Biopolymers Efficient Drug Delivery

27Packaging India October - November, 2010

AbstractThe earth has finite resources in terms of fossil fuel and a finite capacity for disposal of waste. Biopolymers may offer a solution to both these issues in the long-term. In recent years, biopolymers has attracted much attention in the application in packaging and controlled drug release.

This review sets out to examine the current trends in biopolymer science. The different types of biopolymers that have been studied here include starch, cellulose, chitin, protein, casein, PLA, PHA etc. This review also covers the thrust application areas of biopolymers in packaging and controlled drug release and explains the different factors related to biopolymers which affects the drug delivery systems.

IntroductionBiopolymers have been around for billions of years longer than synthetic polymers like

plastics. They are macromolecules of biological origin.

The input materials for the production of these polymers may be either renewable (based on agricultural plant or animal products) or synthetic. All linear biopolymers have a defined beginning and end. Biopolymer synthesis is an anabolic process (requires energy input). All biopolymers are synthesised in one direction only. Some of

Aastha Santanu DuttaSr. Lecturer in MIT,Aurangabad

Bhupendra SinghMaze Cards India Pvt. Ltd.

Today, biobased polymers are gaining importance because conventional resources as well as polymers being used are proving hazardous to our environment. In the days to come more and more stress will be exerted on such ecofriendly sources so as to save our environment.

28 Packaging India October - November, 2010

the monomer is lost in polymerisation, leaving a ‘residue’ incorporated in the growing chain.

Biopolymers largely affect the drug delivery systems. The polymer or matrix defines the release rate and the target for delivery, which is a very important aspect of drug delivery. Hydrophobic drugs are very difficult to deliver in human body as the system is hydrophilic. This problem can be solved by using hyperbranched polymer or dendrimers which are capable of encapsulating hydrophobic drug and simultaneously soluble with hydrophilic system.

Biopolymers are also important for their application in tissue specific delivery systems.

Classification of BiopolymersBiobased polymers may be divided into three main categories based on their origin and production:

Class-I:Polymers directly extracted/ removed from biomass. Examples are polysaccharides such as starch, cellulose and proteins like casein and gluten.l Starch: It is the storage polysaccharide of

cereals, legumes and tubers, is a renewable and widely available raw material suitable for a variety of industrial uses. Corn is the primary source of starch, although considerable amount of starch are produced from potato, wheat and rice in Europe, Asia and the United States. Starch is economically competitive with petroleum and has been used in several methods for preparing compostable plastics.

l Cellulose: It is the most abundantly occurring natural polymer on earth and is an almost linear polymer of anhydroglucose. On account of its regular structure and array of hydroxyl groups, it tends to form strong hydrogen bonded crystalline microfibrils and fibres and is most familiar in the form of paper or cardboard in the packaging context. Cellulose is a cheap raw material, but difficult to use because of its hydrophilic nature, insolubility and crystalline structure.

l Chitin: It is a naturally occurring macromolecule present in the exoskeleton of invertebrates and represents the second most abundant polysaccharide resource after cellulose. In general, chitosan has numerous uses, as flocculants, clarifier, thickener, gas selective membrane, plant disease resistance

Due to their biodegradability and biocompatibility these biopolyesters may easily find industrial applications.

promoter, wound healing promoting agent and antimicrobial agent.

l Proteins: It can be divided into proteins from plant origin (e.g. gluten, soy, pea and potato) and proteins from animal origin (e.g. casein, whey, collagen and keratin). Protein is considered to be a random copolymer of amino acids and the side chains are highly suitable for chemical modification which is helpful to the material engineer when tailoring the required properties of the packaging material. Due to their excellent gas barrier properties, materials based on proteins are highly suitable for packaging purposes.

l Casein: It is a milk-derived protein. It is easily processable due to its random coil structure. Upon processing with suitable plasticisers at temperatures of 80–100°C, materials can be made with mechanical performance varying from stiff and brittle to flexible and tough performance. Casein melts are highly stretchable making them suitable for film blowing.

l Gluten: It is the main storage protein in wheat and corn. Wheat is an important cereal crop because of its ability to form viscoelastic dough. Mechanical treatment of gluten leads to disulphide bridge formation formed by the amino acid cysteine which is relatively abundant in gluten. Processing temperatures depend on the plasticiser contents, in the range of 70–100°C.

l Soy Proteins: These are commercially available as soy flour, soy concentrate and soy isolate, all differing in protein content. Soy protein consists of two major protein fractions referred to as the 7S (conglycinin, 35%) and 11S (glycinin, 52%) fraction. Both, 7S and 11S contain cysteine residues leading to disulphide bridge formation and processing is, therefore, similar to gluten with similar mechanical properties. The most successful applications of soy proteins were the use in adhesives, inks and paper coatings.

l Keratin: It is by far the cheapest protein. It can be extracted from waste streams such as hair, nails and feathers. Due to its structure and a high content of cysteine groups, keratin is also the most difficult protein to process. After processing, a fully biodegradable, water-insoluble plastic is obtained.


l Collagen: It is a fibrous structural protein in animal tissue, particularly in skin, bones and tissues with a common repeating unit, glycine, praline and hydroproline. It is a flexible polymer but due to its complex helical and fibrous structure, it is very difficult to process4,11.

Class-II:Polymers produced by classical chemical synthesis using renewable biobased monomers. A good example is polylactic acid, a biopolyester polymerised from lactic acid monomers. The monomers themselves may be produced via fermentation of carbohydrate feedstock.

l Polylactic Acid: Lactic acid, the monomer of polylactic acid (PLA), may easily be produced by fermentation of carbohydrate feedstock. The carbohydrate feedstock may be agricultural products such as maize, wheat or alternatively may consist of waste products from agriculture or the food industry, such as molasses, whey, green juice etc. Recent results point out that a cost-effective production of PLA can be based on the use of green juice, a waste product from the production of animal feeds. PLA is polyester with a high potential

The greatest advantage of these degradable polymers is that they are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways.

for packaging applications. The properties of the PLA material are highly related to the ratio between the two mesoforms (L or D) of the lactic acid monomer. Using 100% L-PLA results in a material with a very high melting point and high crystallinity. If a mixture of D- and L- PLA is used instead of just the L-isomer, an amorphous polymer is obtained with a Tg of 60°C, which will be too low for some packaging purposes.

Class-IIIPolymers produced by microorganisms or genetically modified bacteria. To date, this group of biobased polymers consists mainly of the polyhydroxyalkonoates, but developments with bacterial cellulose are in progress. The three categories are presented in schematic form in Table 1.

l P o l y - h y d r o x y b u t y r a t e - c o -hydroxyvalerate (PHBV): It is a copolymer of 3-hydroxybutanoic acid and 3-hydroxypentanoic acid, in which the monomer units are connected by ester linkages. The properties of PHBV vary according to the ratio of both the acids, 3-hydroxybutanoic acid

Biodegradable Polymers

Biomass Product fromagro resources

From micro-organism(obtained by extraction)

Polycaprolactone(PCL)

Polyetheramide(PEA)

Aliphatic Co-Polyester(e.g. PBSA)

Aromatic Co-polyester(e.g. PBAT)

From BiotechnologyFrom petrochemicals

Products (ConventionalSynthesis from synthetic

monomers)

Polysacccaride

Starch, wheat, Potatoes

Animal, Casein, whey

Plant: zein, soya gluten

Agro-Cellulosic Product: wood,

straws

Others Pectins, chitoson and gum

Proteins and Lipids Polyhydroxy Alkanoates(PHA)

Polyhydroxy Butyrate(PHB)

Polylactides

Polylactic Acid

Table: 1 Classification of Biopolymers


provides stiffness and 3-hydroxypentanoic acid imparts flexibility to the copolymer. It is used in speciality packaging, orthopaedic devices and even in controlled drug release. When a drug is put into a capsule of PHBV, it is released only after the polymer is degraded. PHBV also undergoes bacterial degradation in the environment.

l Poly (hydroxyalkanoates) (PHAs): Out of these poly (hydroxybutyrate) (PHB) is the most common, are accumulated by a large number of bacteria as energy and carbon reserves. Due to their biodegradability and biocompatibility, these biopolyesters may easily find industrial applications. The monomer composition of PHAs depends on the nature of the carbon source and microorganisms used. PHB is a typical highly crystalline thermoplastic whereas the medium chain lengths PHAs are elastomers with low melting points and a relatively lower degree of crystallinity. A very interesting property of PHAs with respect to food packaging applications is their low water vapour permeability which is close to that of LDPE. Recent application developments based on medium chain length PHAs range from high solid alkyd-like paints to pressure sensitive adhesives, biodegradable cheese coatings and biodegradable rubbers.

l Bacterial Cellulose: It is rather unexploited, but it represents a polymeric material with major potential. Bacterial strains of Acetobacter Xylinum and A. Pasteurianus are able to produce an almost pure form of cellulose (homo-beta-1, 4-glucan). Its chemical and physical structure is identical to the cellulose formed in plants. Bacterial cellulose is processed under ambient conditions and the degree of polymerisation is 15000, 15 times longer than cellulose from wood pulp. It is highly crystalline. It is 70% in the form of cellulose I and the rest is amorphous. This composition results in outstanding material properties, a modulus as high as 15–30 GPa was determined across the plane of the film. Production costs of bacterial cellulose are high due to the low efficiency of the bacterial process; approximately 10% of the glucose used in the process is incorporated in the cellulose. The high price of bacterial cellulose hampers its

applicability in low-added-value bulk products. The material has been used as an artificial skin, as a food grade non-digestible fibre, as an acoustic membrane and as a separation membrane.

Polymers Versus BiopolymersA major, but defining difference between polymers and biopolymers can be found in their structures. Polymers, including biopolymers, are made of repetitive units called monomers. Biopolymers often have a well defined structure, though this is not a defining characteristic (example: ligno-cellulose). The exact chemical composition and the sequence in which these units are arranged are called the primary structure in the case of proteins. Many biopolymers spontaneously fold into characteristic compact shapes as well as secondary structure and tertiary structure, which determine their biological functions and depend in a complicated way on their primary structures. Structural biology is the study of the structural properties of biopolymers. In contrast, most synthetic polymers have much simpler and more random (or stochastic) structures. This fact leads to a molecular mass distribution that is missing in biopolymers. In fact, as their synthesis is controlled by a template directed process in most vivo systems, all biopolymers of a type (say one specific protein) are all alike: they all contain the similar sequences and number of monomers and thus all have the same mass. This phenomenon is called monodispersity in contrast to the polydispersity encountered in synthetic polymers. As a result, biopolymers have a polydispersity index of 1.

Advantages of BiopolymersBesides being available on a sustainable basis, biopolymers have several economic and environmental advantages. Biopolymers could also prove an asset to waste processing. For example, replacing the polyethylene used in coated papers by a biopolymer could help eliminate plastic scraps occurring in compost. Consumers have a lively interest in biopolymers too. Conventional plastics are often seen as environmentally unfriendly. Sustainable plastics could, therefore, provide an image advantage.

The major advantage of biodegradable packaging is that it can be composted, but the biodegradability of raw materials does not necessarily mean that the

The major advantage of biodegradable packaging is that it can be composted but the biodegradability of raw materials does not necessarily mean that the product or package made from them (e.g. coated paper)is itself compostable.


product or package made from them (e.g. coated paper) is itself compostable.

Disadvantages of Biopolymers A disadvantage of chemical modification of biopolymer is that the biodegradability of the polymer may be adversely affected; therefore it is often necessary to seek a compromise between the desired material properties and biodegradability2.

Applications of BiopolymersBiopolymers find applications in nearly every field of life. They are being used in agriculture, medical, automotives, packaging etc. A brief outline of the various biopolymers and their fields of application are listed below:Drug Delivery SystemsControlled drug delivery occurs when a polymer, whether natural or synthetic, is judiciously combined with a drug or other active agent in such a way that the active agent is released from the material in a predesigned manner. The release of the active agent may be constant over a long period, it may be cyclic over a long period or it may be triggered by the environment or other external events.

In any case, the purpose behind controlling the drug delivery is to achieve more effective therapies while eliminating the potential for both, under and overdosing. A range of materials have been employed to control the release of drugs and other active agents. The earliest of these polymers were originally intended for other, nonbiological uses and were selected because of their desirable physical properties, for example: l Poly (urethanes) for elasticity. l Poly (siloxanes) or silicones for insulating

ability. l Poly (methyl methacrylate) for physical strength

and transparency. l Poly (vinyl alcohol) for hydrophilicity and

strength. l Poly (ethylene) for toughness and lack of

swelling. l Poly (vinyl pyrrolidone) for suspension

capabilities.

To be successfully used in controlled drug delivery formulations, a material must be chemically inert and free of leachable impurities. It must also have an appropriate physical structure, with minimal

undesired aging and be readily processable. Some of the materials that are currently being used or studied for controlled drug delivery include, Poly(2-hydroxy ethyl methacrylate), Poly(N-vinyl pyrrolidone), Poly(methyl methacrylate), Poly(vinyl alcohol), Poly(acrylic acid), Poly(acrylamide), Poly(ethylene-co-vinyl acetate), Poly(ethylene glycol) and Poly(methacrylic acid).

However, in recent years additional polymers designed primarily for medical applications have entered the arena of controlled release. Many of these materials are designed to degrade within the body, among them include Polylactides (PLA), Polyglycolides (PGA), Poly(lactide-co-glycolides) (PLGA), Polyanhydrides and Polyorthoesters.

Originally, polylactides and polyglycolides were used as absorbable suture materials and it was a natural step to work with these polymers in controlled drug delivery systems.

The greatest advantage of these degradable polymers is that they are broken down into biologically acceptable molecules that are metabolised and removed from the body via normal metabolic pathways.

Diffusion MechanismThere are three primary mechanisms by which active agents can be released from a delivery system: diffusion, degradation and swelling followed by diffusion.

Any or all these mechanisms may occur in a given release system. Diffusion occurs when a drug or other active agent passes through the polymer that forms the controlled-release device.

The diffusion can occur on a macroscopic scale through pores in the polymer matrix or on a molecular level by passing between polymer chains.

Examples of diffusion-release systems are shown in Figures 1 and 2. In Figure 1, a polymer and active agent have been mixed to form a homogeneous system, also referred to as a matrix

A major but defining difference between polymers and biopolymers can be found in their structures. Polymers, including biopolymers, are made of repetitive units called monomers.

Figure 1: Drug delivery from a typical matrix drug delivery system.

Time


system. Diffusion occurs when the drug passes from the polymer matrix into the external e n v i r o n m e n t . As the release continues, its rate normally decreases with this type of system, since the active agent has

a progressively longer distance to travel and therefore requires a longer diffusion time to release.

For the reservoir systems shown in Figures 2a and 2b, the drug delivery rate can remain fairly constant. In this design, a reservoir whether solid drug, dilute solution or highly concentrated drug solution within a polymer matrix is surrounded by a film or membrane of a rate-controlling material. The only structure effectively limiting the release of the drug is the polymer layer surrounding the reservoir.

Since this polymer coating is essentially uniform and of a nonchanging thickness, the diffusion rate of the active agent can be kept fairly stable throughout the lifetime of the delivery system. The system shown in Figure 2a is representative of an implantable or oral reservoir delivery system, whereas the system shown in Figure 2b illustrates a transdermal drug delivery system, in which only one side of the device will actually be delivering the drug.

Once the active agent has been released into the external environment, for transdermal drug delivery, the penetration of the drug through the skin constitutes an additional series of diffusion and active transport steps, as shown

schematically in Figure 3.

For the diffusion-controlled systems described thus far, the drug delivery device is fundamentally stable in the b i o l o g i c a l

environment and does not change its size either through swelling or degradation.

In these systems, the combinations of polymer matrices and bioactive agents chosen must allow for the drug to diffuse through the pores or macromolecular structure of the polymer upon introduction of the delivery system into the biological environment without inducing any change in the polymer itself14-15.

Controlled and targeted drug release is one of the most important areas for research with broad implications in many areas of medicine and biopolymers. Biopolymers play an important role for drug delivery as it can be design as per their solubility with respect to pH, temperature and other stimulus. Many drugs are difficult to control as they must be delivered over a prolonged period to have a beneficial effect.

Hydrophobic drugs are very difficult to control as they are not soluble in water. So, they do not transport to the different parts of the body and require more attention towards the drug delivery system namely,l Controlled drug releasel Targeted drug deliveryl Hydrophobic drug deliveryl Tissue specific delivery system

Controlled Drug Release Controlled-release is a perfectly zero-order release, that is, the drug releases over time irrespective of concentration.

Stiff gels are an example of reduced diffusion rates; as a consequence, drugs dissolved within a gel network tend to be released slowly. Ma Y et al have studied the drug release behaviour of DPA-MPC-DPA triblock copolymer gel loaded with dipyridamole which can be tuned by changing either the copolymer concentration or the solution pH[1].

Targeted Drug DeliveryHydrophobic Drug DeliveryHydrophobic drugs are very difficult to control as they are not soluble in water. Due to this they are not transported to different parts of the body and thus require more attention.

To overcome this problem, the drugs are hidden

Figure 2: Drug delivery from typical reservoir devices: (a) implantable or oral systems and (b) transdermal systems.

It is also possible for a drug delivery system to be designed in such a manner that it is incapable of releasing its agent or agents until it is placed in an appropriate biological environment.


within the larger host biopolymer matrix, which is soluble in water or has stimulus responsive behaviour. Such type of drugs can be a host within the hyperbranched polymers or in dendrimers, a variety of small hydrophobic molecules, such as drugs, within their hydrophobic interior. Flow microcalorimetry analysis (using an antifungal agent/dendrimer complex) against a suspension of Saccharomycees sp have further demonstrated that the drug is released upon contact between the dendrimer and the biological cell.

Tissue Specific Delivery SystemSynthetic water-soluble polymeric delivery systems have been developed to allow selective delivery of therapeutic and imaging agents to musculoskeletal tissues. For mineralised tissues, bone-targeting agents such as aspartic acid octapeptide could concentrate the polymer conjugates to bone surfaces including resorption sites, which was demonstrated with routine bone histomorphometry2.

Environmentally Responsive SystemsIt is also possible for a drug delivery system to be designed in such a manner that it is incapable of releasing its agent or agents until it is placed in an appropriate biological environment.

Swelling-controlled release systems are initially dry and when placed in the body, will absorb water or other body fluids and swell. The swelling increases the aqueous solvent content within the formulation as well as the polymer mesh size, enabling the drug to diffuse through the swollen network into the external environment. Examples of these types of devices are shown in Figure 4 (a and b) for reservoir and matrix systems, respectively. Most of the

materials used in swelling-controlled release systems are based on hydrogels, which are polymers that will swell without dissolving when placed in water or other biological fluids. These hydrogels can absorb a great deal of fluid and at equilibrium, typically comprise 60–90% fluid and only 10–30% polymer. The polymer swelling can be triggered by a change in the environment surrounding the delivery system. Depending upon the polymer, the environmental change can involve pH, temperature or ionic strength and the system can either shrink or swell upon a change in any of these environmental factors.

Such materials are ideal for systems such as oral delivery, in which the drug is not released at low pH values in the stomach, but rather at high pH values in the upper small intestine.

Biodegradable SystemsMost biodegradable polymers are designed to degrade as a result of hydrolysis of the polymer chains into biologically acceptable and progressively smaller compounds for example, polylactides and polyglycolides. Degradation may take place through bulk hydrolysis, in which the polymer degrades in a fairly uniform manner throughout the matrix. For some degradable polymers, most notably the polyanhydrides and polyorthoesters, the degradation occurs only at the surface of the polymer, resulting in a release rate that is proportional to the surface area of the drug delivery system. The most common formulation for these biodegradable materials is that of microparticles, which have been used in oral delivery systems and even more often, in subcutaneously injected delivery systems.

Biopolymers in PackagingThree main biopolymers constitute less than 90% of the biopolymer market of packaging (2008). Starch/ starch blends, PLA, cellulose starch based biopolymers dominate the market (75-80%) because they are economical and competitive to petrochemical materials. The properties of starch that make it preferable in this market are hydrophilic, brittle, relatively easy to process and vulnerable to degradation.

The other polymer PLA is also dominating Figure 4: Drug Delivery from a) Matrix b) Swelling –controlled release systems.

Controlled and Targeted drug release is one of the most important areas for research with broad implications in many areas of medicine and biopolymers.


l Synthetic polymers such as PLA, PGA, PLGA, PCL, Polyorthoesters, Poly (dioxanone), Poly (anhydrides), Poly (trimethylene carbonate) and Polyphosphazenes.

The medical applications of biopolymers can be summarised as:

l Wound management such as sutures, staples, clips, adhesives and surgical meshes.

l Orthopaedic devices such as pins, rods, screws, tacks, ligaments etc.

l Dental applications guided tissue regeneration membrane, void filler following tooth extraction.

l Cardiovascular applications stents.

l Intestinal applications anastomosis rings.

l Drug delivery system.

l Tissue engineering.

Biopolymers in Agriculture FieldAgricultural applications for biopolymers are not limited to film covers. Containers such as biodegradable plant pots and disposable composting containers and bags are made of biopolymers. Fertilizer and chemical storage bags which are biodegradable are also made of biopolymers. Young plants which are particularly susceptible to frost may be covered with a thin Ecoflex film. At the end of the growing season, this film can be worked back into the soil, where it will be broken down by the appropriate micro organisms.

Therefore, plastic films that begin to degrade in average soil conditions after approximately one month are ideal candidates as crop mulches1.

EVOHChitosan/glycerol

PVDCPARAGON

Amylopectin/glycerol (10:4)Whey/glycerol

Amylose/glycerol (10:4)PA6

Wheat gluten/glycerolPHAPLA

EcoflexLDPE

0 1 2 3 4 5 6 7

Log OTR (cm3 µm/m2 d bar)

PVDC

LDPE

PHA

PLA

PA6

Ecoflex

Ricestarch/PE blend (20/80)

Wheat gluten/glycerol

Whey/glycerol

Chitosan/glycerol

PARAGON

EVOH

-5 -4 -3 -2 -1 -0

Log WVT (g/m2/d)

Tendon

Nucleus offibroblast

Collagenfibres

Containers such as biodegradable plant pots and disposable composting containers and bags are made of biopolymers.

the packaging field because it has high transparency, high gloss and low haze, low heat deflection temperature (HDT) and high heat seal strength (good performance in film sealing).

Cellulose, on other hand, is hydrophilic/ water vapour sensitive film. It has good mechanical properties (in dry state), not thermoplastic or sealable and also has good oxygen barrier (in dry state).

A graphical comparison of OTR and WVTR properties of polymers and biopolymers is given in figure 5.

Biopolymers in Medical FieldBiodegradable polymers generally being used for medical applications include:

l Natural polymers such a Fibrin, Collagen, Chitosan, Gelatin and Hyaluronan.


Nan BiomaterialsCollagensThey are natural biopolymers and make up ~25% of total protein mass in mammals. Collagen comprises of 25 isoforms and exist in large quantity in extracellular matrix of skin, bone, tendon, cartilage and other connective tissues for support and protection. Collagen fibres withstand high pulling forces. Elastic modulus is ~1 GPa. It takes 10 kg to rupture a fibre of 1 mm.

ElastinsElastic fibres permit long-range deformability and passive recoil. Elastic modulus is ~0.1 MPa. Their functioning is crucial for arteries, lung, skin and other dynamic connective tissues that undergo cycles of extension and recoil.

The major component of elastic fibres is the thread-like protein elastin. Fibrillins provide an outer structure for amorphous, cross-linked elastin. During ageing, elastin is degraded and becomes inflexible.

ProteoglycansThey are a diverse group of proteins with multiple polysaccharide chains and found in connective tissues and extracellular matrix. They are also attached to the surface of many cells and constitute a major portion of extracellular matrix. They are highly hydrated.

Alginic acidAlginic acid, also called algin or alginate, is an anionic polysaccharide distributed widely in the cell walls of brown algae, where it, through binding water, forms a viscous gum. In extracted form, it absorbs water quickly; it is capable of absorbing 200-300 times its own weight in water. Its colour ranges from white to yellowish-brown. It is sold in filamentous, granular or powdered form. Its molecular formula is (C6H8O6)n and its density is 1.601 g/cm3. It is used as an additive in dehydrated products such as slimming aids and in the manufacture of paper and textiles as well as in waterproofing and fireproofing fabrics, as a gelling agent, for thickening drinks, ice cream and cosmetics and as a detoxifier that can absorb poisonous metals from the blood. It is used extensively as an impression-making material in dentistry, prosthetics, life casting and

occasionally for creating positives for small-scale casting5.

ConclusionToday, biobased polymers are gaining importance because conventional resources. In the days to come, more and more stress will be exerted on such ecofriendly sources so as to save our environment.

References1. Biodegradable Polymers: Past, Present and Future

M. Kolybaba, L.G. Tabil, S. Panigrahi, W.J. Crerar, T. Powel, B. Wang, Department of Agricultural and Bioresource Engineering University of Saskatchewan, 57Campus Drive, Saskatoon, SK, CANADA S7N 5A9.

2. Biodegradable Plastics: Amanda Libbie Kelebit Technology Park Malaysia College.

3. Innovating Packaging Solutions for Fresh Fish: Marit Kvalvåg Pettersen, Anlaug Ådland Hansen, Nofima Food, Matforsk, Norway.

4. Biobased packaging materials for the food industry : Types of Biobased Packaging Materials : Dr. Semih Ötles – Serkan Ötles.

5. Extracellular Matrix: 01/07, Boris Hinz, PhD.

6. Molecules of Life: Biopolymers, Dr. Dale Hancock,[email protected].

7. Rebirth of Bio-based Polymer Development : Dr. Shelby F. Thames The University of Southern Mississippi.

8. Green Chemistry Education, Application and Latest Development : Michael H. W. Lam Department of Biology and Chemistry, City University of Hong Kong.

9. Biodegradable Polymers and Sustainability: Insights from Life Cycle Assessment: Richard Murphy, Imperial College London and Ian Bartle on behalf of the National Non-Food Crops Centre.

10. Environment and Plastics Industry Council:Technical Report;Biodegradable Polymers, a review.

11. Biodegradable Polymers; by R Chandra et al, Prog. Polym. Sci., Vol. 23, 1273-1335, 1998.

12. Biodegradable polymers produced by mixed cultures from renewable sources: Luísa Seuanes Serafim, Biochemical Engineering and Processes Group, CQFB-Requimte FCT/Universidade Nova de Lisboa.

13. Polymeric systems for Controlled drug release: Uhrich KE, Chem Rev 1999, 99.3181-3198.

14. D. L. Wise: Handbook of Pharmaceutical Controlled Release Technology. Marcel Dekkar Inc., New York and Basel,2000.

15. Polymer in drug delivery, Omathanu Pillai and Ramesh Panchagnula, Current Opinion in Chemical Biology, Vol.5 Issue 4, 2001, Pages 447-451.

Documents

Biopolymers Efficient Drug Delivery