PLGA: an biodegradable polymer

“PLGA: Biodegradable Polymer”
• Presented By :
Mr. ROHIT GURAV
M. Pharm (1st Sem.)
Roll no. 511
• Guided By:
Prof. V. M. GAMBHIRE
M. Pharm
Department of Pharmaceutics

RohitGurav*
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.
219-11-2016 PLGA: Biodegradable Polymer

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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 Acid
Polyglycolic acid
Chitosan

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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
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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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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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APPLICATIONS
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.
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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
16

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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

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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-NPs
and solution in phosphate-buffered saline containing 1%
polysorbate80 (pH 7.4) at 37°C

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(a) acetylpuerarin and (b) puerarin plasma concentration–time profiles following intravenous
administration of acetylpuerarin solution and AP-PLGA-NPs

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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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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

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 Electrospun Scaffolds
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Polymer Soln
20 kV
5ml Syringe and 24G
blunt needle
stored in vacuum desiccator
for further characterization

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Cell Adhesion and Cell Proliferation
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SEM showing the adhesion of Schwann cells on the surface of the PLGA and PLGA-peptide
PLGA-PeptidePLGA
1 Day 3 Days 7 Days

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 Cell Adhesion
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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.
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Surface Morphology

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Spectroscopic Analysis
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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
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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

RohitGurav*
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.

RohitGurav*
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

RohitGurav*
• 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

RohitGurav*

PLGA: an biodegradable polymer

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