plga: an biodegradable polymer

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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02/05/2023 PLGA: Biodegradable Polymer 3

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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.



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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.



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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



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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.)

PLGA: Biodegradable Polymer 24

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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

02/05/2023

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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plga: an biodegradable polymer

Health & Medicine