cross-linking reaction. The cross-linking density of polymers such as alginate and collagen could also be altered by modifying the cross-linking reaction time and the concentration of the cross-linking agent. In fact, previous reports have demonstrated that as the cross-linking density became higher, the amount of insulin released from gelatin microspheres in the initial phase decreased. A burst release of insulin, however, was also reported for gelatin microspheres with a low cross-linking density because of the structural weakness of such microspheres. This chapter will, therefore, focus on how drug delivery and release can be improved and/or controlled by altering the cross-linking density of biopolymers using well known polymers as illustrations. Optimization of this technique would be useful when designing biopolymer-based multiparticulate systems for drug delivery.

Drug delivery and pharmacokinetics have remained important components of therapeutic and biomedical practice for many decades. In recent time, the world has witnessed rapid progress in developments of different drug delivery protocols, especially as it regards the use of degradable biopolymers. This became a viable research and economic venture with parallel progress in inter-related fields of biomaterial science, biotechnology, nanotechnology and pharmacology. Recent advances in material science, biomaterial development and tissue engineering are changing the face of medicine in the present age. Biopolymers and drug delivery systems offer the “ideal” conceptual framework for improving the efficacy of existing drug formulations and developing new treatments. Interestingly, there are extensive researches so far carried out in the area of biodegradable materials for controlled release of drug which circumvents the need for removal of non-degradable drug-depleted devices. Many biodegradable polymers have been evaluated for their suitability as matrix for drugs, including polyesters, polycarbonates, natural and synthetic polyamides, phosphate esters, polyphosphazenes and polyanhydrides. Current and novel drug delivery approaches involve the application of these polymers in a variety of devices, including biodegradable polymer shape-memory polymers, targeted nanoparticle conjugates and miniaturized drug delivery devices. These approaches have greatly improved the delivery of drugs to target sites that would have been ordinarily impossible by conventional therapeutic routes. In this chapter, we will discus some key recent and relevant advances in the use of biopolymers for drug delivery. Thereafter, the challenges still ahead will be presented. In all, biopolymers promise rewarding prospects for the world in this 21st century and beyond.

This chapter discusses synthetic biopolymers and their application in drug delivery. Numerous delivery techniques, taking advantage of the functional properties of synthetic polymers, have been successfully developed for various routes of administration. A polymer is synthesized by chemically combining many small molecules to form one giant molecule. Synthetic polymers can be classified as addition polymers or condensation polymers, formed from monomer units. Currently, synthetic materials with biomimetic properties are attracting growing attention as possible new dosage forms or drug delivery platforms and the potential applications of these increasingly sophisticated polymers in drug delivery will be discussed. This chapter treats synthetic biopolymers according to the following format: Introduction to biopolymers; General uses of biopolymers; Classes of synthetic and biosynthetic biopolymers; Some synthetic schemes of biopolymers; Special uses and applications of synthetic biopolymers in drug delivery; Advantages of synthetic biopolymers in drug delivery; Limitations of synthetic biopolymers; The future of synthetic biopolymers.

Suitability of the nasal route for both local and systemic delivery of drug substances stems from several advantages including high vascularity, large surface area, avoidance of firstpass metabolism, ease of drug administration, rapid attainment of therapeutic blood drug levels and possibly high systemic bioavailability. In spite of these advantages, there are some challenges facing this non-invasive drug delivery approach. Rapid removal of administered drugs by respiratory mucociliary clearance system often results in low absorption, especially for large molecular weight compounds. This problem may be addressed using novel delivery systems such as mucoadhesive formulations. This chapter will focus on novel formulation strategies with synthetic biopolymers for systemic drug delivery via the nasal route.

Synthetic biopolymers (especially the biodegradable polymers) have been extensively researched for their applications in targeted and controlled release (CR) of different therapeutic agents. These synthetic polymers, including (but not limited to) polylactide-polyglycolide copolymers, polyacrylates and polycaprolactones, are being increasingly used in the formulation of novel microparticulate and nanoparticulate delivery systems. The applicability of microparticles and nanoparticles based on these synthetic biopolymers in protein, drug, vaccine delivery and gene therapy is rapidly expanding. In this chapter, we have focused on this novel synthetic biopolymer technology as it relates to the delivery of genes and therapeutic proteins: the syntheses and characterization of the particles, encapsulation or loading of therapeutic agents, protein/gene stability, release and expression. The toxic and safety issues in connection with use of these synthetic biopolymers and the potential usefulness of this delivery system are also discussed.

Biopolymers have a myriad of applications which may be considered as novel not only in agriculture and agribusiness, consumer science, sports, transparent and optical materials and in biological and medical materials but also in controlled drug delivery and targeting. This chapter will highlight the major applications of biopolymers as enunciated in the preceding sentence with special emphasis on the use of engineered polymers and polymeric systems in controlled drug delivery and targeting. Successful pharmacotherapy intervention requires strict control over the spatial and temporal characteristics of drug delivery. Engineered polymers are the materials used today to construct carriers with controlled drug delivery properties, that is, carriers which could perform one or more of the following: (a) increase drug availability to the target cells, (b) increase selectivity towards the target cells, (c) release their drug load only at the site of drug action (or nearby) in response to internal or external stimuli (e.g. pH or temperature changes) and (d) release drug only when it is required in response to biological signals (e.g. an increase in glucose levels in blood). The development of such polymers has caused advances in polymer chemistry, which, in turn, has resulted in smart polymers that can respond to changes in environmental conditions. The responses vary widely from swelling/deswelling to degradation. Drug-polymer conjugates and drug-containing nano/micro-particles have been used for drug targeting. Engineered polymers and polymeric systems have been used in new areas, such as molecular imaging as well as in more recent applications in nanotechnology.

Biopolymers are important class of materials for pharmaceutical and biotechnological applications. Studies have been carried out on different biopolymer blends and types. The area of biopolymer interactions has been the focus of intensive fundamental and applied research in recent time. Such biopolymer combinations may possess unique properties that are different from those of individual components. There is a great potential in utilizing biopolymer blends as pharmaceutical adjuvants and in controlled release drug delivery systems. Appropriate selection of biopolymer or biopolymer blend is necessary in order to develop a successful drug delivery vehicle. In drug delivery, the biopolymer blends used should be designed in such a way that their functionality remains constant throughout an application. For a successful industrial development of a viable dosage form using biopolymer blends, the biopolymers selected must be pharmaceutically approved and should also demonstrate acceptable mechanical and biocompatible properties. Biopolymer blends used in drug delivery are characterized to establish their suitability for the intended dosage form. In this chapter, biopolymer blends used in drug delivery are discussed with particular emphasis on their formation, properties, characterization, applications and their limitations and future prospects.