PLA-PEG DIBLOCK COPOLYMER MICELLE AS NANOCARRIER FOR ANTI-OBESITY DRUG DELIVERY SYSTEM

Main Article Content

Article Sidebar

Published Oct 9, 2021
Anwarul Azim Akib
Mahamudul Hasan Rumon Md. Moniruzzaman
Al-Nakib Chowdhury Chanchal Kumar Roy

Abstract

Obesity is responsible for thirteen different types of cancers, type-2 diabetes as well as cardiovascular diseases, which leads to approximately 4.7 million premature deaths worldwide in a year [1,2]. Researchers are always working to overcome this health risk by introducing us to new approaches such as various exercises, diet plans, anti-obesity medications, and so on. Despite having a number of available anti-obesity drugs, the efficacy of many orally administered drugs is often limited by their potential to reach the site of therapeutic action due to poor solubility, whereas solubility is a significant physicochemical property of a drug. Depending upon the solubility of drugs, only a small amount of the administered dose may reach the target site, while the remaining amount is distributed in the body, which gives rise to side effects [3]. Herein, we introduce a conjugated polymer nanocarrier consisting of polyethylene glycol–block-polylactic acid (PEG-b-PLA) to transport an anti-obesity drug named "Fenofibrate". The copolymer PEG-b-PLA is amphiphilic in nature and can undergo the self-assembling process in aqueous media that leads to micelles formation during the addition of water above the critical micelle concentration (CMC) [4]. The PEG-b-PLA polymer micelles (PMs) can improve hydrophobic drug loading while also reducing burst effect, avoiding phagocytic engulfment, increasing drug circulation time in the blood, and improving bioavailability [8,9]. Additionally, their tiny particle size allows them to reach the target location, which enhances the efficacy of drugs and reduces toxicity [10]. Moreover, the degradation products from PLA-b-PEG can be excreted by the kidney or enter the Krebs cycle and thus are non-toxic [9]. Although PEG-b-PLA polymer micelle has been used for the treatment of many anticancer drugs, it isn't used for the treatment of anti-obesity drugs yet [11]. In this work, the PEG-b-PLA is synthesized by direct polycondensation of L-lactic acid [12] instead of ring-opening of lactide and further reacted with dihydroxy poly (ethylene glycol) (PEG) in the presence of the Sn(Oct)2 catalyst. Furthermore, the micelles are induced to form by adding water dropwise to the PEG-b-PLA/THF solution. Then, the drug loading and the drug release profile of the poorly water-soluble anti-obesity drug fenofibrate are analyzed and compared. Structurally, the PLA-PEG block copolymer contains two unique polymer domains, a) hydrophobic PLA and b) hydrophilic PEG. The hydrophobic PLA encapsulates the hydrophobic drugs inside the polymer micelle due to the hydrophobic-hydrophobic interaction. On the other hand, the hydrophilic PEG protects the micelle from enzymatic degradation and makes the drug more water-soluble. We observed the UV absorbance of the drug-loaded micelle increased remarkably compared to the free drugs during the study. This indicates that the PLA-b-PEG micelle has a higher ability to solubilize low water-soluble fenofibrate drugs. Moreover, the drug loading and drug release of the micelle were ensured by the dynamic light scattering (DLS). The encapsulation efficiency and the drug release percentage of the polymer micelle at pH 7.4 (blood) and pH 6.5 (intestine) are determined by a spectroscopic technique. Additionally, the obtained PLA-PEG polymer is further confirmed by the FT-IR analysis, and the formation of the micelles was ensured from DLS testing, which indicates PLA-PEG can be used as a potential nanocarrier for anti-obesity drugs in the near future. A schematic overview of the whole process is shown in figure 1.

How to Cite

Akib, A. A., Rumon, M. H., Md. Moniruzzaman, Chowdhury, A.-N., & Roy, C. K. (2021). PLA-PEG DIBLOCK COPOLYMER MICELLE AS NANOCARRIER FOR ANTI-OBESITY DRUG DELIVERY SYSTEM. SPAST Abstracts, 1(01). Retrieved from https://spast.org/techrep/article/view/1901
Abstract 218 |

Article Details

Keywords

polymer micelle, obesity, hydrophobic drug, poor solubility, pH-sensitive, drug loading, drug release, nanocarrier

References
[1] C. A. Gilbert, J. M. Slingerland, Annual Review of Medicine, 64(1), 45–57, 2013. doi:10.1146/annurev-med-121211-091527
[2] C. Cercato, F. A. Fonseca, Diabetol Metab Syndr 11, 74 (2019). https://doi.org/10.1186/s13098-019-0468-0
[3] J. G. Kang, C. Y. Park, Diabetes & Metabolism Journal, 36(1), 13, (2012). doi:10.4093/dmj.2012.36.1.13
[4] D. Lombardo, M. A. Kiselev, S. Magazù, P. Calandra, Advances in Condensed Matter Physics, 2015, 1–22. doi:10.1155/2015/151683
[5] G. S. Kwon, T. Okano, Advanced Drug Delivery Reviews, 21(2), 107–116, (1996). doi:10.1016/s0169-409x(96)00401-2
[6] R. T. Liggins, H. M., Burt, Advanced Drug Delivery Reviews, 54(2), 191–202, (2002). doi:10.1016/s0169-409x(02)00016-9
[7] A. A. Ignatius, L. E. Claes, Biomaterials, 17(8), 831–839, (1996). doi:10.1016/0142-9612(96)81421-9
[8] G. S. Kwon, K. Kataoka, Advanced Drug Delivery Reviews, 16(2-3), 295–309, (1995). doi:10.1016/0169-409x(95)00031-2
[9] K. Kataoka, A, Harada, Y. Nagasaki, Advanced Drug Delivery Reviews, 47(1), 113–131, (2001). doi:10.1016/s0169-409x(00)00124-1
[10] R. Z. Xiao, Z. Zeng, G. L. Zhou, J. J. Wang, F. Z. Li, A. M. Wang, International Journal of Nanomedicine, 1057, (2010). doi:10.2147/ijn.s14912
[11] Z. Hami, M. Amini, M. Ghazi-Khansari, S. Rezayat, K. Gilani, DARU Journal of Pharmaceutical Sciences, 22(1), 30, (2014). doi:10.1186/2008-2231-22-30
[12] Y. Zhao, Z. Wang, F. Yang, Journal of Applied Polymer Science, 97(1), 195–200,(2005). doi:10.1002/app.21746
Section
NS2: Chemistry