JBNB  Vol.6 No.1 , January 2015
Synthesis, Characterization, and Study of PLGA Copolymer in Vitro Degradation
ABSTRACT
The poly(lactic-co-glycolic acid), known as PLGA, is one of the main bioreabsorbable polymers used in the field of medicine today. This copolymer is widely applied in sutures, devices geared toward the controlled release of medication, and the guided regeneration of bone tissue as it presents a short degradation time. This work aimed to synthesize the 82/18 PLGA (expressed by the mass ratio of D,L-lactide and glycolide, respectively), to characterize and study the in Vitro degradation in the form of rods in phosphate buffer solution (PBS). The copolymer was synthesized by opening the cyclic dimer rings of the monomers D,L-lactide and glycolide, in the presence of the tin octanoate initiator and of the lauryl alcohol co-initiator. The characterization of the copolymer and the follow-up of its in vitro degradation were studied using: Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Infrared Molecular Absorption Spectroscopy with Fourier Transform (FTIR), Rheometry, and Scanning Electron Microscopy (SEM). Through these characterization techniques, it was possible to obtain the glass transition temperature, thermal stability, chemical composition, morphology, and molar mass of both the synthesized and the degraded copolymer. The molar mass of the synthesized copolymer was, approximately, 106 g·mol-1. The degradation rate of PLGA significantly increased from the 19th to the 28th day in PBS. After 28 days in PBS, the glass transition temperature and the molar mass reduced from 45°C to 17°C and from 1.5 × 106 g·mol-1 to 7.5 × 10g·mol-1, respectively. The pH of the medium has a significant influence on the copolymer degradation profile. When it diminishes, it accelerates the degradation process, resulting in smaller PLGA polymer chains. This pH dependent degradation can be useful for drug release systems.

Cite this paper
Silva, A. , Cardoso, B. , Silva, M. , Freitas, R. and Sousa, R. (2015) Synthesis, Characterization, and Study of PLGA Copolymer in Vitro Degradation. Journal of Biomaterials and Nanobiotechnology, 6, 8-19. doi: 10.4236/jbnb.2015.61002.
References
[1]   Ratner, B.D. and Hoffman, A.S. (1996) Biomaterials Science—An Introduction to Materials in Medicine. Elsevier, New York.

[2]   Langer, R. and Peppas, N.A. (2003) Advances in Biomaterials, Drug Delivery, and Bionanotechnology. Alche Journal, 49, 2990-3006. http://dx.doi.org/10.1002/aic.690491202

[3]   Stevanovic, M., Maksin, T., Petkovic, J, Filipic, M. and Uskokovic, D. (2009) An Innovative, Quick and Convenient Labeling Method for the Investigation of Pharmacological Behavior and the Metabolism of Poly(DL-lactide-coglyco- lide) Nanospheres. Nanotechnology, 20, 1-12.
http://dx.doi.org/10.1088/0957-4484/20/33/335102

[4]   Hoffman, A.S. (2008) The Origins and Evolution of “Controlled” Drug Delivery Systems. Journal of Controlled Release, 132, 153-163. http://dx.doi.org/10.1016/j.jconrel.2008.08.012

[5]   Park, J.H., Lee, S., Kim, J.H., Park, K., Kim, K. and Kwon, I.C. (2008) Polymeric Nanomedicine for Cancer Therapy. Progress in Polymer Science, 33, 113-137.
http://dx.doi.org/10.1016/j.progpolymsci.2007.09.003

[6]   Pamula, E. and Menaszak, E. (2008) In Vitro and in Vivo Degradation of Poly(L-lactide-co-glycolide) Films and Scaffolds. Journal of Materials Science: Materials in Medicine, 19, 2063-2070.
http://dx.doi.org/10.1007/s10856-007-3292-2

[7]   Duarte, M.A.T., Duek, E.A.R. and Motta, A.C. (2014) In Vitro Degradation of Poly (L-co-D,L lactic acid) Containing PCL-T. Polímeros, 24, 1-8. http://dx.doi.org/10.4322/polimeros.2014.056

[8]   Xiaoling, L. and Haskara, R.J. (2006) Design of Controlled Release Drug Delivery Systems. MacGraw-Hill, New York.

[9]   Stevanovic, M. and Skokovic, D. (2009) Poly(lactide-co-glycolide)-Basedmicro and Nanoparticles for the Controlled Drug Delivery of Vitamins. Current Nanoscience, 5, 1-14.

[10]   Stevanovic, M., Radulovic, A., Jordovic, B. and Uskokovic, D. (2008) Poly(DL-lactide-co-glycolide) Nanospheres for the Sustained Release of Folic Acid. Journal of Biomedical Nanotechnology, 4, 349-358.
http://dx.doi.org/10.1166/jbn.2008.021

[11]   Liang, R.C., Li, X., Shi, Y., Wang, A., Sun, K., Liu, W.H. and Li, Y.X. (2013) Effect of Water on Exenatide Acylation in Poly(lactide-co-glycolide) Microspheres. International Journal of Pharmaceutics, 454, 344-353.
http://dx.doi.org/10.1016/j.ijpharm.2013.07.012

[12]   Meng, Z.X., Zheng, W., Li, L. and Zheng, Y.F. (2011) Fabrication, Characterization and in Vitro Drug Release Behavior of Electrospun PLGA/Chitosan Nanofibrous Scaffold. Materials Chemistry and Physics, 125, 606-611.
http://dx.doi.org/10.1016/j.matchemphys.2010.10.010

[13]   Rios, M. (2005) Polymers for Controlled Release: Formulation Follows Function. Pharmaceutical Technology, 29, 42-50.

[14]   Mundargi, R.C., Babu, V.R., Rangaswamy, V., Patel, P. and Aminabhavi, T.M. (2008) Nano/Micro Technologies for Delivering Macromolecular Therapeutics Using Poly(D,L-lactide-co-glycolide) and Its Derivatives. Journal of Controlled Release, 125, 193-209.
http://dx.doi.org/10.1016/j.jconrel.2007.09.013

[15]   Cohen-sela, E., Chorny, M., Koroukhov, N., Danenberg, H.D. and Golomb, G. (2009) A New Double Emulsion Solvent Diffusion Technique for Encapsulating Hydrophilic Molecules in PLGA Nanoparticles. Journal of Controlled Release, 133, 90-95. http://dx.doi.org/10.1016/j.jconrel.2008.09.073

[16]   Bae, S.E., Son, J.S., Park, K. and Han, D.K. (2009) Fabrication of Covered Porous PLGA Microspheres Using Hydrogen Peroxide for Controlled Drug Delivery and Regenerative Medicine. Journal of Controlled Release, 133, 37-43.
http://dx.doi.org/10.1016/j.jconrel.2008.09.006

[17]   Jain, R.A. (2000) The Manufacturing Techniques of Various Drug Loaded Biodegradable Poly(lactídeo-co-glicolídeo) (PLGA) Devices. Biomaterials, 21, 2475-2490. http://dx.doi.org/10.1016/S0142-9612(00)00115-0

[18]   Soares, A.Q., Oliveira, L.F., Rabelo, D. and Souza, A.R. (2005) Polímeros Biodegradáveis: Novas Perspectivas para as Ciências Farmacêuticas. Revista EletrÔnica de Farmácia, 2, 202-205.

[19]   Ji, W., Yang, F., Seyednejad, H., Chen, Z., Hennink, W.E., Anderson, J.M., Beucken, J.J.J.P. and Jansen, J. (2012) Biocompatibility and Degradation Characteristics of PLGA-Based Electrospun Nanofibrous Scaffolds with Nanoapatite Incorporation. Biomaterials, 33, 6604-6614. http://dx.doi.org/10.1016/j.biomaterials.2012.06.018

[20]   Kang, S.W., Yang, H.S., Seo, S.W., Han, D.K. and Kim, B.S. (2008) Apatite-Coated Poly(lactic-coglycolic Acid) Microspheres as an Injectable Scaffold for Bone Tissue Engineering. Journal of Biomedical Materials Research Part A, 85, 747-756. http://dx.doi.org/10.1002/jbm.a.31572

[21]   Qi, F., Wu, J., Yang, T., Ma, G. and Su, Z.G. (2014) Mechanistic Studies for Monodisperse Exenatide-Loaded PLGA Microspheres Prepared by Different Methods Based on SPG Membrane Emulsification. Acta Biomaterialia, 10, 4247- 4256. http://dx.doi.org/10.1016/j.actbio.2014.06.018

[22]   Sun, L., Xie, Z., Zhao, Y., Wei, H.M. and Gu, Z.Z. (2013) Optical Monitoring the Degradation of PLGA Inverse Opal Film. Chinese Chemical Letters, 24, 9-12. http://dx.doi.org/10.1016/j.cclet.2013.01.012

[23]   Khare, V., Kour, S., Alam, N., Dubey, R.D., Saneja, A., Koul, M., Gupta, A.P., Singh, D., Singh, S., Saxena, A.K. and Gupta, P.N. (2014) Synthesis, Characterization and Mechanistic-Insight into the Antiproliferative Potential of PLGA- Gemcitabine Conjugate. International Journal of Pharmaceutics, 470, 51-62.
http://dx.doi.org/10.1016/j.ijpharm.2014.05.005

[24]   Athanasiou, K.A., Niederauer, G.G. and Agrawal, C.M. (1996) Sterilization, Toxicity, Biocompatibility and Clinical Applications of Polylactic Acid/Polyglycolic Acid Copolymers. Biomaterials, 17, 93-102.
http://dx.doi.org/10.1016/0142-9612(96)85754-1

[25]   Lanao, R.P.F., Leeuwenburgh, S.C.G., Wolke, J.G.C. and Jansen, J.A. (2011) Bone Response to Fast-Degrading, Injectable Calcium Phosphate Cements Containing PLGA Microparticles. Biomaterials, 32, 8839-8847.
http://dx.doi.org/10.1016/j.biomaterials.2011.08.005

[26]   Lanao, R.P.F., Leeuwenburgh, S.C.G., Wolke, J.G.C. and Jansen, J.A. (2011) In Vitro Degradation Rate of Apatitic Calcium Phosphate Cement with Incorporated PLGA Microspheres. Acta Biomaterialia, 7, 3459-3468.
http://dx.doi.org/10.1016/j.actbio.2011.05.036

[27]   Li, H. and Chang, J. (2005) pH-Compensation Effect of Bioactive Inorganic Fillers on the Degradation of PLGA. Composites Science and Technology, 65, 2226-2232.
http://dx.doi.org/10.1016/j.compscitech.2005.04.051

[28]   Merkli, A., Tabatabay, C., Gurny, R. and Heller, J. (1998) Biodegradable Polymers for the Controlled Release of Ocular Drug. Progress in Polymer Science, 23, 563-580.
http://dx.doi.org/10.1016/S0079-6700(97)00048-8

[29]   Astete, C.E. and Sabliov, C.M. (2006) Synthesis and Characterization of PLGA Nanoparticles. Journal of Biomaterials Science, Polymer Edition, 17, 247-289.
http://dx.doi.org/10.1163/156856206775997322

[30]   Houchin, M.L. and Topp, E.M. (2008) Chemical Degradation of Peptides and Proteins in PLGA: A Review of Reactions and Mechanisms. Journal of Pharmaceutical Sciences, 97, 2395-2404.
http://dx.doi.org/10.1002/jps.21176

[31]   Tracy, M.A., Ward, K.L., Firouzabadian, L., Wang, Y., Dong, N., Qian, R. and Zhang, Y. (1999) Factors Affecting the Degradation Rate of Poly(lactide-co-glycolide) Microspheres in Vivo and in Vitro. Biomaterials, 20, 1057-1062.
http://dx.doi.org/10.1016/S0142-9612(99)00002-2

[32]   Tsukadaa, Y., Haraa, K., Bandoa, Y., Huangb, C.C., Kousakaa, Y., Kawashimac, Y., Morishitad, R. and Tsujimotoa, H. (2009) Particle Size Control of Poly(DL-lactide-co-glycolide) Nanospheres for Sterile Applications. International Journal of Pharmaceutics, 370, 196-201.
http://dx.doi.org/10.1016/j.ijpharm.2008.11.019

[33]   Xiao, D., Liu, Q., Wang, D., Xie, T., Guo, T., Duan, K. and Weng, J. (2014) Room-Temperature Attachment of PLGA Microspheres to Titanium Surfaces for Implant-Based Drug Release. Applied Surface Science, 309, 112-118.
http://dx.doi.org/10.1016/j.apsusc.2014.04.195

[34]   Erbetta, C.D.C., Alves, R.J., Resende, J.M., Freitas, R.F.S. and Sousa, R.G. (2012) Synthesis and Characterization of Poly(D,L-lactide-co-glycolide) Copolymer. Journal of Biomaterials and Nanobiotechnology, 3, 208-225.
http://dx.doi.org/10.4236/jbnb.2012.32027

[35]   kasperczyk, J. (1996) Microstructural Analysis of Poly(l-lactide)-co-(glycolide) by 1H and13 C n.m.r. Spectroscopy. Polymer, 37, 201-203.

[36]   Maier, D., Eckstein, A., Friedrich, C. and Honerkamp, J. (1998) Evaluation of Models Combining Rheological Data with the Molecular Weight Distribution. Journal of Rheology, 42, 1153-1173. http://dx.doi.org/10.1122/1.550952

[37]   Thimm, W.B., Friedrich, C., Marth, M. and Honerkamp, J. (1999) An Analytical Relationship between Relaxation Time Spectrum and Molecular Weight Distribution. Journal of Rheology, 43, 1663-1672.
http://dx.doi.org/10.1122/1.551066

[38]   Thimm, W.B., Friedrich, C., Marth, M. and Honerkamp, J. (1999) On the Rouse Spectrum and the Determination of the Molecular Weight Distribution from Rheological Data. Journal of Rheology, 44, 429-438.
http://dx.doi.org/10.1122/1.551094

 
 
Top