International Journal of Pharmaceutics 2014-08-25

In vitro and in vivo evaluation of chitosan graft glyceryl monooleate as peroral delivery carrier of enoxaparin.

Linlin Wang, Liang Li, Yujiao Sun, Jiaojiao Ding, Jinfeng Li, Xiaopin Duan, Yaping Li, Varaporn B Junyaprasert, Shirui Mao

Index: Int. J. Pharm. 471(1-2) , 391-9, (2014)

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Abstract

In this paper a novel copolymer, chitosan graft glyceryl monooleate (CS-GO) was synthesized and its potential as the nanocarrier for enhancing the peroral delivery of enoxaparin was studied systemically. The successful synthesis was characterized by (1)H NMR. Enoxaparin nanocomplexes were prepared by self-assembly. Mucoadhesive properties of the nanocomplexes were evaluated using mucin particle method. Uptake and transport of the nanocomplexes were investigated in Caco-2 cells. In vivo absorption was studied in rats. The therapeutic effects of the nanocomplexes were evaluated using pulmonary thromboembolism model in mice. This study demonstrated that compared to chitosan based system, hydrophobic modification of CS with GO enhanced the oral absorption of enoxaparin significantly, which is in good agreement with the enhanced mucoadhesion, cellular internalization and transport in cell culture. Cellular uptake of CS-GO based enoxaparin nanocomplexes was incubation time, enoxaparin concentration and incubation temperature dependent. The uptake mechanism was assumed to be adsorptive endocytosis via clathrin- and caveolae-mediated process. Its therapeutic efficacy was further demonstrated by pharmacodynamic study with pulmonary thromboembolism inhibition percentage 47.1%. In conclusion, CS-GO copolymer is a promising nanocarrier for enhancing the oral absorption of enoxaparin. Copyright © 2014 Elsevier B.V. All rights reserved.