Drug-interactive MPEG--PLA-Phe(Boc) Micelles Enhance the Tolerance and Anti-tumor Efficacy of Docetaxel

Overview

Journal Drug Deliv

Specialty Pharmacology

Date 2020 Feb 1

PMID 32003299

Citations 10

Authors

Feirong Gong

Rongrong Wang

Zhengquan Zhu

Jiayao Duan

Xin Teng

Zhong-Kai Cui

Affiliations

Soon will be listed here.

Abstract

Docetaxel (DTX) is one of the most promising chemotherapeutic agents for a variety of solid tumors. However, the clinical efficacy of the marketed formulation, Taxotere, is limited due to its poor aqueous solubility, side effects caused by the emulsifier, and low selective DTX distribution . Here a facile, well-defined, and easy-to-scale up DTX-loaded -(tert-butoxycarbonyl)--phenylalanine end-capped methoxy-poly(ethylene glycol)--poly(-lactide) (mPEG--PLA-Phe(Boc)) micelles (DTX-PMs) were prepared in an effort to develop a less toxic and more efficacious docetaxel formulation. The physicochemical properties, pharmacokinetics, biodistribution, and anti-tumor efficacy were evaluated in comparison to the marketed DTX formulation Taxotere. DTX was successfully encapsulated in the hydrophobic micellar core with a high encapsulation efficiency (> 95%) and a high drug loading capacity (4.81 ± 0.08%). DTX-PMs exhibited outstanding stability in the aqueous environment due to the strong interactions between the terminal amino acid residues and docetaxel. The pharmacokinetic study in Sprague-Dawley rats revealed higher DTX concentrations in both whole blood and plasma for the group treated with DTX-PMs than that treated with Taxotere due to the improved stability of the micellar formulation. In human non-small cell lung cancer (A549) tumor-bearing Balb/c nude mice, DTX-PMs significantly improved DTX accumulation and stalled DTX elimination in tumors than in bone marrow. Furthermore, only by half of the DTX dosage, our DTX/mPEG-b-PLA-Phe(Boc) micelles can achieve similar therapeutic effects as Taxotere. Altogether, DTX-PMs hold great promise as a simple and effective drug delivery system for cancer chemotherapy.

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References

Gao Y, Chen L, Gu W, Xi Y, Lin L, Li Y . Targeted nanoassembly loaded with docetaxel improves intracellular drug delivery and efficacy in murine breast cancer model. Mol Pharm. 2009; 5(6):1044-54. DOI: 10.1021/mp800072e. View

Wang C, Stayton P, Pun S, Convertine A . Polymer nanostructures synthesized by controlled living polymerization for tumor-targeted drug delivery. J Control Release. 2015; 219:345-354. PMC: 4656053. DOI: 10.1016/j.jconrel.2015.08.054. View

Gonzalez-Fajardo L, Mahajan L, Ndaya D, Hargrove D, Manautou J, Liang B . Reduced in vivo toxicity of doxorubicin by encapsulation in cholesterol-containing self-assembled nanoparticles. Pharmacol Res. 2016; 107:93-101. DOI: 10.1016/j.phrs.2016.03.006. View

Lee S, Yun M, Jeong S, In C, Kim J, Seo M . Development of docetaxel-loaded intravenous formulation, Nanoxel-PM™ using polymer-based delivery system. J Control Release. 2011; 155(2):262-71. DOI: 10.1016/j.jconrel.2011.06.012. View

Gaucher G, Marchessault R, Leroux J . Polyester-based micelles and nanoparticles for the parenteral delivery of taxanes. J Control Release. 2009; 143(1):2-12. DOI: 10.1016/j.jconrel.2009.11.012. View

Sanna V, Roggio A, Posadino A, Cossu A, Marceddu S, Mariani A . Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies. Nanoscale Res Lett. 2011; 6(1):260. PMC: 3211323. DOI: 10.1186/1556-276X-6-260. View

Cho H, Gao J, Kwon G . PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels for drug delivery. J Control Release. 2015; 240:191-201. PMC: 4909590. DOI: 10.1016/j.jconrel.2015.12.015. View

Liu J, Zahedi P, Zeng F, Allen C . Nano-sized assemblies of a PEG-docetaxel conjugate as a formulation strategy for docetaxel. J Pharm Sci. 2007; 97(8):3274-90. DOI: 10.1002/jps.21245. View

Mikhail A, Allen C . Poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelles containing chemically conjugated and physically entrapped docetaxel: synthesis, characterization, and the influence of the drug on micelle morphology. Biomacromolecules. 2010; 11(5):1273-80. DOI: 10.1021/bm100073s. View

10.

Luo Z, Jiang L, Ding C, Hu B, Loh X, Li Z . Surfactant Free Delivery of Docetaxel by Poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate]-Based Polymeric Micelles for Effective Melanoma Treatments. Adv Healthc Mater. 2018; 7(23):e1801221. DOI: 10.1002/adhm.201801221. View

11.

Gong F, Chen D, Teng X, Ge J, Ning X, Shen Y . Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia. Mol Pharm. 2017; 14(8):2585-2594. DOI: 10.1021/acs.molpharmaceut.6b01171. View

12.

Muley P, Kumar S, El Kourati F, Kesharwani S, Tummala H . Hydrophobically modified inulin as an amphiphilic carbohydrate polymer for micellar delivery of paclitaxel for intravenous route. Int J Pharm. 2016; 500(1-2):32-41. DOI: 10.1016/j.ijpharm.2016.01.005. View

13.

Kim K, Park S . Effect of porous silica on sustained release behaviors of pH sensitive pluronic F127/poly(acrylic acid) hydrogels containing tulobuterol. Colloids Surf B Biointerfaces. 2010; 80(2):240-6. DOI: 10.1016/j.colsurfb.2010.06.017. View

14.

Han X, Chen D, Sun J, Zhou J, Li D, Gong F . A novel cabazitaxel-loaded polymeric micelle system with superior in vitro stability and long blood circulation time. J Biomater Sci Polym Ed. 2016; 27(7):626-42. DOI: 10.1080/09205063.2016.1146980. View

15.

Cavallaro G, Craparo E, Sardo C, Lamberti G, Barba A, Dalmoro A . PHEA-PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions. Int J Pharm. 2015; 495(2):719-27. DOI: 10.1016/j.ijpharm.2015.09.050. View

16.

Gothwal A, Khan I, Gupta U . Polymeric Micelles: Recent Advancements in the Delivery of Anticancer Drugs. Pharm Res. 2015; 33(1):18-39. DOI: 10.1007/s11095-015-1784-1. View

17.

Immordino M, Brusa P, Arpicco S, Stella B, Dosio F, Cattel L . Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing docetaxel. J Control Release. 2003; 91(3):417-29. DOI: 10.1016/s0168-3659(03)00271-2. View

18.

Yin Y, Cui F, Mu C, Choi M, Kim J, Chung S . Docetaxel microemulsion for enhanced oral bioavailability: preparation and in vitro and in vivo evaluation. J Control Release. 2009; 140(2):86-94. DOI: 10.1016/j.jconrel.2009.08.015. View

19.

Liu T, Zhang X, Ke B, Wang Y, Wu X, Jiang G . F-127-PEI co-delivering docetaxel and TFPI-2 plasmid for nasopharyngeal cancer therapy. Mater Sci Eng C Mater Biol Appl. 2016; 61:269-77. DOI: 10.1016/j.msec.2015.12.049. View

20.

Muthu M, Kutty R, Luo Z, Xie J, Feng S . Theranostic vitamin E TPGS micelles of transferrin conjugation for targeted co-delivery of docetaxel and ultra bright gold nanoclusters. Biomaterials. 2014; 39:234-48. DOI: 10.1016/j.biomaterials.2014.11.008. View