STES’s Sinhgad College of Pharmacy, Vadgaon Bk, Pune
“PLGA: Biodegradable Polymer”
Seminar on:
• Presented By : Mr. ROHIT GURAV M. Pharm (1st Sem.) Roll no. 511
• Guided By: Prof. V. M. GAMBHIRE
M. PharmDepartment of Pharmaceutics
02/05/2023 PLGA: Biodegradable Polymer
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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.
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Biodegradable Polymer
They are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways.
Example:-Polylactic AcidPolyglycolic acidChitosan
Poly(lactic-co-glycolic acid)
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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.
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• Solubility:- (High Lactic acid) Soluble in organic solvent such as Chloroform and
Dichloromethane, Ethyl acetate, Acetone.(High Glycolic acid)
It is insoluble in most organic solvents. Soluble in Highly fluorinated solvents, such as
hexafluoroisopropanol.• Glass Transition Temp. (Tg) : 44-550 C
Properties
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tin (II) 2-ethylhexanote, tin (II) alkoxides
Two different monomers, Glycolic acid Lactic acid
• Catalyst.: a. tin (II) 2-ethylhexanote, b. tin (II) alkoxides c. aluminium isoproxide
• Ester linkages gives the formation of PLGA.
Synthesis
*Fang Wang, 2016, Synthesis and characterization of poly(lactic acid-co-glycolic acid) complex microspheres as drug carriers, Journal of Biomaterials Applications,1–9
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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 1500C
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, 1800C with mechanical stirring for 12 h
Product dissolved in chloroform and subsequently precipitated into diethyl ether
filtered and dried under vacuum at 650C
PLGA
• Process
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• 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
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Factor affecting
Degradation
Compo
sition
Crysta
llinit
y
pH
Size
and
Shap
e
Mole
cular
weight
Shweta Sharma, et. al, 2015, PLGA-based nanoparticles: a new paradigm in biomedical applications, Trends in Analytical Chemistry, 32, pp 176-184
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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.
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Cardiovascular disease
Diagnosis
Immunology & Vaccines
Cancer
Devices
APPLICATIONS
Tissue engineering
Shweta Sharma, et. al, 2015, PLGA-based nanoparticles: a new paradigm in biomedical applications, Trends in Analytical Chemistry, 32, pp 176-184
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Modification of PLGA
I. Polyethylene glycol
II. Polysorbate
III. Vitamin E TPGS
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• 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.
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
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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
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2. Polysorbate
• It is non ionic surfactant and emulsifier often used in foods and cosmetics. • It enhance ability to cross the
Blood Brain Barrier.
*Tania B., 2008,PEGylation strategies for active targeting of PLA/PLGA nanoparticles, Journal of Biomedical Materials Research Part A, pp 263-277
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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
*Tania B., 2008,PEGylation strategies for active targeting of PLA/PLGA nanoparticles, Journal of Biomedical Materials Research Part A, pp 263-277
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Crosslinking• Radiation has been used as a processing technique
to modify the properties of polymers 1. Chain scission 2. Crosslinking.
Crosslinking.• Poly-functional monomers (PFM), such as
triallylisocyanurate (TAIC) can be used to cross-link PLGA.
*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
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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
Effect of Crosslinking on Degradation
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Case Study
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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).
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Method
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* In-vitro release profiles of acetylpuerarin from PLGA-NPsand solution in phosphate-buffered saline containing 1% polysorbate80 (pH 7.4) at 37°C
In-Vitro Release of Acetylpuerarin
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* (a) acetylpuerarin and (b) puerarin plasma concentration–time profiles following intravenous administration of acetylpuerarin solution and AP-PLGA-NPs
PDC of Acetylpuerarin (i. v.)
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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
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Acetylpuerarin Concn in Brain
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Conclusion :Case Study
• Polysorbate 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.
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Recent Application
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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)
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Method
• Fabrication of PLGA and PLGA-Peptide electrospun scaffolds
PLGA + DCM DMF (8:2), 12%
(w/v)
Peptide + DCM DMF (8:2), 0.1%
(w/v)
PLGA-P
eptid
e
mixtur
e
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Electrospun Scaffolds
Polymer Soln
20 kV
5ml Syringe and 24G blunt needle
0.001 mL/min
fibers were collected
stored in vacuum desiccator for further characterization
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Cell Adhesion and Cell Proliferation
SEM showing the adhesion of Schwann cells on the surface of the PLGA and PLGA-peptide
PLG
A-P
eptid
e
PL
GA
1 Day 3 Days 7 Days
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Cell Adhesion
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
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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.
Surface Morphology
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Spectroscopic Analysis
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;
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Immunocytochemistry
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
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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
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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.
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* 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.
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• 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
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• 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
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