Natural Polymers for Drug Delivery

Harsha Kharkwal, Srinivas Janaswamy, Harsha Kharkwal, Srinivas Janaswamy

• Publisher: CAB International
• Year: 2016
• ISBN:
  9781786390745
• Topic: Medicina
• Subtopic: Bioquímica en medicina

Natural polymers have been utilized extensively in food, pharmaceuticals, cosmetics, textiles, oil drilling and paint industries. Their non-toxic and inexpensive attributes readily enhance their commercial acceptability and make them potent agents in lieu of synthetic polymers.This book explores the opportunistic utility of natural polymers in developing effective drug delivery systems and provides a comprehensive and up-to-date analysis of their source, chemical structure and mechanism of action. Covering novel polymers for drug delivery - in particular extracts from plants, microorganisms and proteins, as well as water soluble and water insoluble biodegradable polymers - it presents an encyclopaedic overview of natural polymers': - quintessential roles in binding drugs towards enhancing bioavailability- modification and derivatization for targeted delivery- role as active drugsNatural Polymers for Drug Delivery is an invaluable resource for researchers, students and industrial scientists in the fields of biochemistry, chemistry, pharmacology and food science.

1 Natural Polymers for Drug Delivery: An Introduction

Harsha Kharkwal^1,* Bhanu Malhotra² and Srinivas Janaswamy³

¹Amity Center for Carbohydrate Research and Amity Institute of Phytomedicine and Phytochemistry, Amity University, Noida, India; ²Amity Institute of Biotechnology and Amity Center for Carbohydrate Research, Amity University, Noida, India; ³Department of Dairy and Food Science, South Dakota State University, South Dakota, USA

^* Corresponding author. E-mail: [email protected]

Abstract

Natural polymers are macromolecules composed of repeating structural units joined by covalent bonds. Carbohydrates, proteins and muscle fibres are known examples and have potential as drug delivery systems. A typical delivery system aims at slow and tissue-specific release, and as natural polymers exhibit biodegradability and biocompatibility they are well suited for this purpose. Natural polymers are also utilized as excipients and over the years, new advances in the treatment of diseases using the approach of site specific drug delivery by the utilization of polymers have emerged with several promises. This chapter highlights some available examples with an emphasis on their potent applications and properties in the drug domain.

Introduction

A polymer is a macromolecule with repeating monomeric structural units joined covalently. Carbohydrates, proteins and muscle fibres are common types of polymers. Carbohydrates are polyhydroxy aldehydes or ketones, and could be further classified as monosaccharides, disaccharides and polysaccharides. A polysaccharide consists of more than 20 repeating monomeric units. Polysaccharides can be homopolysaccharides if they contain only one repeating monomeric unit (e.g. cellulose, glycogen, starch and chitin), or heteropolysaccharides if two or more different kinds of monomers are present (e.g. peptidoglycan bacterial cell walls and glycosaminoglycans) (Pérez and Mulloy, 2005). These natural systems can be modified chemically to create biocompatible and biodegradable non-toxic entities, and have readily gained popularity in the pharmaceutical industry as drug delivery agents ( Harborne, 1987). Plant-based polymers have also been investigated for this purpose. In addition, various liquid ophthalmic suspensions, buccal films, film-coating agents and microspheres have been proven to be effective (Pandey and Khuller, 2004; Chamarthy and Pinal, 2008; Alonso-Sande et al., 2009).

The history of using silicone rubber as a carrier (Folkman and Long, 1964) set the stage for the design and development of prolonged drug delivery systems, and since then the use of polymers in drug therapy has advanced significantly. Several scientific journals highlight the use of polymers as drug vehicles, and Table 1.1 gives an historical perspective with citations of published articles in Advanced Drug Delivery Reviews, according to the Web of Science core collection in 2014.

Table 1.1. Top polymer related reviews cited in ‘Advanced Drug Delivery Reviews’ according to Web of Science core collection in 2014. (Adapted, with permission, from Merkle, 2015.)

The need for natural polymers

Research has focused on the beneficial properties of natural polymers, especially towards delivering toxic therapeutic agents to the target tissue. The use of natural polymers and their derivatives not only enhances the drug availability at the target tissues, but is also regarded as a safe means of delivery. Some of the special characteristics of natural polymers that are attractive are their:

• Biodegradability – they pose no harmful environmental effect and are 100% biodegradable.

• Lack of toxicity – they are non-toxic.

• Economy – they are inexpensive and large quantities can easily be obtained.

• Safety – their natural availability bestows the required safety without any harmful side effects.

• Availability – they are widely distributed globally; for example, cellulose can easily be extracted in large quantities (Prajapati et al., 2013).

Some of the disadvantages include the chances of microbial contamination when exposed to the external environment, uncontrolled hydration rate because of differences in availability and the presence of different species.

Classification of Natural Polymers

Natural polymers, mainly polysaccharides, are obtained from various sources including plants, microbes, algae and fungae. Some are neutral and others, such as the carboxylate or sulfate groups, possess a negative charge. Chitosan is the only cationic polysaccharide currently known (Fig. 1.1).

• Plant origin – starch, hemicellulose, cellulose, agar, glucomannan, pectin, guar gum, locust bean gum, gum acacia, gum tragacanth and psyllium

• Microbial origin – curdlan, gellan, xanthan

• Algal origin – alginate, carrageenan

• Fungal origin – chitin, pullulan, scleroglucan

Fig. 1.1. Classification of polysaccharides used in drug delivery.

Drug Delivery Applications of Polysaccharides

Polysaccharides are used as coating agents, polymer matrices, tablets formulations, and emulsifying and gelling agents (Prajapati et al., 2013).

Tablet adjuvant formulations

Polysaccharides have been used in tablet formulation due to their inherent adhesive nature. They adsorb large amount of water and swell, so acting as disintegrants. They also provide cohesiveness to the powder formulations and can easily be incorporated into tablets or granules (e.g. guar gum and acacia).

Mucoadhesive agents

Their main purpose is to control release of the drugs over a stipulated time. Furthermore, they can be retained in the intestinal lining and stomach for longer durations, enhancing drug absorption (e.g. karaya gum and sodium alginate).

Emulsifying and suspending agents

Natural polymers provide stability to emulsions because of their interfacial absorption. They can also form films with high tensile strength and resist coalescence among the droplets (e.g. xanthan gum and acacia gum).

Gelling agents

Mucilage and gums form gels either alone or in combinations with other gums. The gelation is due to inter-and intra-molecular associations among the chains leading to three-dimensional networks that can, in turn, trap large amounts of water. These formulations can be prepared through physical methods, for example changing pH and temperature, as well as by chemical treatments through adding suitable reagents. Examples include carrageenan and locust bean gum.

Coating agents

Certain natural polymers have the intrinsic ability to act as coating agents that protect the drugs from degradation and allow release in a controlled manner (e.g. pectin and sodium alginate).

Sustaining agents in dosage form

Matrix tablets are the most prominent oral drug delivery systems because of their sustained release and easy formulation properties (e.g. locust bean gum and karaya gum).

The main purpose of developing drug delivery systems casting polymers is to abolish any toxic product accumulation inside the body. This is quite feasible as natural polysaccharides do not generate any unusual products inside the body. Instead, they are eliminated easily as carbohydrate units during the regular metabolic processes, and so the polysaccharide disappears after serving its purpose. The biodegradation proceeds with bond breakage within the monomers leading to erosion of the bulk polymer (Peppas, 1984). Various routes cause polymer degradation:

• hydrolysis;

• photolysis;

• its solubilising nature;

• brittleness;

• biodegradation;

• thermo-degradation; and

• structural weakening.

Polymer Drug Release Mechanism

The therapeutic agents attached to the polymers can be released at a controlled rate from the polymeric matrices via different mechanisms. The delivery of a drug over a specified time period to the tissues exploits various properties of polymers. One prominent example is that of stimuli-sensitive polymers releasing the drug only when there is a change in pH or temperature (Kaur et al., 2014).

Degradation

Certain biodegradable polymers degrade inside the body under normal physiological and biological processes. They can also be designed to break under hydrolysing conditions, which results in smaller and manageable chain lengths without any side effects.

Diffusion

A reservoir device is often used, where the drug is located in the core of the tablet, capsule or polymeric network with a shell surrounding it. The shell might be composed of some type of polymer that will dictate the rate of diffusion of the drug from the core. With this mechanism, water will diffuse into the core and dissolve the drug inside, which will then diffuse out. Swelling or degradation of the shell can occur, depending on the polymer. Two different types of diffusion systems exist:

1. Only dissolved drug within the core. The drug load decreases over time as it diffuses out of the core.

2. Initial drug concentration within the core is higher than the aqueous solubility concentration. As the dissolved drug diffuses out more, an amount of drug is dissolved within the core, and the drug load will be constant for a longer period of time.

Swelling

Swelling is another type of controlling phenomenon involved in drug delivery. The matrix former has the capacity to swell and control the drug release rate. When polymer swelling leads to an increase in the length of diffusion pathways, the system volume increases, lowering the drug concentration gradient. This results in a slower release of the drug into the bulk system. In contrast, swelling of the polymer can enhance the molecular mobility, leading to faster release.

Overall, immense progress has been made in diffusion-controlled systems and solvent-activated formulations of drug release. Also, through the use of hydrogels and various other polymeric carrier systems, it is now possible to establish a very safe passage for the therapeutic drug to the target regions, and more importantly to inhospitable physiological regions. Polymeric substances having a controlled molecular architecture can be specifically engineered to provide response to the external stimulus. It has been shown that the therapeutic agents conjugated to the polymer show relatively improved drug release kinetics by preventing carrier accumulation. Polymer drug conjugates also help to improve the circulatory half-life for the cytoplasmic delivery of therapeutics.

Natural Polymers in Drug Delivery

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Table of contents

• Cover
• Half Title
• Dedication
• Title
• Copyright
• Contents
• List of Contributors
• 1 Natural Polymers for Drug Delivery: An Introduction
• 2 Cellulose-based Polymeric Systems in Drug Delivery
• 3 Hydrocolloid-based Hydrogels in Drug Delivery
• 4 Water-soluble Biodegradable Polymers for Drug Delivery
• 5 Polysaccharide-based Drug Carriers
• 6 Polymer-based Nanoparticles for Drug Delivery Systems and Cancer Therapeutics
• 7 Polymer Nanocomposite-based Biosensors for Drug Delivery Applications
• 8 Polymer–drug Conjugates: Targeted Drug Delivery
• 9 Protein–Drug Conjugates: A New Class of Biotherapeutics
• 10 Microencapsulation for Controlled Gastrointestinal Delivery of Probiotics and Prebiotics
• 11 Chitosan in Drug Delivery and Targeting for Cancer Treatment
• 12 Polymers as Biodegradable Matrices in Transdermal Drug Delivery Systems
• 13 Ocular Drug Delivery Systems
• 14 Polymers Targeting Habitual Diseases
• 15 Bioengineered Wound and Burn Healing Substitutes: Novel Design for Biomedical Applications and General Aspects
• Index
• Back Cover