BIODEGRADABLE POLYMERS

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BIODEGRADABLE POLYMERS:

BIODEGRADABLE POLYMERS

CONTENTS:

CONTENTS Introduction Definition Characteristics of biodegradable polymers in drug delivery system Classification of biodegradable polymers Factors affecting biodegradation of polymers Advantages of biodegradable polymers Applications of biodegradable polymers Conclusion References

INTRODUCTION:

INTRODUCTION Polymer Polymers are defined as very large molecules consisting of many repeating units & are formed by a processes called polymerization , which links together smaller molecules known as monomers. Monomers can be linked together in various ways to give ……… Linear Branched cross linked polymers

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Based on biodegradability polymers are classified as: 1. Biodegradable polymers eg : collagen, poly glycolic acid etc., 2. Non biodegradable polymers eg : poly vinyl chloride, polyethylene etc.,

BIODEGRADABLE POLYMER :

BIODEGRADABLE POLYMER Definition : D efined as polymers comprised of monomers linked to one another through functional groups and have unstable links in the backbone . Broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways .

IDEAL CHARACTERISTICS:

IDEAL CHARACTERISTICS Inert Permeability Biodegradability Bio- compatilibility Tensile strength

CLASSIFICATION:

CLASSIFICATION Based on mechanism of release of drug Based on type of degradation Based on the source

1.Based on the mechanism of release: :

1.Based on the mechanism of release: Slow dissolution and erosion by hydrolysis Water insoluble polymers degradation of pendent group without backbone cleavage. Water insoluble polymer degrades to water-soluble products by backbone cleavage

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H2O soluble Swelling Dimensional stability H2O insoluble Chemical change No backbone cleavage H 2 O insoluble Chemical cleavage MW↓

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BIODEGRADATION ENZYMATIC DEGRADATION COMBINATION HYDROLYSIS BULK EROSION SURFACE EROSION Mechanism Of Biodegradable Polymers

2. Based on type of degradation :

2 . Based on type of degradation Bioerosion – which contains both physical (dissolution) and chemical (backbone cleavage) process. Chemical degradation

Types of bioerosion:

Types of bioerosion Bulk erosion Surface erosion Bulk erosion: Degradation takes place through out the whole of the sample Ingress of water is faster than the rate of degradation Eg : Polylactic acid (PLA) Polyglycolic acid (PGA)

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Surface erosion Sample is eroded from the surface Mass loss is faster than the ingress of water into the bulk Eg : Polyanhydrides , polyorthoesters

Chemical degradation :

Chemical degradation Chemical degradation - mediated by water , enzymes , microorganisms CLEAVAGE OF CROSSLINKS TRANSFORMATION OF SIDE CHAINS CLEAVAGE OF BACKBONE

3.Based on the source :

3.Based on the source Synthetic biodegradable polymers: eg : Aliphatic poly(esters) Polyanhydride P olyphosphazene Pseudo poly aminoacid P oly( orthoesters ) etc., Natural biodegradable polymers: eg : Albumin C ollagen G elatin etc.,

Synthetic biodegradable polymers:

Synthetic biodegradable polymers Aliphatic poly(esters) These are prepared by ring opening and polymerization of cyclic ester. Aliphatic polyesters include: POLY (GLYCOLIC ACID) ---(--O—C-CH 2 ---) n POLY (LACTIC ACID) --(--O---C—CH---) n POLY (CAPROLACTONE) --(--O—C---(CH 2 ) 5 ---) n

Lactide /glycolide polymers: :

Lactide / glycolide polymers: Most widely used biodegradable polymers Lactide / glycolide are the simplest aliphatic polyester Biodegradation : Undergo biodegradation by bulk erosion. Cleaved by hydrolysis to monomeric acids and eliminated through kreb’s cycle. Enzymatic degradation is also reported.

Applications :

Applications Used to deliver drugs in the form of microspheres , implants etc., Examples of drugs delivered include steroid hormones, antibiotics, anti cancer agents etc.,

Poly ε caprolactone:

Poly ε caprolactone semi-crystalline polymer slower degradation rate than PLA remains active as long as a year for drug delivery Biodegradation: Occurs in two phases: First phase: hydrolytic chain scission of the ester linkage Second phase: decrease in the rate of chain scission and onset of weight loss due to: Diffusion of small mol wt polymer Breakup of polymer mass to produce smaller particles

Applications: :

Applications: Drug delivery applications of PCL includes: - Cyclosporin in the form of nanoparticles - Ciprofloxacin in the form of dental implants

Poly anhydrides:

Poly anhydrides Compression and injection moulding methods are employed to formulate matrices bearing drug. B iodegradation: Degrades by surface erosion Carboxylic anhydride bond in the polymer chain is responsible for fast erosion. Degradation is faster in basic than acidic media.

Applications: :

Applications: Suitable for short term drug delivery Used for vaccination and localized tumor therapy.

polyphosphazenes:

polyphosphazenes Hydrolytic stability/instability is determined by change in side group attached to macromolecular backbone. Based on side chain these are of 3 types: Hydrophobic phosphazenes Hydrophilic phosphazenes Amphiphilic phosphazenes

Applications: :

Applications: Used in the construction of soft tissue prosthesis, tissue like coatings, as material for blood vessel prosthesis. Used for immobilization of antigen or enzyme

Poly orthoesters:

Poly orthoesters These have acid- labile linkages in their backbone. Acid excipents causes fast erosion whereas basic excipients causes long term erosion. Application: Used in contraceptive steroid bearing bioerodible polymer

Natural biodegradable polymers:

Natural biodegradable polymers Natural polymers are an attractive class of biodegradable polymers as they are: Derived from natural sources Easily available Relatively cheap

collagen:

collagen Prime function is to check tissue deformation and avoid mechanical failure. Advantages: It is a major structural protein in animals It is used as sutures ,Dressings, etc. Readily isolated & purified in large quantities. Can be processed in variety of forms .

Cont…:

Cont… Disadvantages Poor dimensional stability. Variability in drug release kinetics. Poor mechanical strength. Application: Majorly used in ocular drug delivery system

Albumin:

Albumin It is a major plasma protein component. It accounts for more than 55% of total protein in human plasma. It is used to design particulate drug delivery systems.

Cont…:

Cont… Factors Affecting Drug Release From Albumin Microspheres Physicochemical properties and the concentratio n of the drug. Interaction between the drug and the albumin matrix. Size and density of microspheres. Nature and degree of cross-linking . Presence of the enzymes and pH in the environment .

Application: :

Application: Albumin micro-spheres are used to deliver drugs like Insulin, Sulphadiazene , 5-fluorouracil, Prednisolone etc. It is mainly used in chemotherapy , to achieve high local drug concentration for relatively longer time.

Gelatin:

G elatin Heterogeneous products obtained by hydrolytic extraction of treated animal collagen. Physicochemical properties depends on the source of collagen, extraction method and thermal degradation. Applications : Employed as matrix and as coating material. Gelatin micropellets are used for oral controlled delivery of drugs.

Dextran :

Dextran Dextran is a complex branched polysaccharide made of many glucose molecules joined into chains of varying lengths. It consists of α-D-1,6-glucose-linked glucan with side-chains linked to the backbone of Polymer. Mol.wt ranges from 1000 to 2,00,000 Daltons Applications : Used for colonic delivery of drug in the form of gels

FACTORS AFFECTING BIODEGRADATION OF POLYMERS:

FACTORS AFFECTING BIODEGRADATION OF POLYMERS Morphology factors Shape & size Variation of diffusion coefficient and mechanical stresses Chemical factors Chemical structure & composition Presence of ionic group and configuration structure Molecular weight and presence of low molecular weight compounds Physical factors Processing condition Sterilization process

ADVANTAGES OF BIODEGRADABLE POLYMERS:

ADVANTAGES OF BIODEGRADABLE POLYMERS Localized delivery of drug Sustained delivery of drug Stabilization of drug Decrease in dosing frequency Reduce side effects Improved patient compliance Controllable degradation rate

APPLICATIONS OF BIODEGRADABLE POLYMERS:

APPLICATIONS OF BIODEGRADABLE POLYMERS Polymer system for gene therapy Biodegradable polymer for ocular, tissue engineering, vascular, orthopedic, skin adhesive & surgical glues. Bio degradable drug system for therapeutic agents such as anti tumor, antipsychotic agent, anti-inflammatory agent.

BIODEGRADABLE POLYMERS IN ADVANCED DRUG DELIVERY:

BIODEGRADABLE POLYMERS IN ADVANCED DRUG DELIVERY POLYMERIC MICELLES: used to deliver therapeutic agents. HYDRO GELS: these are currently studies as controlled release carriers of proteins & peptides. The polymer matrix can be formulated as either micro/ nano -spheres, gel, film or an extruded shape. The shape of polymer can be important in drug release kinetics .

Conclusion:

C onclusion Numerous synthetic biodegradable polymers are available and still being developed for sustained and targeted drug delivery applications. Biodegradable polymers have proven their potential for the development of new, advanced and efficient DDS and capable of delivering a wide range of bioactive materials. However, only few have entered the market since many drugs faces the problem of sensitivity to heat, shear forces and interaction between polymers. These problems can be overcome by fully understanding the degradation mechanism to adjust the release profile.

References:

R eferences Controlled and Novel D rug D elivery by N. K. Jain; pg no: 27-51. Controlled Drug D elivery C oncepts and Advances by S.P.Vyas Roop K.Khar ; pg no:97-155. Novel Drug Delivery Systems by Yie W Chien ; second edition; pg no:32-34. Design of Controlled Release Drug Delivery System by Xiaoling Li, Bhaskara R. Jasti ; pg no:271-303. International Journal of Pharma Research and Development; volume 2; issue8(002). Advanced Drug Delivery reviews;56(2004);pg no: 1453-1466 by Gesine winzenburg et. al.

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