Synthesis and Characterization of Poly(lactic-co-glycolic acid) Derived with LGlutamic Acid and L-Aspartic Acid

Öz

Poli(laktik-ko-glikolik asit) sağlık alanında en çok kullanılan, biyouyumlu, biyobozunur özellikte FDA ve EMA onaylı bir polimerdir. Bu çalışmada öncelikle polikondenzasyon ve halka açılma polimerizasyonu ile laktid ve glikolidden PLGA sentezlenmiştir. Daha sonra PLGA ve amino asitlerin 1-etil-3-(3-dimetilaminopropil)karbodiimid (EDC) varlığında reaksiyonu ile PLGA'nın amino asit türevleri sentezlenmiştir. Sentezlenen polimerler PLGA, PLGA-L-glutamik asit (PLGA-G) ve PLGA-L-aspartik asit (PLGA-A)'dir. Bu polimerlerin kimyasal yapısı 1H ve 13C Nükleer Manyetik Rezonans (1H NMR ve 13C NMR), Fourier Dönüşümlü Kızılötesi Spektroskopisi (FTIR), Diferansiyel Taramalı Kalorimetri (DSC) ve Jel Geçirgenlik Kromatografisi (GPC) ile doğrulandı. PLGA-amino asit türevlerinin 13C NMR analizleri incelendiğinde 170 ppm yakınlarında karbonil karbonlarının sayısında artış gözlenerek yapı doğruluğu desteklenmiştir. Ayrıca yine PLGA-amino asit türevlerinin FTIR analizleri incelendiğinde amid bağı karbonil titreşimine ait sinyal 1700 cm-1'de gözlenerek yapı doğrulanmıştır. PLGA-aminoasit türev yapılarının DSC analizi ile tipik endotermik termogram gözlenirken, GPC analizleri ile yapıların düşük molekül ağırlıklı polimerler [~5000-6000 Da] olduğu gösterilmiştir.

Anahtar Kelimeler

• PLGA
• amino asit
• biyobozunur polimer

Proje Numarası

[TSA-2021-7769]

Synthesis and Characterization of Poly(lactic-co-glycolic acid) Derived with LGlutamic Acid and L-Aspartic Acid

Öz

Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible, biodegradable polymer approved by the FDA and EMA, which is the most widely used in the field of health. In this study, PLGA was synthesized primarily from lactide and glycolide by polycondensation and ring-opening polymerization. Then, amino acid derivatives of PLGA were synthesized by the reaction of PLGA and amino acids in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The polymers synthesized were PLGA, PLGA-L-glutamic acid (PLGA-G), and PLGA-L-aspartic acid (PLGA-A). The chemical structure of these polymers was confirmed by 1H and 13C Nuclear Magnetic Resonance (1H NMR and 13C NMR), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Gel Permeation Chromatography (GPC). When the 13C NMR analyses of PLGA-amino acid derivatives were observed, an increase in the number of carbonyl carbons around 170 ppm was found and the structure accuracy was supported. In addition, when the FTIR analyses of PLGA-amino acid derivatives were examined, the structure was confirmed by observing the signal of the amide bond carbonyl vibration at 1700 cm-1. While the typical endothermic thermogram of the PLGA-amino acid derivative structures was observed by DSC analysis, it was shown that the structures were low molecular weight polymers [~5000-6000 Da] by GPC analysis.

Anahtar Kelimeler

• PLGA
• amino acid
• biodegradable polymer

Destekleyen Kurum

Erzincan Binali Yıldırım University Scientific Research Projects Coordination Unit

Proje Numarası

[TSA-2021-7769]

Teşekkür

This research was supported by Erzincan Binali Yıldırım University Scientific Research Projects Coordination Unit with Grant Number [TSA-2021-7769]

Kaynakça

1. [1] Wang, H., Zhang, Y., Liu, Y., Ren, Y., Wang, J, Niu, B., Li, W., (2022) Preparation of curcumin loaded hyaluronic acid-poly (lactic-co-glycolic acid) micelles with pH response and tumor targeting, European Polymer Journal, 177, 111450, https://doi.org/10.1016/j.eurpolymj.2022.111450.
2. [2] Aksoy, E. A., Taskor, G., Gultekinoglu, M., Kara, F., Ulubayram, K., (2018) Synthesis of biodegradable polyurethanes chain-extended with (2S)-bis(2-hydroxypropyl) 2-aminopentane dioate, Journal of applied polymer science, 135(5) 45764, https://doi.org/10.1002/app.45764.
3. [3] Paula, C. T. B, Madeira, A. B, Pereira, P., Branco, R., Morais, P. V., Coelho, J. F. J., Fonseca, A. C., Serra, A. C., (2022) ROS-degradable PEG-based wound dressing films with drug release and antibacterial properties, European Polymer Journal, 177, 111447, https://doi.org/10.1016/j.eurpolymj.2022.111447.
4. [4] Makadia, H. K., Siegel, S. J., (2011) Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier, Polymers, 3(3) 1377-1397, https://www.mdpi.com/2073-4360/3/3/1377.
5. [5] Taşkor Önel, G., (2022) Poly(lactic-co-glycolic acid): FDA and EMA-approved biodegradable elastomeric copolymer, in Recent Approaches in Mathematics and Natural Science, P. Ç. SAYIL (Ed.) Chapter 2, pp. 9-17, Livre De Lyon, Lyon France.
6. [6] Ansari, V, Calore, A., Zonderland, J., Harings, J. A. W., Moroni, L., Bernaerts, K. V., (2022) Additive Manufacturing of α-Amino Acid Based Poly(ester amide)s for Biomedical Applications, Biomacromolecules, 23(3) 1083-1100, https://doi.org/10.1021/acs.biomac.1c01417.
7. [7] Zhao, J., Quan, D., Liao, K., Wu, Q., (2005) PLGA-(L-Asp-alt-diol)x-PLGAs with Different Contents of Pendant Amino Groups: Synthesis and Characterization, Macromolecular Bioscience, 5(7), 636-643, https://doi.org/10.1002/mabi.200500043.
8. [8] Thasneem, Y. M., Rekha, M. R., Sajeesh, S., Sharma, C. P., (2013) Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility, Journal of Colloid and Interface Science, 409, 237-244, https://doi.org/10.1016/j.jcis.2013.07.004.

9. [9] Takeuchi, I., Taniguchi, Y., Tamura, Y., Ochiai, K., Makino, K. (2018) Effects of l-leucine on PLGA microparticles for pulmonary administration prepared using spray drying: Fine particle fraction and phagocytotic ratio of alveolar macrophages, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 537, 411-417, https://doi.org/10.1016/j.colsurfa.2017.10.047.
10. [10] Zhang, C., An, T., Wang, D., Wan, G., Zhang, M., Wang, H., Zhang, S., Li, R., Yang, X., Wang., Y., (2016) Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(β-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma, Journal of Controlled Release, 226, 193-204, https://doi.org/10.1016/j.jconrel.2016.02.030.
11. [11] Clark, A., Milbrandt, T. A., Hilt, J. Z., Puleo, D. A., (2014) Mechanical properties and dual drug delivery application of poly(lactic-co-glycolic acid) scaffolds fabricated with a poly(β-amino ester) porogen, Acta Biomaterialia, 10(5) 2125-2132, https://doi.org/10.1016/j.actbio.2013.12.061.
12. [12] Cui, N., Qian, J., Wang, J., Wang, Y., Xu, W., Wang, H., (2016) Physicochemical properties and biocompatibility of PZL/PLGA/bioglass composite scaffolds for bone tissue engineering, RSC Advances, 6(99) 97096-97106, https://doi.org/10.1039/C6RA20781B.
13. [13] Liu, G., McEnnis, K., (2022) Glass Transition Temperature of PLGA Particles and the Influence on Drug Delivery Applications, Polymers, 14(5) 993, https://doi.org/10.3390/polym14050993.
14. [14] Little, A., Wemyss, A. M., Haddleton, D. M., Tan, B., Sun, Z., Ji, Y., Wan, C.. (2021) Synthesis of Poly(Lactic Acid-co-Glycolic Acid) Copolymers with High Glycolide Ratio by Ring-Opening Polymerisation, Polymers, 13(15) 2458, https://www.mdpi.com/2073-4360/13/15/2458.
15. [15] Yıldırım, Y., (2021) Synthesis and Characterization of Poly(lactic-co-glycolic acid) (PLGA)/Oil Composites, Master, Graduate School of Natural and Applied Sciences Department of Chemical Engineering, Ankara University, 686593, https://dspace.ankara.edu.tr/xmlui/bitstream/handle/20.500.12575/73798/10408913.pdf?sequence=1&isAllowed=y
16. [16] Singh, A., Thotakura, N., Singh, B., Lohan, S., Negi, P., Chitkara, D., Raza, K.. (2019) Delivery of Docetaxel to Brain Employing Piperine-Tagged PLGA-Aspartic Acid Polymeric Micelles: Improved Cytotoxic and Pharmacokinetic Profiles, AAPS PharmSciTech, 20(6) 220, https://doi.org/10.1208/s12249-019-1426-8.
17. [17] Pereira, E. D., Cerruti, R., Fernandes, E., Peña, L., Saez, V., Pinto, J. C., Ramón, J. A., Oliveira, G. E., Gomes de Souza Júnior, F., (2016) Influence of PLGA and PLGA-PEG on the dissolution profile of oxaliplatin, Polímeros, 26, https://doi.org/10.1590/0104-1428.2323.
18. [18] Xiao, H., Wang, L., (2015) Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery, International journal of nanomedicine, 10, 5309-5325, https://doi.org/10.2147/IJN.S85230.
19. [19] Silva, A. T. C. R., Cardoso, B. C. O., Silva, M. E. S. R. e., Freitas, R. F. S., Sousa, R. G., (2015) Synthesis, Characterization, and Study of PLGA Copolymer in Vitro Degradation, Journal of Biomaterials and Nanobiotechnology, 6(1) 12, 52929, https://doi.org/10.4236/jbnb.2015.61002.
20. [20] Erbetta, C. D. A. C., Alves, R. J., Resende, J. M. e., Freitas, R. F. d. S., Sousa, R. G. d., (2012) Synthesis and Characterization of Poly(D, L-Lactide-co-Glycolide) Copolymer, Journal of Biomaterials and Nanobiotechnology, 3(2) 18, 18940, https://doi.org/10.4236/jbnb.2012.32027.
21. [21] Brauner, B., Schuster, C., Wirth, M., Gabor, F., (2020) Trimethoprim-Loaded Microspheres Prepared from Low-Molecular-Weight PLGA as a Potential Drug Delivery System for the Treatment of Urinary Tract