biodegradable polymers

Prepared by:Malay N. JivaniM. pHarm sem 1. (ceutics)Sub : PFD

BIODEGRADABLE POLYMERS

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Malay N.Jivani

CONTENTS:

Introduction To Polymers Definition and Ideal Characteristics of biodegradable

polymersFactors Influence the Degradation BehaviorDegradation MechanismsMethods of Studying Polymer DegradationGeneral Medical Applications of Biodegradable PolymersClassification of biodegradable polymersAdvantages of biodegradable polymers Biodegradable polymer in Advanced Drug Delivery Conclusion References

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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:

Biodegradable polymers eg : collagen, poly glycolic acid etc.,

Non biodegradable polymers eg : poly vinyl chloride, polyethylene

etc

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BIODEGRADABLE POLYMER :

Definition : Defined 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 .

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IDEAL CHARACTERISTICS:

Inert PermeabilityBiodegradability Bio- compatilibility Tensile strength

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Factors Influence the Degradation Behavior

Chemical Structure and Chemical Composition Distribution of Repeat Units in Multimers Molecular Weight Polydispersity Presence of Low Mw Compounds (monomer, oligomers, solvents, plasticizers, etc) Presence of Ionic Groups Presence of Chain Defects Presence of Unexpected Units Configurational Structure Morphology (crystallinity, presence of microstructure, orientation and residue

stress) Processing methods & Conditions Method of Sterilization Annealing Storage History Site of Implantation Absorbed Compounds Physiochemical Factors (shape, size) Mechanism of Hydrolysis (enzymes vs water)

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Degradation Mechanisms

Enzymatic degradationHydrolysis

(depend on main chain structure: anhydride > ester > carbonate)

Homogenous degradation Heterogenous degradation

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Degradation can be divided into 4 steps:

Water sorptionReduction of mechanical properties (modulus &

strength)Reduction of molar massWeight loss

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Degradation Schemes

Surface erosion (poly(ortho)esters and polyanhydrides) Sample is eroded from the surface Mass loss is faster than the ingress of water into the

bulk

Bulk degradation (PLA,PGA,PLGA, PCL) Degradation takes place throughout the whole of the

sample Ingress of water is faster than the rate of degradation

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Factors That Accelerate Polymer Degradation

More hydrophilic backbone. More hydrophilic endgroups. More reactive hydrolytic groups in the backbone. Less crystallinity. More porosity. Smaller device size.

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Methods of Studying Polymer Degradation

Morphological changes (swelling, deformation, bubbling, disappearance…)

Weight lose Thermal behavior changes

Differential Scanning Calorimetry (DSC) Molecular weight changes

Dilute solution viscosity Size exclusion chromatograpgy(SEC) Gel permeation chromatography(GPC) MALDI mass spectroscopy

Change in chemistry Infared spectroscopy (IR) Nuclear Magnetic Resonance Spectroscopy (NMR) TOF-SIMS

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General Medical Applications of Biodegradable Polymers

Wound management • Sutures• Staples• Clips• Adhesives• Surgical meshes

Orthopedic devices• Pins• Rods• Screws• Tacks• Ligaments

Dental applications• Guided tissue

regeneration Membrane

• Void filler following tooth extraction

Cardiovascular applications • Stents

Intestinal applications• Anastomosis rings

Drug delivery systemTissue engineering

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Why Would a Medical Practitioner Like a Material to Degrade in the Body?

Do not require a second surgery for removal

Avoid stress shielding

Offer tremendous potential as the basis for controlled drug delivery

BONE+PLATE

BONE PLATE

Time

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Degradable Polymer Plate

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Biodegradable Polymers Used for Medical Applications

Natural polymers Fibrin Collagen• Chitosan Gelatin Hyaluronan

Synthetic polymers PLA, PGA, PLGA, PCL, Polyorthoesters … Poly(dioxanone) Poly(anhydrides) Poly(trimethylene carbonate) Polyphosphazenes

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CLASSIFICATION:

Based on mechanism of release of drug

Based on type of degradation Based on the source

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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

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

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2. Based on type of degradation :

which contains both physical (dissolution) and chemical (backbone cleavage) process. Chemical degradation

Mechanism Of Degradation BioerosionSurface erosion Chemical Degradation

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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)

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

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Chemical degradationmediated by water , enzymes , microorganisms Cleavage of cross-links transformation of side chains cleavage of backbone

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3. Based on Source:

Synthetic biodegradable polymers eg : Aliphatic poly(esters)

Polyanhydride Polyphosphazene

Pseudo polyaminoacid Poly( orthoesters ) etc.,

Natural biodegradable polymers: eg : Albumin

Collagen Gelatin etc.,

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Example of Some (Natural) Biodegradable Polymers:

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 .

Disadvantages Poor dimensional stability. Variability in drug release kinetics. Poor mechanical strength.

Application: Majorly used in ocular drug delivery system

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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.

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.

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Gelatin: 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.

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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

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Example of Some (Synthetic) Biodegradable 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 : Used to deliver drugs in the form of microspheres , implants etc., Examples of drugs delivered include steroid hormones, antibiotics, anti cancer agents etc.,

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

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

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

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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

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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

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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 .

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Conclusion:

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.

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References:

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

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biodegradable polymers

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