Recent biomedical applications and patents on ... · Review Article Recent biomedical applications...

Singh G, et.al. Int. J. Pharmacol. Pharm. Sci. (2014) 1;2:30-42 30

International Journal of Pharmacology and Pharmaceutical Sciences 2014; Vol: 1, Issue: 2, 30-42

Review Article

Recent biomedical applications and patents on biodegradable polymer-

PLGA

Gurpreet Singh*,Tanurajvir Kaur, Ravinder Kaur, Anudeep Kaur

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, Punjab (India)

*[email protected]

INTRODUCTION

Extensively used polymers in biomedical applications are naturally occurring or synthetic compounds consisting of large molecules

obtained from linking of simple monomers. Potential biomedical applications of these polymers include carrier based drug delivery

systems, tissue engineering scaffold and cell culture supports [1]. Polymer based drug delivery system can control the rate of drug

release, enhance effective drug solubility, minimize drug degradation, contribute to reduced drug toxicity and facilitate control of

drug uptake, which significantly contributes to therapeutic efficiency of a drug [2]. Some desirable characteristics of polymer for

drug delivery system should be [3]:

Natural or synthetic origin, less toxicity and biodegradable in nature

In vivo degradation at a well-defined rate and degraded products readily excreted from the body.

No toxic endogenous impurities or no residual chemicals used in their preparation, e.g. cross linking agents

Examples of naturally derived polymers include starch, chitosan, alginate, collagen and synthetic polymers includes poly

(alkylcyanoacrylates), poly (anhydrides) and polyesters [4]. Amongst them, the thermoplastic aliphatic polyesters, such as polylactic

acid, poly glycolic acid and especially the copolymer poly(lactic-co-glycolic acid) (PLGA) used as biomaterials for biomedical

applications on the basis of available toxicological and clinical data [5]. The family of homo and co-polymers derived from lactic

and glycolic acids monomers have received a considerable attention as excipients since 1973 in pharmaceutical industry due to its

In the area of carrier drug delivery system, various natural and synthetic polymers are used. The natural

polymers have many formulation problems such as instability, irreproducibility, changes in aesthetics

on storage, uncontrollable formulation characteristics. On the other hand, synthetic polymers are either

modified from natural polymers or completely synthesized from synthetic monomers. They possess

properties that seem to solve the problems of natural polymers and more stable than the natural

polymers. In other words, they have mechanical properties that match their application, provide

sufficiently stability during formulation, transportation and use. Synthetic polymers have long shelf

life as compare to natural polymers. Examples of synthetic polymers used in drug delivery systems

are polymethacrylates (Eudragit-E, Eudragits-L, Eudragit-S, Eudragit-RS, Eudragit-RL), Polyacrylic

acid (carbomer), Cellulose ethers (methylcellulose, ethylcellulose, hydroxypropyl methycellulose) and

Polyesters (copolymers of lactic acid, glycolic acid and ε-hydroxycaproic acid). This review presents

the recent applications and patents of poly(lactic-co-glycolic) acid (PLGA) in biomedical applications

with a focus on the understanding of some specific physicochemical characteristics which play an

important role in their characterization.

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International Journal of Pharmacology and

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Article Information Abstract

Keywords:

PLGA Patents

Supplier grades,

NMR

FTIR


attractive properties [6]: (i) biodegradability and biocompatibility, (ii) approval in drug delivery systems for parenteral

administration by FDA and European Medicine Agency (EMA) (iii) well define methods of production for hydrophilic or

hydrophobic small molecules or macromolecules in various carrier based drug delivery system, (iv) drug protection from

degradation, (v) sustained release, (vi) modification of PLGA for better interaction with biological materials (vii) possibility to

target specific organs or cells [7].

Homopolymers and copolymers of aliphatic polyesters have molecular weight ranging from 2000 to >100 000. The polyesters

include poly (e-caprolactone), poly (lactic acid) or poly (lactide) (PLA), and poly (lactic-co-glycolic acid) or poly (lactide-co -

glycolide) (PLGA or PLG, respectively) as classified in Table 1.

Table 1: Classification of polyester polymers [8]

Main chain Number of repeating units Examples of polyesters

Aliphatic Homopolymer Polyglycolide or Polyglycolic acid (PGA),

Polylactic acid (PLA), Polycaprolactone (PCL)

Polyhydroxyalkanoate (PHA), Polyhydroxybutyrate (PHB)

Copolymer Polyethylene adipate (PEA), Polybutylene succinate (PBS),

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)

Semi-aromatic Copolymer Polyethylene terephthalate (PET)

Polybutylene terephthalate (PBT)

Polytrimethylene terephthalate (PTT)

Polyethylene naphthalate (PEN)

Aromatic Copolymer Vectran

Physicochemical profile of PLGA

Physicochemical properties of polymers play an important role in characterizing, analyzing and determining structure property

relationships of polymers. Important physicochemical properties of biodegradable polymers include molecular weight,

hydrophobicity, surface charge, crystallinity, composition of the co-polymer, glass transition temperature [9]. Nevertheless, these

properties can be manipulated to modify as per the application of these polymers for a specific purpose [10-12]. List of important

physicochemical properties of PLGA (Figure 1) are mentioned in Table 2.

Figure 1: Structure of Poly (lactide -co-glycolide)

X and Y denote the number of lactide and glycolide unit respectively

Types of PLGA

In pharmaceutical industry, different grades of PLGA are used according to ratio of lactide and glycolide units. List of major

manufactures with their grades have been summarized in table 3.

PLGA synthesis

Poly (lactic-co-glycolic acid) is a copolymer synthesized by means of random ring-opening copolymerization of two different

monomers, the cyclic dimers (1,4-dioxane-2,5-diones) of glycolic acid and lactic acid and linkage via ester bonds as shown in Figure

2. Due to the asymmetrical ß-carbon of lactic acid, D and L stereoisomers exist, and the resulting polymer can be either, D, L, or

racemic DL. The polymerization is usually carried over a period of 2-6 hr at about 175°C temperature. Most commonly stannous


chloride and stannous octoate are used as catalyst for polymerization [6]. The physicochemical properties of the PLGA depend upon

molar ratio and sequential arrangement of lactide-glycolide units [20,21].

PLGA as biodegradable polymer

Biodegradation of the aliphatic polyesters occurs by bulk erosion [22]. The lactide/glycolide polymer chains are cleaved by

hydrolysis as shown in Figure 3 to the monomeric lactic acid and glycolic acid which gets eliminated from the body by metabolism

and exhaled as carbon dioxide and water through the Krebs cycle [23]. Degradation products of PLGA are generally considered

nontoxic to living organisms such as lactic acid, one of the primary breakdown products, which occurs naturally through metabolic

activity in the human body. The higher the content of glycolide units, the lower is the time required for degradation. An exception

to this rule is the copolymer with 50:50 monomers ratio which exhibits faster degradation as compare to other grades. In addition,

polymers that are end-capped with esters demonstrate longer degradation half-lives [24.25].

Table 2: Physiochemical profile of PLGA [13-15]

Synonyms DL-PLGA (X: Y)

Chemical Formula (C6H8O4)m (C4H4O4)n

CAS name Propanoic acid, 2-hydroxypolymer with hydroxyacetic acid

CAS number [26780-50-7]

MDL number MFCD00131930

Molecular weight 40000-100000

Inherent viscosity (mPas) 0.5-0.8

Glass transition (0C) 45-55

Specific gravity (g/ml) 1.30-1.34

Color White- Light Gold

Storage temperature 2-8°C

Solubility Methylene chloride, tetrahydrofuran,Chloroform, Ethyl acetate

Tensile strength (psi) 6000-8000

Commonly Used Grade (L/D) 50:50, 65:35, 75:25, 85:15

Manufacturer & Trade name Purac (Purasorb®); Birmingham Polymers (Lactel®); Boehringer

Ingelheim (Resomer®); and Alkermes (Medisorb®).

Figure 2: synthesis of PLGA


Table 3: List of major manufactures of PLGA with commonly used grades

Company/ Supplier (Commercial name) Grade L/G ratio Inherent viscosity (dl/g) Ref.

PCAS (Expansorb ®) 10P016 50/50E 0.60-0.70 16

10P017 50/50 0.25-0.40

10P001 50/50 0.40-0.55

10P002 75/25 0.38-0.64

10P019 50/50 0.15-0.25

10P003 75/25 0.70-0.90

10P020 85/15 0.15-0.25

10P023 90/10 0.15-0.25

10P022 50/50 0.50-0.65

10P007 90/10 0.35-0.55

10P024 50/50 0.15-0.25

10P008 85/15 0.55-0.75

10P025 90/10 0.15-0.25

10P009 85/15E 0.55-0.75

10P010 65/35E 0.50-0.65

Aldrich ® Evonik Röhm Pharma GmbH (Resomer ®) RG 502 50/50/ 0.16-0.24 17

RG 502 H 50/50 0.16-0.24

RG 503 50/50 0.32-0.44

RG 503 H 50/50 0.32-0.44

RG 504 50/50 0.45-0.60

RG 504 H 50/50 0.45-0.60

RG 505 50/50 0.61-0.74

RG 653 H 65/35 0.32-0.44

RG 752 H 75/25 0.14-0.22

RG 756 S 75/25 0.71-1.0

Purac Biomaterials (Purasorb®) PDLG 7502 75/25 0.2 18

PDLG 7502A 75/25 0.2

PDLG 7507 75/25 0.7

PDLG 5002 50/50 0.2

PDLG 5002A 50/50 0.2

PDLG 5004 50/50 0.4

PDLG 5004A 50/50 0.4

PDLG 5010 50/50 1.0

Wako Pure Chemical Industries PLGA-7505 75/25 0.082-0.098 19

PLGA-7510 75/25 0.119-0.140

PLGA-7515 75/25 0.152-0.185

PLGA-7520 75/25 0.186-0.230

PLGA-5005 50/50 0.088-0.102

PLGA-5010 50/50 0.122-0.143

PLGA-5015 50/50 0.154-0.186

*. A=Acid terminated, E= End group ester, H-series with free carboxyl termini, Non-H-series with ester termini


Figure 3: Hydrolytic degradation of the poly (lactic-co-glycolic acid) chain

CHARACTERIZATION OF PLGA

Fourier transform infrared spectroscopy (FTIR) of PLGA

Infrared spectroscopy is an essential and crucial characterization technique to elucidate the structure chemical composition and the

bonding arrangement of constituents in a homo-polymer, co-polymer, and polymer composite and polymeric materials. As already

reported, IR spectrum of distinct functional groups of PLGA polymer exhibits molecular vibrations of functional groups as

illustrated in Table 4 and Figure 4. Intense bands observed in the region between 1770 and 1750 cm–1, are attributed to the stretching

vibration of the carbonyl groups present in the two monomers. Medium intensity bands between 1300 and 1150 cm–1 were attributed

to asymmetric and symmetric C-C(=O)-O stretches respectively. The bands in these regions are useful in the characterization of

esters. Bands at 3500 cm–1 and 3450 cm–1 in the FTIR spectra for lactide and glycolide are attributed to streching vibrations of OH

group [26, 27].

Table 4: FTIR peaks of functional groups of PLGA

Functional group Corresponding bands (cm-1)

OH end group 3450-3500

C-H stretches 2885- 3010

C=O stretch 1762.6

C-O stretch 1186-1089

C-H Bends 1450-850

Figure 4: Representation of various streching and bending vibrations of PLGA

35

Nuclear Magnetic Resonance (NMR) Analysis of PLGA

NMR spectroscopy is an effective technique to analyze the ratio of D,L-lactide to glycolide in PLGA copolymers on the basis of

area delimitated by the integral of the D,L-lactide methyl proton and the area delimitated by the integral of the glycolide methylene

proton. Most of the reported studies include characterization of modification of PLGA, degradations studies and their resulting

signals are shown in Table 5 and Figure 5.

Table 5: Peaks of Distinct functional group of PLGA in Proton NMR Spectra [26, 28]

Functional Group Corresponding Peak (ppm)

Lactic acid (CH) 5.2

Glycolic acid (CH2) 4.8

Methyl group (D and L-lactic acid repeat units 1.55

Methyl group attached to the hydroxyl endgroup 1.25

Figure 5: Representation of proton NMR resonances of PLGA

Thermal Properties of PLGA

The glass transition temperature (Tg) is an important tool used to determine physical properties of drug and polymer molecules.

Copolymer composition affects glass transition temperature and crystallinity which have indirect effects on degradation rate of

PLGA. Factors like structural change in molecules; cooling rate and incorporation of additives alter the Tg like as case in of PLGA

foams as shown in Table 6. In which, Tg decrease with decrease in molecular weight and lactide content [29, 30].

Table 6: Tg of different grades of PLGA before and after foaming

Tg (°C) Mid point PLGA 50:50 PLGA 65:35 PLGA 75:25 PLGA 85:15

Before foaming 37.34 42.23 42.55 48.72

After foaming 46.13 47.66 51.65 52.09

Singh G, et.al. Int. J. Pharmacol. Pharm. Sci. (2014) 1;2:30-42

36

Biodegradable polymers are promising materials for biomedical and pharmaceutical applications due to safety, tunable

biodegradability, desirable mechanical properties and extensive investigation in carrier based drug delivery system [1]. Many recent

examples of potential biomedical application of PLGA in the treatment of various diseases and in tissue engineering have been

described in Table 7, resent patents in Table 8 and list of approved marked PLGA products in Table 9. These examples clearly

illustrate the promising use of biodegradable PLGA in future for novel concepts.

Table 7: Recent biomedical applications of PLGA

Formulation (Drug/s) Rational of study Ref.

Nanogels (Taxol) Janus nanogel system formed by mixing a prodrug of Taxol (PEGylated Taxol) and a

copolymer of PLGA-PEG-PLGA. Wei et al; reported enhanced inhibition effect on tumor

growth in a mice breast cancer model. Results suggested that Janus nanogel can potentially

used as delivery system for cancer therapy.

31

Differently charged

PLGA nanoparticles

(Paclitaxel)

Paclitaxel-loaded small PLGA nanoparticles (49 nm and 95 nm in size) with positive or

negative surface charges were prepared without detergent for delivering drug into PC3 cells. It

has been reported that nanoparticle mode of delivery highly improves paclitaxel efficiency by

up to two log-increases.

32

Aptamer conjugated

PLGA nanoparticles

(Paclitaxel)

The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs were synthesized

and specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently

tagged PLGA NPs to the target cancer cells induced by aptamers was observed in two cell lines

L929 and MCF-7 which confirmed that targeted cancer cells were killed while control cells

were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and

uptake to the target cancer cells exhibited increased therapeutic effect of the drug.

33

Porous PLGA

Microparticles

(Doxorubicin)

Inhalable highly porous large PLGA microparticles with incorporated doxorubicin and surface-

attached with TRAIL were fabricated using a w/o/w double emulsification method for the

treatment of lung cancer. The anti-tumor efficacy of pulmonary administered nanoparticles was

improved in animal model.

34

Modified mPEG-PLGA-

PLL nanoparticles

(cisplatin)

Epidermal growth factor (EGF) modified methoxy polyethylene glycol-polylactic-co-glycolic

acid-polylysine encapsulated cisplatin nanoparticles were prepared for solving the toxicity of

cisplatin and improving therapeutic efficiency. Results showed remarkable high cell apoptosis

in vitro and In vivo due to change in drug distribution decrease the nephrotoxicity and improve

significantly therapeutic efficiency without inducing obvious system toxicity.

35

Conjugated PLGA

nanoparticles

(Tetraiodothyroacetic

acid)

Bharali et al; evaluated tetraiodothyroacetic acid (tetrac) conjugated to poly(lactic-co-glycolic

acid) nanoparticles both in vitro and in vivo for the treatment of drug-resistant breast cancer.

Drug loaded NPs enhanced inhibition of tumor-cell proliferation at a low-dose equivalent of

free tetrac. In vivo treatment with either tetrac or T-PLGA-NPs resulted in a three- to five-fold

inhibition of tumor weight.

36

PLGA nanoparticle

entrapped killed porcine

reproductive and

respiratory syndrome

virus vaccine (PRRSV)

Biodegradable PLGA nanoparticle-entrapped killed PRRSV vaccine (Nano-KAg)

administered intranasally to pigs and evaluated the immune response. Nano-KAg vaccine

elicits better anti-PRRSV immune response which required to better clear viremia in pigs.

37

Biomedical Applications of PLGA



DNA vaccine loaded

PLGA microspheres

(ompA-hly)

PLGA was used as a carrier for a divalent fusion DNA vaccine encoding the Aeromonas veronii

outer membrane protein A (ompA) and Aeromonas hydrophila hemolysins (hly) protein.

Loading of ompA-hly antigen module on PLGA microspheres were accomplished by water-

in-oil-in-water (W/O/W) encapsulation. Mice received ompA-hly antigen-loaded PLGA

microspheres by intraperitoneal or intragastric administration mounted strong and sustained

IgG response, which was significantly higher than those achieved by pET-28a-ompA-hly

antigen alone. OmpA-hly antigen-loaded PLGA microsphere vaccine uniquely conferred a

long lasting sterile immunity against challenge infection.

38

PLGA-encapsulated

vaccine for Uronema

marinum.

Harikrishna et al; investigates the efficacy of PLGA-encapsulated vaccine on innate and

adaptive immune response in Epinephelus bruneus against Uronema marinum. The serum

lysozyme activity, antiprotease activity, and antibody level were significantly enhanced in fish

immunized with vaccine and PLGA-encapsulated vaccine on weeks 2 and 4. The cumulative

mortality was low in PLGA-encapsulated vaccine.

39

Surface modified PLGA

nanoparticles for nasal

vaccine delivery

Study includes preparation of Hepatitis B surface Antigen (HBsAg) encapsulated PLGA,

chitosan coated PLGA (C-PLGA), and Glycol chitosan coated PLGA (GC-PLGA)

nanoparticles (NPs). Results revealed that PLGA NPs exhibit negative surface charge, whereas

C-PLGA and GC-PLGA NPs exhibited positive surface charge. The GC-PLGA NPs

demonstrated lower clearance and better local and systemic uptake compared to chitosan

coated and uncoated PLGA NPs. In vivo immunogenicity studies indicated that GC-PLGA NPs

could induce significantly higher systemic and mucosal immune response compared to PLGA

NPs and C-PLGA NPs.

40

PLGA and

PLGA/gelatin

nanofibers

Surface mineralization is an effective method to produce calcium phosphate apatite coating on

the surface of bone tissue scaffold which could create an osteophilic environment similar to the

natural extracellular matrix for bone cells. study include preparation of mineralized PLGA and

PLGA/gelatin electrospun nanofibers via depositing calcium phosphate apatite coating on the

surface of these nanofibers to fabricate bone tissue engineering scaffolds by concentrated

simulated body fluid method, supersaturated calcification solution method and alternate

soaking method. Result revealed that a larger amount of calcium phosphate was deposited on

the surface of PLGA/gelatin nanofibers rather than PLGA nanofibers because gelatin acted as

nucleation center for the formation of calcium phosphate.

41

Transferrin-conjugated

magnetic silica PLGA

nanoparticles

(Doxorubicin and

Paclitaxel)

Transferrin-conjugated magnetic silica PLGA nanoparticles (MNP-MSN-PLGA-Tf NPs) were

formulated to overcome poor transport across blood brain barriers. Doxorubicin (DOX) and

paclitaxel (PTX), loaded NPs were evaluated for their anti-proliferative effect. Results showed

that cells treated with DOX-PTX-NPs-Tf with magnetic field showed the highest cytotoxicity

as compared to those treated with DOX-PTX-NPs-Tf, DOX-PTX-NPs, DOX-PTX-NPs-Tf

with free Tf. In particular, the DOX-PTX-NPs-Tf treatment exhibited the strongest anti-glioma

activity as compared to the PTX-NPs-Tf, DOX-NPs-Tf or DOX-PTX-NPs treatment.

42

Multiple agents loaded

PLGA nanoparticles

(salvianolic acid B (Sal

B), tanshinone IIA (TS

Multiple agents loaded PLGA nanoparticles of salvianolic acid B (Sal B), tanshinone IIA (TS

IIA) and panax notoginsenoside (PNS) were prepared by double emulsion/solvent evaporation

method. Optimized NPs administration intratympanic in guinea pigs greatly improved drug

distribution within the inner ear, cerebrospinal fluid (CSF) and brain tissues compared with

intravenous administration. These findings suggest that PLGA NPs-based delivery system via

43

38

IIA) and panax

notoginsenoside )

inner ear administration was a promising candidate to brain delivery for the treatment of brain

diseases.

PLGA microspheres

(lornoxicam)

Investigate the joint tissue distribution and pharmacodynamics of Lornoxicam (Lnxc)

following intra-articular injection of either Lnxc suspensions or sustained release Lnxc-loaded

PLGA microspheres (Lnxc-MS), as well as the biocompatibility of PLGA microspheres with

or without drugs. The plasma drug concentration decreased in rats and retention time increased

in rats' joint with intra-articular injections of microspheres, revealing good targeting efficiency

and decreased systemic toxicity. intraarticular Lnxc-MS have considerable potential for

creating a sustained release Lnxc for Osteoarthritis.

44

PLGA Nanosuspensions

for Ophthalmic

Application

(Moxifloxacin)

Investigation was to prepare a colloidal ophthalmic formulation to improve the residence time

of moxifloxacin. Moxifloxacin-loaded PLGA nanosuspensions were prepared by using the

solvent evaporation technique. The optimised nano-suspension was found to be more active

against S. aureus and P. aeruginosa as compared to the marketed eye drops.

45

Antibacterial drug-

loaded PLGA

nanoparticles

(Cefixime)

Cefixime loaded PLGA nanoparticles using modified precipitation method. Optimized

formulation has significant antibacterial activity against intracellular multidrug resistance

(MDR) of Salmonella typhi.

46

Table 8: List of recent patents on PLGA in biomedical applications

Patent Number Inventor Name Publication

Date

Abstract Ref.

US20120202064A1 Ho, Mei-Ling; Chang, Je-

Ken; Eswaramoorthy,

Rajalakshmanan; Wu,

Shun-Cheng.

2012/08/09 A short term controlled release of poly(lactic-co-

glycolic acid) cross linked alendronate (PLGA-ALN)

is provided. The PLGA-ALN is constructed into 3D

scaffolds (PLGA-ALN-3D).

47

WO2012101639 Benita, Simon; Nasser,

Taher; Karra, Nour;

Badihi, Amit.

2012/12/13 Invention relates to a poly (lactic glycolic) acid

(PLGA) nanoparticle associated with therapeutic

agents for a variety of therapeutic applications. Solid

nanoparticles contain PLGA, octanoic acid, DHEA,

Tween-80, acetone, Solutol HS15 and water.

48

CN102552984 Zhang, Peibiao; Wu,

Xiaodong; Chen, Xuesi;

Cui, Liguo; Wang,

Zongliang; Wang, Yu;

Wu, Haitao.

2012/07/11 The manufacturing method of tissue engineering

scaffolding comprises the steps of: mixing

poly(lactic-co-glycolic acid) soln., dimethyl sulfone

soln. and hydroxyapatite suspension to obtain a mixed

suspension, and freeze-drying.

49

US20110305766 Ho, Mei-Ling; Wang,

Gwo-Jaw; Chang, Je-Ken;

Fu, Yin-Chih; Tzeng,

Cherng-Chyi;

Eswaramoorthy,

Rajalakshmanan.

2011/12/15 Invention provides a method for producing a

controlled release microsphere with mean av. size

greater than 50 μm, by water-in-oil (w/o) emulsion

comprising an inner aq. layer contain a

pharmaceutically effective amount of a biological

active polypeptide with activity similar to parathyroid

50


39

hormone, (PVA) soln. to form a water-in-oil-in-water

(w/o/w) double emulsion and then desorbing the

solvent in the oil layer.

CN101940553 He, Yanjin; Chang, Jin;

Lin, Tingting; Luo, Hao;

Zhu, Limin; Liang,

Xiaofei; Chen, Luxia.

2011/01/12 The process for preparing the folic acid-vincristine

targeting sustained-release nanosphere is used in

prepn. of drugs for targeting treatment of orbital

adenoid cystic carcinoma with the advantages of high

partial drug concentration, long action time and little

untoward effect.

51

CN101940782 Li, Shiqiao; Wang,

Honghu.

2011/01/12 Long-acting microspheres of lanreotide for injection

have advantages of good compliance, low cost and

simple manufacturing process.

52

Table 9: List of approved marketed product of PLGA based drugs [53-55]

Drug Trade name ® Uses Duration

Weeks

Company

#Leuprolide acetate Lupron Depot Prostate cancer 12 -16 TAP Pharmaceuticals

*Leuprolide acetate Eligard Prostate cancer 12 -24 Sanofi Aventis

*Goserelin acetate Zoladex Prostate cancer 4 or 12 AstraZeneca

*Buserelin acetate Suprefact Depot Prostate cancer 8 or 12 Sanofi Aventis

#Triptorelin pamoate Decapeptyl Prostate cancer 4 Ferring Pharmaceuticals

#Octreotide acetate Sandostatin LAR Acromegaly 4 Novartis

#Lanreotide Somatuline LA Acromegaly 2 Ipsen

#Triptorelin pamoate Trelstar Depot Prostate cancer 4 Watson Pharma, Inc.

#Triptorelin pamoate Trelstar LA Prostate cancer 12 Watson Pharma, Inc.

#Risperidone Risperdal Consta Antipsychotic 2 Janssen Pharmaceuticals

#Naltrexone Vivitrol Alcohol dependence 4 Alkermes, Inc.

*Somatropin Nutropin Depot Growth deficiencies 4 or 12 Genentech, Inc

**Carmustine Gliadel Malignant glioma 80 Arbor Pharmaceuticals,

**Minocycline HCl Arestin Periodontitis. 2 OraPharma

*Eprinomectin Longrange Parasitic diseases 10-16 Merial Limited,

Gluteal IM #, Abdominal SC *, Implants **

CONCLUSIONS

Biodegradable polymers have proved their potential for the development of new, advanced and efficient drug delivery system.

PLGA is approved by the FDA and EMA in various drug delivery systems. Therefore, in coming years, there is going to be continued

interest in PLGA biodegradable polymer for biomedical applications which include tissue engineering, vascular engineering, nerve

regeneration, cartilage tissue engineering, bone tissue engineering. The main reason which attributes in frequent use and the success

of using PLGA polymer are its safety, biodegradability and biocompatibility.


40

Conflict of interest

No conflict to disclose

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