PLGA: an biodegradable polymer

Poly(lactic-co-glycolic--acid); widely used biodegradable polymer.

1. STES’s Sinhgad College of Pharmacy, Vadgaon Bk, Pune “PLGA: Biodegradable Polymer” Seminar on: Presented By : Mr . ROHIT GURAV M. Pharm ( 1 st Sem.) Roll no. 511 Guided By: Prof. V. M. GAMBHIRE M. Pharm Department of Pharmaceutics

2. Introduction Polymer is derivation of ancient Greek word ‘ Polus ’ which means many, much and ‘ Meros ’ means parts The term was coined in 1833 by Jons Jacob Berzelius. 2 17/11/2016 PLGA: Biodegradable Polymer

3. Biodegradable Polymer They are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways. Example:- Polylactic Acid Polyglycolic acid Chitosan 3 Poly(lactic-co-glycolic acid) 17/11/2016 PLGA: Biodegradable Polymer

4. 4 Poly(lactic-co-glycolic-acid) ) PLGA is a synthetic polymer made from monomers of lactide and glycolide . 1960: PGA was used in the first totally biodegradable Sutures developed . 1970: marketed under the name Dexon . 1970:PLGA (10:90) Sutures, were marketed as Vicryl . 17/11/2016 PLGA: Biodegradable Polymer

5. Solubility :- (High Lactic acid) Soluble in organic solvent such as C hloroform and Dichloromethane , E thyl acetate, A cetone . (High Glycolic acid) It is insoluble in most organic solvents. Soluble in Highly fluorinated solvents, such as hexafluoroisopropanol . Glass Transition Temp . ( Tg ) : 44-55 C 5 Properties 17/11/2016 PLGA: Biodegradable Polymer

6. 6 tin (II) 2-ethylhexanote , tin (II) alkoxides Two different monomers, Glycolic acid Lactic acid Catalyst.: tin (II) 2-ethylhexanote, tin (II) alkoxides aluminium isoproxide E ster linkages gives the formation of PLGA. Synthesis 17/11/2016 PLGA: Biodegradable Polymer *Fang Wang, 2016, Synthesis and characterization of poly(lactic acid-co-glycolic acid) complex microspheres as drug carriers, Journal of Biomaterials Applications ,1–9

7. 7 85% aqueous solution of lactic acid and glycolic acid were put into a 100mL three-necked flask The reaction system was hydrated at the constant temperature of 150 C Viscous oligomers were formed a mechanical stirrer and a reflux condenser packed then 13,300 Pa for 2 h, and 1300 Pa for 4 h. atmospheric pressure for 2 h, TiCl2 and TSA (1:1) were added into the reaction system . pressure 100Pa , 180 C with mechanical stirring for 12 h Product dissolved in chloroform and subsequently precipitated into diethyl ether filtered and dried under vacuum at 65 C PLGA 17/11/2016 PLGA: Biodegradable Polymer Process

8. 8 The PLGA co-polymer undergoes Hydrolytic degradation through cleavage of its backbone ester linkages The degradation products are easily metabolized in the body via the Krebs cycle and are eliminated Biodegradation 17/11/2016 PLGA: Biodegradable Polymer

9. 9 Factor affecting Degradation Composition Crystallinity pH Size and Shape Molecular weight 17/11/2016 PLGA: Biodegradable Polymer Shweta Sharma, et. al, 2015 , PLGA-based nanoparticles: a new paradigm in biomedical applications, Trends in Analytical Chemistry, 32, pp 176-184

10. 10 Fig. 3: release profiles for 50:50, 65:35, 75:25 and 85:15 poly lactic-co-glycolic acid. Effect of composition on Shelf life poly lactic-co-glycolic acid. * Gadad A.P. et.al, 2012, “Study of Different Properties and Applications of Poly Lactic- coglycolicAcid (PLGA) Nanotechnology: An Overview”, Indian Drugs , 49(12), pp. 5-22. 17/11/2016 PLGA: Biodegradable Polymer

11. Cardiovascular disease Diagnosis 11 Immunology & Vaccines Cancer Devices APPLICATIONS Tissue engineering 17/11/2016 PLGA: Biodegradable Polymer Shweta Sharma, et. al, 2015 , PLGA-based nanoparticles: a new paradigm in biomedical applications, Trends in Analytical Chemistry, 32, pp 176-184

12. Modification of PLGA Polyethylene glycol Polysorbate Vitamin E TPGS 12 17/11/2016 PLGA: Biodegradable Polymer

13. PEG is a non ionic, hydrophilic polymer. PEGylation prevent the interaction of the nanoparticles with the macromolecules present in the body . PEGylation enhances the aqueous solubility and stability. 13 1. Polyethylene glycol *Tania B., 2008,PEGylation strategies for active targeting of PLA/PLGA nanoparticles, Journal of Biomedical Materials Research Part A, pp 263-277 17/11/2016 PLGA: Biodegradable Polymer

14. 14 Conjugation of PEG to the surface of premade PLGA NPs. *Tania B., 2008,PEGylation strategies for active targeting of PLA/PLGA nanoparticles, Journal of Biomedical Materials Research Part A, pp 263-277 17/11/2016 PLGA: Biodegradable Polymer

15. 2. Polysorbate It is non ionic surfactant and emulsifier often used in foods and cosmetics. It enhance ability to cross the Blood Brain Barrier. 15 *Tania B., 2008,PEGylation strategies for active targeting of PLA/PLGA nanoparticles, Journal of Biomedical Materials Research Part A, pp 263-277 17/11/2016 PLGA: Biodegradable Polymer

16. 3. Vitamin E TPGS It is a synthetic water soluble form of Vitamin E. TPGS is a polyethylene glycol derivative of α- tocopherol that enables water solubility . The molecule has shown to improve the nanoparticle adhesion to the cells 16 *Tania B., 2008,PEGylation strategies for active targeting of PLA/PLGA nanoparticles, Journal of Biomedical Materials Research Part A, pp 263-277 17/11/2016 PLGA: Biodegradable Polymer

17. Crosslinking Radiation has been used as a processing technique to modify the properties of polymers C hain scission Crosslinking. Crosslinking. Poly-functional monomers (PFM), such as triallylisocyanurate (TAIC) can be used to cross-link PLGA. 17 17/11/2016 PLGA: Biodegradable Polymer *Lester Phong et. al, 2010, Properties and hydrolysis of PLGA and PLLA cross-linked with electron beam radiation, Polymer Degradation and Stability 95 (2010), pp 771-777

18. 18 Water uptake of cross-linked (CL - black symbols) and non-cross-linked (non-CL - white symbols) PLGA and PLLA films with degradation time. Mass loss of cross-linked (CL - black symbols) and non-cross-linked (non-CL - white symbols) PLGA and PLLA films with degradation time. *Lester Phong et. al, 2010, Properties and hydrolysis of PLGA and PLLA cross-linked with electron beam radiation, Polymer Degradation and Stability 95 (2010), pp 771-777 17/11/2016 PLGA: Biodegradable Polymer Effect of Crosslinking on Degradation

19. 19 Case Study 17/11/2016 PLGA: Biodegradable Polymer

20. Materials Puerarin (NIFDC, Beijing, China). Acetylpuerarin ( Shandong Academy Jinan,China ) PLGA 50:50, (JDB Co., Ltd. (Jinan, China). Polysorbate 80 (SCR Co ., Ltd. ,Shanghai , China). 20 17/11/2016 PLGA: Biodegradable Polymer

21. 21 Method 17/11/2016 PLGA: Biodegradable Polymer

22. 22 In-vitro release profiles of acetylpuerarin from PLGA-NPs and solution in phosphate-buffered saline containing 1% polysorbate80 (pH 7.4) at 37°C 17/11/2016 PLGA: Biodegradable Polymer In-Vitro Release of Acetylpuerarin

23. 23 (a) acetylpuerarin and (b) puerarin plasma concentration–time profiles following intravenous administration of acetylpuerarin solution and AP-PLGA-NPs 17/11/2016 PLGA: Biodegradable Polymer PDC of Acetylpuerarin ( i . v.)

24. 24 The concentrations of (a) acetylpuerarin and (b) puerarin in the brain in mice at different times following intravenous administration of acetylpuerarin solution and AP-PLGA-NPs 17/11/2016 PLGA: Biodegradable Polymer Acetylpuerarin Conc n in Brain

25. Conclusion :Case Study P olysorbate 80-coated AP-PLGA-NPs. PLGA-NPs significantly enhanced the distributions of Drug in Brain It can be concluded that Polysorbate 80-coated PLGA-NPs can improve the permeability of AP cross the BBB. 25 17/11/2016 PLGA: Biodegradable Polymer

26. Recent Application 26 17/11/2016 PLGA: Biodegradable Polymer

27. Materials PLGA ( Lakeshore Biomaterials, Birmingham, USA .) DCM and DMF (Merck, India) TFE (Sigma-Aldrich , Bangalore, India) RADA 16-I-BMHP1 ( Bioconcept Labs Pvt Ltd, Gurgaon) Rat Schwan Cells (ATCC, Virginia, USA) PBS Solution pH 7.4 ( Gibco , Grand Island, NewYork , USA) 27 17/11/2016 PLGA: Biodegradable Polymer

28. Method Fabrication of PLGA and PLGA-Peptide electrospun scaffolds 28 17/11/2016 PLGA: Biodegradable Polymer

29. Electrospun Scaffolds 29 Polymer Sol n 20 kV 5ml Syringe and 24G blunt needle 0.001 mL/min fibers were collected stored in vacuum desiccator for further characterization 17/11/2016 PLGA: Biodegradable Polymer

30. Cell Adhesion and Cell Proliferation 30 SEM showing the adhesion of Schwann cells on the surface of the PLGA and PLGA-peptide PLGA-Peptide PLGA 1 Day 3 Days 7 Days 17/11/2016 PLGA: Biodegradable Polymer

31. Cell Adhesion 31 DMEM supplemented with 10% FBS and 1% P/S and maintained at 37˚C in 5% carbon dioxide. Rat Schwann cells sterilized under UV light for 1 hour washed with PBS solution 17/11/2016 PLGA: Biodegradable Polymer

32. Scanning electron micrographs of (A) PLGA and (B1) PLGA-peptide blended nanofibers (B2) Higher magnification of B1 (50,000 X). Arrows indicating self-assembled peptide nanostructures on top of PLGA nanofibers. 32 Surface Morphology 17/11/2016 PLGA: Biodegradable Polymer

33. Spectroscopic Analysis 33 EDX spectra confirming (A) absence of nitrogen peak in PLGA indicating the absence of peptide; (B) presence of nitrogen peak in the PLGA-peptide indicating the presence of peptide; 17/11/2016 PLGA: Biodegradable Polymer

34. Immunocytochemistry 34 Rhodamine-phalloidin staining for the Schwann cells showing actin cytoskeletal morphology on the PLGA and PLGA-peptide samples after 3 days of culture Anti S-100 staining for the Schwann cell phenotype on the (A) PLGA and (B)PLGA peptide blended samples after 3 days of culture. Nucleus Actin Merged 17/11/2016 PLGA: Biodegradable Polymer

35. Conclusion Novel hybrid scaffolds made up of PLGA and the self-assembling peptide, RADA16-IBMHP1 were successfully fabricated by electrospinning. Schwann cell extension and spreading was significantly improved in the peptide blended scaffolds when compared to the PLGA scaffolds . Our results indicate that the designed composite of PLGA+RADA16-I-BMHP1 blended nanofibrous scaffold would pave way for successful and functionary recovery in peripheral nerve tissue engineering applications 35 17/11/2016 PLGA: Biodegradable Polymer

36. Conclusion PLGA polymers have been shown to be excellent delivery carriers for controlled administration of drugs, peptides and proteins due to their biocompatibility and biodegradability. These polymers are increasingly becoming feasible candidates for drug delivery systems, anticancer agents and vaccine immunotherapy . Modified PLGA helps to enhanced the permeability of Drugs. 36 17/11/2016 PLGA: Biodegradable Polymer

37. References Gadad A.P. et.al, 2012, “Study of Different Properties and Applications of Poly Lactic- coglycolicAcid (PLGA) Nanotechnology: An Overview”, Indian Drugs , 49(12), pp. 5-22. Kumar A et.al, “Biodegradable Polymers and Its Applications” International Journal of Bioscience , 2011, vol.1, no.3, pp. 173-176. Leja K and Lewandowicz G., 2010, “Polymer Biodegradation and Biodegradable Polymers – a Review”, Polish J. of Environ. Stud., vol. 19, no.2, pp. 255-266. Nune M et. Al, 2016, “PLGA nanofibers blended with designer self-assembling peptides for peripheral neural regeneration” Materials Science and Engineering C , 62, pp. 329–337. 37 17/11/2016 PLGA: Biodegradable Polymer

38. Yanbin Suna,et.al , 2014, Enhanced antitumor efficacy of vitamin E TPGS-emulsified PLGA nanoparticles for delivery of paclitaxel Colloids and Surfaces B: Biointerfaces 123 716–723 Deqing Suna et. al, 2015, Polysorbate 80-coated PLGA nanoparticles improve the permeability of acetylpuerarin and enhance its brain-protective effects in rats, Journal of Pharmacy And Pharmacology, 67, pp. 1650–1662 Fang Wang, 2016, Synthesis and characterization of poly(lactic acid-co-glycolic acid) complex microspheres as drug carriers, Journal of Biomaterials Applications ,1–9 Lester Phong et. al, 2010, Properties and hydrolysis of PLGA and PLLA cross-linked with electron beam radiation, Polymer Degradation and Stability 95 , pp 771-777 Tania Betancourt, 2008,PEGylation strategies for active targeting of PLA/PLGA nanoparticles, Journal of Biomedical Materials Research Part A, pp 263-277 38 17/11/2016 PLGA: Biodegradable Polymer

39. Shweta Sharma, et. al, 2015 , PLGA-based nanoparticles: a new paradigm in biomedical applications, Trends in Analytical Chemistry, 32, pp 176-184 Zhang K, et. al, 2014, “PEG–PLGA copolymers: Their structure and structure-influenced drug delivery applications”, Journal of Controlled Release, vol. 183, pp. 77–86 Zhiqiang L., 2016, A novel and simple preparative method for uniform-sized PLGA microspheres: Preliminary application in antitubercular drug delivery, Colloids and Surfaces B: Biointerfaces 145, pp 679–687 39 17/11/2016 PLGA: Biodegradable Polymer

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