Indometacin-loaded micelles based on star-shaped PLLA-TPGS copolymers: effect of arm numbers on drug delivery
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Star-shaped copolymers based on star-shaped poly (L-lactide) (s-PLLA) and tocopheryl polyethylene glycol 1000 succinate (TPGS) (s-PLLA-TPGS) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of s-PLLA-TPGS copolymers and their micelle properties. The structure and Mw of s-PLLA-TPGS were characterized with 1H NMR, GPC, DSC, and XRD. The indometacin(IMC)-loaded s-PLLA-TPGS micelles were obtained by dialysis method. The effects of arm numbers of s-PLLA-TPGS copolymers on surface morphology, particle size, zeta potential, drug loading content (LC), drug encapsulation efficiency (EE), and in vitro drug release behavior of prepared micelles were studied. The results indicated that the average diameters, LC, and EE of IMC-loaded s-PLLA-TPGS micelles gradually increased in the order of 4-arm, 5-arm, and 6-arm s-PLLA-TPGS copolymers. The in vitro release studies showed that the IMC accumulative release can be decreased by increasing the arm numbers of the s-PLLA-TPGS copolymers, and the release profiles of IMC from the s-PLLA-TPGS copolymers followed the Baker-Lonsdale model equation. The results suggest that the arm number regulation of s-PLLA-TPGS copolymers can provide a new strategy for designing drug carriers of high efficiency.
KeywordsStar-shaped copolymers s-PLLA-TPGS Micelles Indometacin Drug release system
Conflict of interest
The authors declare that they have no conflict of interest.
This work was financed by National Natural Science Foundation of China (Grant No.51602001), Anhui Provincial Natural Science Foundation (1608085QE106) and Scientific Research Fund of Anhui Provincial Education Department (KJ2017A030, KJ2018A0038).
Compliance with ethical standards
The work described has not been published previously and not under consideration for publication elsewhere, in whole or in part.
- 4.Wu BQ, Liang Y, Tan Y, Xie CM, Shen J, Zhang M, Liu XK, Yang LX, Zhang FJ, Liu L (2016) Genistein-loaded nanoparticles of star-shaped diblock copolymer mannitol-core PLGA-TPGS for the treatment of liver cancer. Mater Sci Eng C 59:792–800. https://doi.org/10.1016/j.msec.2015.10.087 CrossRefGoogle Scholar
- 6.Zeng XW, Tao W, Mei L, Huang LG, Tan CY, Feng SS (2013) Cholic acid-functionalized nanoparticles of star-shaped PLGA-vitamin E TPGS copolymer for docetaxel delivery to cervical cancer. Biomaterials 34(25):6058–6067. https://doi.org/10.1016/j.biomaterials.2013.04.052 CrossRefGoogle Scholar
- 12.Li XJ, Qian YF, Liu T, Hu XL, Zhang GY, You YZ, Liu SY (2011) Amphiphilic multiarm star block copolymer-based multifunctional unimolecular micelles for cancer targeted drug delivery and MR imaging. Biomaterials 32(27):6595–6605. https://doi.org/10.1016/j.biomaterials.2011.05.049 CrossRefGoogle Scholar
- 14.Peng CL, Shieh MJ, Tsai MH, Chang CC, Lai PS (2008) Self-assembled star-shaped chlorin-core poly(ɛ-caprolactone)–poly(ethylene glycol) diblock copolymer micelles for dual chemo-photodynamic therapies. Biomaterials 29(26):3599–3608. https://doi.org/10.1016/j.biomaterials.2008.05.018 CrossRefGoogle Scholar
- 16.Garofalo C, Capuano G, Sottile R, Tallerico R, Adami R, Reverchon E, Carbone E, Izzo L, Pappalardo D (2014) Different insight into amphiphilic PEG-PLA copolymers: influence of macromolecular architecture on the micelle formation and cellular uptake. Biomacromolecules 15(1):403–415. https://doi.org/10.1021/bm401812r CrossRefGoogle Scholar
- 19.Park W, Kim D, Hang HC, Bae YH, Na K (2012) Multi-arm histidine copolymer for controlled release of insulin from poly(lactide-co-glycolide) microsphere. Biomaterials 33(34):8848–8857. https://doi.org/10.1016/j.biomaterials.2012.08.042 CrossRefGoogle Scholar
- 24.Pan J, Feng SS (2008) Targeted delivery of paclitaxel using folate-decorated poly(lactide)-vitamin E TPGS nanoparticles. Biomaterials 29(17):2663–2672. https://doi.org/10.1016/j.biomaterials.2008.02.020 CrossRefGoogle Scholar
- 25.Hua C, Dong CM (2007) Synthesis, characterization, effect of architecture on crystallization of biodegradable poly(epsilon-caprolactone)-b-poly(ethylene oxide) copolymers with different arms and nanoparticles thereof. J Biomed Mater Res A 82A(3):689–700. https://doi.org/10.1002/jbm.a.31167 CrossRefGoogle Scholar
- 27.Lim HJ, Lee H, Kim KH, Huh J, Ahn CH, Kim JW (2013) Effect of molecular architecture on micellization, drug loading and releasing of multi-armed poly(ethylene glycol)-b-poly(ε-caprolactone) star polymers. Colloid Polym Sci 291(8):1817–1827. https://doi.org/10.1007/s00396-013-2916-y CrossRefGoogle Scholar
- 32.Runnel R, Mäkinen KK, Honkala S, Olak J, Mäkinen PL, Nõmmela R, Vahlberg T, Honkala E, Saag M (2013) Effect of three-year consumption of erythritol, xylitol and sorbitol candies on various plaque and salivary caries-related variables. J Dent 41(12):1236–1244. https://doi.org/10.1016/j.jdent.2013.09.007 CrossRefGoogle Scholar
- 33.Ghassemi AH, van Steenbergen MJ, Talsma H, van Nostrum CF, Jiskoot W, Crommelin DJ, Hennink WE (2009) Preparation and characterization of protein loaded microspheres based on a hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid). J Control Release 138(1):57–63. https://doi.org/10.1016/j.jconrel.2009.04.025 CrossRefGoogle Scholar
- 36.Zhang Z, Feng SS (2006) Nanoparticles of poly(lactide)/vitamin E TPGS copolymer for cancer chemotherapy: synthesis, formulation, characterization and in vitro drug release. Biomaterials 27(2):262–270. https://doi.org/10.1016/j.biomaterials.2005.05.104 CrossRefGoogle Scholar
- 37.Siepmann J, Siepmann F (2012) Modeling of diffusion controlled drug delivery. J Control Release 161(2):51–362. https://doi.org/10.1016/j.jconrel2011.10.006
- 39.Ma C, Pan P, Shan G, Bao Y, Fujita M, Maeda M (2015) Core-shell structure, biodegradation, and drug release behavior of poly(lactic acid)/poly(ethylene glycol) block copolymer micelles tuned by macromolecular stereostructure. Langmuir 31(4):1527–1536. https://doi.org/10.1021/la503869d CrossRefGoogle Scholar
- 42.Hussain H, Tan BH, Gudipati CS, Liu Y, He CB, Davis TP (2008) Synthesis and self-assembly of poly(styrene)-b-poly(N-vinylpyrrolidone) amphiphilic diblock copolymers made via a combined ATRP and MADIX approach. J Polym Sci Part A Pol Chem 46(16):5604–5615. https://doi.org/10.1002/pola.22882 CrossRefGoogle Scholar
- 48.Zhang CN, Wang W, Liu T, Wu YK, Guo H, Wang P, Tian Q, Wang YM, Yuan Z (2012) Doxorubicin-loaded glycyrrhetinic acid-modified alginate nanoparticles for liver tumor chemotherapy. Biomaterials 33(7):2187–2196. https://doi.org/10.1016/j.biomaterials.2011.11.045 CrossRefGoogle Scholar
- 50.Nguyen HN, Ha PT, Sao Nguyen AS, Nguyen DT, Do HD, Thi QN, Thi MNH (2016) Curcumin as fluorescent probe for directly monitoring in vitro uptake of curcumin combined paclitaxel loaded PLA-TPGS nanoparticles. Adv Nat Sci Nanosci Nanotechnol 7(2):025001. https://doi.org/10.1088/2043-6262/7/2/025001 CrossRefGoogle Scholar
- 53.D'Aurizio E, van Nostrum CF, van Steenbergen MJ, Sozio P, Siepmann F, Siepmann J, Hennink WE, Di Stefano A (2011) Preparation and characterization of poly(lactic-co-glycolic acid) microspheres loaded with a labile antiparkinson prodrug. Int J Pharm 409(1–2):289–296. https://doi.org/10.1016/j.ijpharm.2011.02.036 CrossRefGoogle Scholar
- 54.Shi XX, Ma XQ, Hou ML, Gao YE, Bai S, Xiao B, Xue P, Kang YJ, Xu ZG, Li CM (2017) pH-responsive unimolecular micelles based on amphiphilic star-like copolymer with high drug loading for effective drug delivery and cellular imaging. J Mater Chem 5(33). https://doi.org/10.1039/c7tb01477e