Synthesis of Three-arm Block Copolymer Poly(lactic--glycolic Acid)-poly(ethylene Glycol) with Oxalyl Chloride and Its Application in Hydrophobic Drug Delivery

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2016 Nov 30

PMID 27895480

Citations 5

Authors

Xiaowei Zhu

Chao Liu

Jianwei Duan

Xiaoyu Liang

Xuanling Li

Hongfan Sun

Deling Kong

Jing Yang

Affiliations

Soon will be listed here.

Abstract

Purpose: Synthesis of star-shaped block copolymer with oxalyl chloride and preparation of micelles to assess the prospect for drug-carrier applications.

Materials And Methods: Three-arm star block copolymers of poly(lactic--glycolic acid) (3S-PLGA)-polyethylene glycol (PEG) were synthesized by ring-opening polymerization, then PEG as the hydrophilic block was linked to the terminal hydroxyl of 3S-PLGA with oxalyl chloride. Fourier-transform infrared (FT-IR) spectroscopy, gel-permeation chromatography (GPC), hydrogen nuclear magnetic resonance (H-NMR) spectra, and differential scanning calorimetry were employed to identify the structure and properties of 3S-PLGA-PEG. Rapamycin (RPM)-loaded micelles were prepared by solvent evaporation, and pyrene was used as the fluorescence probe to detect the critical micelle concentration of the copolymer. The particle size, distribution, and ζ-potential of the micelles were determined by dynamic light scattering, and the morphology of the RPM-loaded micelles was analyzed by transmission electron microscopy. High-performance liquid chromatography was conducted to analyze encapsulation efficiency and drug-loading capacity, as well as the release behavior of RPM-loaded micelles. The biocompatibility of material and the cytostatic effect of RPM-loaded micelles were investigated by Cell Counting Kit 8 assay.

Results: FT-IR, GPC, and H-NMR suggested that 3S-PLGA-PEG was successfully synthesized. The RPM-loaded micelles prepared with the 3S-PLGA-PEG possessed good properties. The micelles had good average diameter and encapsulation efficiency. For in vitro release, RPM was released slowly from 3S-PLGA-PEG micelles, showing that 3S-PLGA-PEG-RPM exhibited a better and longer antiproliferative effect than free RPM.

Conclusion: In this study, we first used oxalyl chloride as the linker to synthesize 3S-PLGA-PEG successfully, and compared with reported literature, this method shortened the reaction procedure and improved the reaction yield. The micelles prepared with this material proved suitable for drug-carrier application.

Citing Articles

Synthesis of Poly(L-lactide)-poly(ε-caprolactone)-poly(ethylene glycol) Terpolymer Grafted onto Partially Oxidized Carbon Nanotube Nanocomposites for Drug Delivery.

Gonzalez-Iniguez K, Figueroa-Ochoa E, Martinez-Richa A, Cajero-Zul L, Nuno-Donlucas S Polymers (Basel). 2024; 16(18).

PMID: 39339044 PMC: 11435386. DOI: 10.3390/polym16182580.

Highly sensitive HO-scavenging nano-bionic system for precise treatment of atherosclerosis.

Liang X, Li H, Li X, Tian X, Zhang A, Luo Q Acta Pharm Sin B. 2023; 13(1):372-389.

PMID: 36815039 PMC: 9939301. DOI: 10.1016/j.apsb.2022.04.002.

ROS-responsive nanoparticle-mediated delivery of CYP2J2 gene for therapeutic angiogenesis in severe hindlimb ischemia.

Gui L, Chen Y, Diao Y, Chen Z, Duan J, Liang X Mater Today Bio. 2022; 13:100192.

PMID: 34988419 PMC: 8695365. DOI: 10.1016/j.mtbio.2021.100192.

Assessment of the Effect of PLGA Co-polymers and PEG on the Formation and Characteristics of PLGA-PEG-PLGA Co-block Polymer Using Statistical Approach.

Sulaiman T, Larasati D, Nugroho A, Choiri S Adv Pharm Bull. 2019; 9(3):382-392.

PMID: 31592431 PMC: 6773940. DOI: 10.15171/apb.2019.045.

Protein delivery nanosystem of six-arm copolymer poly(ε-caprolactone)-poly(ethylene glycol) for long-term sustained release.

Duan J, Liu C, Liang X, Li X, Chen Y, Chen Z Int J Nanomedicine. 2018; 13:2743-2754.

PMID: 29780245 PMC: 5951147. DOI: 10.2147/IJN.S161006.

References

Zheng Y, Li S, Weng Z, Gao C . Hyperbranched polymers: advances from synthesis to applications. Chem Soc Rev. 2015; 44(12):4091-130. DOI: 10.1039/c4cs00528g. View

Yoo H, Park T . Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA-PEG block copolymer. J Control Release. 2001; 70(1-2):63-70. DOI: 10.1016/s0168-3659(00)00340-0. View

Farokhzad O, Cheng J, Teply B, Sherifi I, Jon S, Kantoff P . Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci U S A. 2006; 103(16):6315-20. PMC: 1458875. DOI: 10.1073/pnas.0601755103. View

Vaishya R, Mandal A, Patel S, Mitra A . Extended release microparticle-in-gel formulation of octreotide: Effect of polymer type on acylation of peptide during in vitro release. Int J Pharm. 2015; 496(2):676-88. PMC: 4688050. DOI: 10.1016/j.ijpharm.2015.11.002. View

Mosqueira V, Legrand P, Morgat J, Vert M, Mysiakine E, Gref R . Biodistribution of long-circulating PEG-grafted nanocapsules in mice: effects of PEG chain length and density. Pharm Res. 2001; 18(10):1411-9. DOI: 10.1023/a:1012248721523. View

Albengres E, Le Louet H, Tillement J . Immunosuppressive drugs and pregnancy: experimental and clinical data. Transplant Proc. 1997; 29(5):2461-6. DOI: 10.1016/s0041-1345(97)00450-8. View

Patravale V, Date A, Kulkarni R . Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol. 2004; 56(7):827-40. DOI: 10.1211/0022357023691. View

Mei L, Jiang Y, Feng S . Star-shaped block polymers as a molecular biomaterial for nanomedicine development. Nanomedicine (Lond). 2013; 9(1):9-12. DOI: 10.2217/nnm.13.180. View

Mirza S, Hossain M, Mathews C, Martinez P, Pino P, Gay J . Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine. 2011; 57(1):136-42. PMC: 3270578. DOI: 10.1016/j.cyto.2011.09.029. View

10.

Prasad Bastakoti B, Liao S, Inoue M, Yusa S, Imura M, Nakashima K . pH-responsive polymeric micelles with core-shell-corona architectures as intracellular anti-cancer drug carriers. Sci Technol Adv Mater. 2016; 14(4):044402. PMC: 5090313. DOI: 10.1088/1468-6996/14/4/044402. View

11.

Zhang Y, Kohler N, Zhang M . Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials. 2002; 23(7):1553-61. DOI: 10.1016/s0142-9612(01)00267-8. View

12.

Van Eerdenbrugh B, Van den Mooter G, Augustijns P . Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products. Int J Pharm. 2008; 364(1):64-75. DOI: 10.1016/j.ijpharm.2008.07.023. View

13.

Zhou H, Wan J, Wu L, Yi T, Liu W, Xu H . A new strategy for enhancing the oral bioavailability of drugs with poor water-solubility and low liposolubility based on phospholipid complex and supersaturated SEDDS. PLoS One. 2014; 8(12):e84530. PMC: 3877285. DOI: 10.1371/journal.pone.0084530. View

14.

Cevc G . Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev. 2004; 56(5):675-711. DOI: 10.1016/j.addr.2003.10.028. View

15.

Chen F, Zhang J, He Y, Fang X, Wang Y, Chen M . Glycyrrhetinic acid-decorated and reduction-sensitive micelles to enhance the bioavailability and anti-hepatocellular carcinoma efficacy of tanshinone IIA. Biomater Sci. 2015; 4(1):167-82. DOI: 10.1039/c5bm00224a. View

16.

Kojima C, Kono K, Maruyama K, TAKAGISHI T . Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs. Bioconjug Chem. 2000; 11(6):910-7. DOI: 10.1021/bc0000583. View

17.

He C, Hu Y, Yin L, Tang C, Yin C . Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials. 2010; 31(13):3657-66. DOI: 10.1016/j.biomaterials.2010.01.065. View

18.

Kumari A, Yadav S, Yadav S . Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2009; 75(1):1-18. DOI: 10.1016/j.colsurfb.2009.09.001. View

19.

Merisko-Liversidge E, Liversidge G, Cooper E . Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci. 2003; 18(2):113-20. DOI: 10.1016/s0928-0987(02)00251-8. View

20.

Weber K, Alipui D, Sison C, Bloom O, Quraishi S, Overby M . Serum levels of the proinflammatory cytokine interleukin-6 vary based on diagnoses in individuals with lumbar intervertebral disc diseases. Arthritis Res Ther. 2016; 18:3. PMC: 4718017. DOI: 10.1186/s13075-015-0887-8. View