Biodegradable natural polymers (2)

1. Biodegradable Natural Polymers Prepared by: (Group B) Ajay Shah Bhaskar Shrestha Eroj Yemi Manisha Shrestha Prakriya Shrestha Rajiv Dangol Sajan Maharjan Tripti Amatya

2. S.No Topics Name Date 1 Introduction Tripti Amatya 19 th to 21 nd January 2014 2 Gelatin Manisha Shrestha 3 Prakriya Shrestha 4 Chitosan Bhaskar Shrestha 5 Eroj Yemi 6 Hyaluronic Acid Rajiv Dangol 7 Sajan Maharjan 8 Conclusion & Compilation Ajay Shah Log Book Discussion on Topic : Tuesday; 14 January, 2014 Internet Survey : Wednesday to Friday; 15 to 17 January, 2014 Work Division : Saturday; 18 January, 2014 Disscussion and Modification of Assignment : Wednesday to Saturday; 22 to 25 January, 2014 Preparation of Presentation : Friday to Sunday; 24-26 th January, 2014

3. Introduction Polymer Definition Also known as macro-molecules.

4. Biodegradation Biodegradation is the process of converting polymer material into harmless, simple, gaseous products by the action of enzymes, micro-organisms and water . Biodegradable Polymer Biodegradable polymers degrade as a result of natural biological processes, eliminating the need to create a disposal system which can cause harm to our environment. BIODEGRADATION ENZYMATIC DEGRADATION COMBINATION HYDROLYSIS BULK EROSION SURFACE EROSION Mechanism Of Biodegradable Polymers

5. ENZYMATIC DEGRADATION

6. Need for Biodegradable polymer 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 Mechanical Strength Degradable Polymer Plate

7. NATURAL POLYMERS These are the polymers obtained from natural resources, and are generally non-toxic . Natural polymers are formed in nature during the growth cycles of all organisms . NATURAL POLYMERS PROTEINS Polysaccharides Eg : COLLAGEN ALBUMIN FIBRIN Eg : DEXTRAN CHITOSAN STARCH ADVANTAGES : Readily & Abundantly Available . Comparatively Inexpensive. Non toxic products. Can be modified to get semi synthetic forms .

8. Classification of Natural biodegradable polymers (Based on Origin) Plant Animal Microbes Polysaccharides Eg : Cellulose, Starch, Alginate Proteins Eg : Collagen (Gelatin), Albumin Polysaccharides Eg : Chitin (Chitosan), Hyaluronate Polyesters Eg : Poly(3-hydroxylalkonate) Polysaccharides Eg : Hyaluronate

9. Chitosan : Introduction Chitin is a macromolecule found in the shells of crabs, lobsters, shrimps and insects Chitosan is obtained by partial deacetylation of chitin. Chitin is insoluble in its native form but chitosan , the partly deacetylated form, is water soluble.

10. Chemistry linear co-polymer of β (1-4) linked glucosamine and N-acetyl-D-glucosamine.

11. Extraction of chitosan Crustacean shells (containing chitin) De colorization Dil. NaOH Dil. HCl Deproteinization Deacetylation ( chitosan ) Demineralization 0.5% KMnO 4 and oxalic acid Hot Conc. NaOH (40-50%)

12. Physiochemical properties Odorless, white or creamy-white powder Chelates many transitional metal ions Highly basic polysacharides in acidic pH, it gets solubilized due to protonation of free amino groups and the resultant soluble polysaccharide is positively charged. hydrophilic in nature thereby it has the ability to form gels at acidic pH. Degraded by lysozyme to it’s by products glucosamine and n-acetyl glucosamine

13. Application Ocular delivery: making contact lens- optical clarity, sufficient optical correction, gas permeability, particularly towards oxygen, wettability and immunological compatibility . antimicrobial and wound healing properties of chitosan along with an excellent film capability make chitosan suitable for development of ocular bandage lenses. Colon drug delivery: Degraded by microflora present in human colon which supports colon drug delivery Coating material: Good film forming property and mucoadhesive property

14. Mucosal delivery: Chitosan gets protonated in acidic solution, so it binds strongly to negatively charged cell surface making it useful to formulate bioadhesive dosage forms. Transdermal drug delivery: Studies on propranolol hydrochloride (prop- HCl ) delivery systems using various chitosan membranes with different crosslink densities as drug release controlling membranes and chitosan gel as the drug reservoir have been performed. Gene Delivery : Chitosans , typically isolated from the shell of shrimp, has the ability to react with DNA and compact it to produce a nanoparticle . Such nanoparticles are more readily taken up by cells. Others: nano band- aid,cosmetics , etc.

15. Hyaluronic acid:Introduction Carbohydrate polyanionic mucopolysacharide , occurring naturally in all living organisms. Can be several thousands of sugar long One of most hydrophiic molecules, also known as natural moisturizer Generally found in sodium salt form i.e. as sodium hyaluronate

16. Biosynthesis of HA in Bacillus subtilis UDP- glucoronic acid HYALURONIC ACID UDP-N- acetylglucosamine Hyaluronan synthase Pentose phosphate pathway Glycolysis UDP UDP HA is naturally synthesized from addition of glucoronic acid and N- acetylglucosamine to growing chain using their activated nucleotide sugars. Hyaluronan synthase is the enzyme responsible.

17. Structure and chemistry P olysaccharide made up of largely repeating disaccharide units The alternating disaccharide units are linked by (1→4) inter glycosidic linkage. Chains consist upto 30,000 repeating units so it has high molecular weight range (1000 to 10,000,000 Da ).

18. Properties Biodegradable, biocompatible, non-toxic, non- immunogenic, non-inflammatory, linear chain polysaccharide very hydrophilic; it adsorbs water making it hygroscopic readily soluble in water, and produces a gel Its viscous solutions have most unusual rheological properties ( pseudoplasticity ) and are exceedingly lubricious To improve the mechanical properties and control the degradation rate, HA can be chemically modified or crosslinked to form a hydrogel of the gel is dependent upon a number of factors including the length of the chain, cross-linking, pH

19. Application They are used in the preparation of gels for delivery of drugs to eye and installation into other cavities. Microparticulate HA carrier: Sustained-release formulations ( eg : protein drugs) have been developed using spray-dried HA microparticles which act as a protein reservoir Also protects the drugs from denaturation and increases their bioactivity Ocular drug delivery : Its viscosity and pseudoplastic behavior which provide mucoadhesive property can increase the ocular residence time

20. Cell targetting : The expression of CD-44 (cluster determinant 44) and RHAMM (receptor for hyaluronate -mediated motility) receptors by various tumour cells, which are endogenous ligands for HA, makes this a good candidate for drug targeting to cancer cells Nasal delivery : A nanocarrier composed of hyaluronic acid(HA) and chitosan (CH) was reported to encapsulate bovine serum albumin (BSA) and cyclosporine A for the nasal delivery of macromolecules Topical drug delivery : Surface hydration and film formation enhance the permeability of the skin to topical drugs also promotes drug retention and localization in the epidermis

21. HA has been used in tissue engineering for the cartilage replacement in the joints Used in cosmetics, skin care system, as anti ageing therapy (antioxidant nature)

22. GELATIN-INTRODUCTION Gelatin is a natural water soluble functional polymer (protein) that is derived by partial hydrolysis of collagen (chief protein component in skin, bones and white connective tissues of the animal body). It is commonly used for pharmaceutical and medical applications because of its biodegradability and biocompatibility in physiological environments. Gelatin does not occur free in nature, and derived from chief protein component in skin, bones, hides, and white connective tissues of the animal body is classified as a derived protein

23. GELATIN-TYPES Gelatin derived from an acid-treated precursor is known as Type A and gelatin derived from an alkali-treated process is known as Type B. Results in a difference in isoelectric points, being 7 – 9 for gelatin type A and 4 – 5 for gelatin type B.

24. FEATURES OF GELATIN Characteristic features of gelatin are the high content of the amino acids glycine, proline (mainly as hydroxyproline ) and alanine . Gelatin molecules contain repeating sequences of glycine, proline and alanine amino acid triplets , which are responsible for the triple helical structure of gelatin.

25. STRUCTURE OF GELATIN The chemical structure of gelatin is what makes gelatin water soluble; form digestible gels and films that are strong, flexible, and transparent; and form a positive binding action that is useful in food processing,pharmaceuticals , photography,and paper production.

26. MFG OF GELATIN

27. PHYSICAL PROPERTIES Tasteless and odorless Vitreous, brittle solid, yellow colored Moisture content: 8-13% ; Relative density of: 1.3-1.4 Formation of thermo-reversible gels in water: When gelatin granules are soaked in cold water they hydrate into discrete, swollen particles. On being warmed, these swollen particles dissolve to form a solution.

28. CHEMICAL PROPERTIES Soluble in aqueous solutions of polyhydric alcohols such as glycerol and propylene glycol. Insoluble in less polar organic solvents such as benzene, acetone, primary alcohols and dimethylformamide . Gelatin stored in air-tight containers at room temperature remains unchanged for long periods of time. When dry gelatin is heated above 45° C in air at relatively high humidity (above 60% RH) it gradually loses its ability to swell and dissolve. Sterile solutions of gelatin when stored cold are stable indefinitely; but at elevated temperatures the solutions are susceptible to hydrolysis. Gelatin is composed of 50.5% carbon, 6.8% hydrogen, 17% nitrogen and 25.2% oxygen. It gives typical protein reactions and is hydrolyzed by most proteolytic enzymes to yield its peptide or amino acid components.

29. Application of Gelatin in pharmaceutical formulation and drug delivery Two-Piece Hard Capsules Soft Elastic Gelatin Capsules As a binder in Tablet Tablet Coating Suppositories Gelatin Emulsions Microencapsulation Source of essential amino acids Absorbable Gelatin Sponge Gelatin as Nanoparticle.

30. CONCLUSION Biodegradable polymers have received much more attention in the last decades due their potential applications in the field of pharmaceuticals. Biodegradable polymers have been researched, but polymers based on renewable sources (especially on starch) are most desirable. It provides a drug at a constant controlled rate owes a prescribed period of time; cell targeting, colon targeting and nasal drug delivery system and also assist in gene therapy. It would degrade into nontoxic, absorbable subunits which would be subsequently metabolized and removed from the body . Recently different studies have been reported concerning the use of degradable polymers, especially with starch and aliphatic polyesters.

31. Reference Gelatin Manufacturers Institute of America Members as of January 2012, Gelatin Handbook. Djagny B. K.,Wang Z. , Xu S. ,Gelatin: A Valuable Protein for Food and Pharmaceutical Industries: Review, Critical Reviews in Food Science and Nutrition, 41(6):481–492 (2001 ). Wiley J. & Sons, Encyclopedia of Polymer Science and Technology. Ward , A. G., Structure and Properties of Gelatin , Food, 1951; 20: 255. Ames , W. M., The Conversion of Collagen to Gelatin and their Molecular Structures, J. Sci. Food Agric. ,1952; 3: 454–463. R . T. Jones, in K. Ridgway, ed., Hard Capsules Development and Technology, The Pharmaceutical Press, London, 1987, pp. 41–42. Remington’s Pharmaceutical Science, 1985. 17th edition, Mach Publishing Company. The United States Pharmacopeia XXII (USP XXII–NFXVII), the United States Pharmacopeial Convention, Inc., Rockville, Md., 1989. Dutta P.K., Dutta J., Tripathi V.S., Chitin and Chitosan: Chemistry, properties and applications,Journal of Scientific and Industrial Research, Vol.63,January 2004, pp. 20-31. Bansal V., Sharma S. K., Sharma N.,Pal O.P., Malviya R., Applications of Chitosan and Chitosan derivatives in Drug Delivery,Advances in Biological Research,Vol . 5(1),2011,pp. 28-37 .

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