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Self-aggregated nanoparticles based on amphiphilic poly(lactic acid)-grafted-chitosan copolymer for ocular delivery of amphotericin B

Authors Zhou WJ, Wang YY, Jian JY, Song SF

Received 7 July 2013

Accepted for publication 21 August 2013

Published 27 September 2013 Volume 2013:8(1) Pages 3715—3728

DOI https://doi.org/10.2147/IJN.S51186

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Wenjun Zhou,1 Yuanyuan Wang,2 Jiuying Jian,2 Shengfang Song1

1Department of Ophthalmology, Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Life Science, Chongqing Medical University, Chongqing, People’s Republic of China

Background: The purpose of this study was to develop a self-aggregated nanoparticulate vehicle using an amphiphilic poly(lactic acid)-grafted-chitosan (PLA-g-CS) copolymer and to evaluate its potential for ocular delivery of amphotericin B.
Methods: A PLA-g-CS copolymer was synthesized via a “protection-graft-deprotection” procedure and its structure was confirmed by Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, and X-ray diffraction spectra. Amphotericin B-loaded nanoparticles based on PLA-g-CS (AmB/PLA-g-CS) were prepared by the dialysis method and characterized for particle size, zeta potential, and encapsulation efficiency. Studies of these AmB/PLA-g-CS nanoparticles, including their mucoadhesive strength, drug release properties, antifungal activity, ocular irritation, ocular pharmacokinetics, and corneal penetration were performed in vitro and in vivo.
Results: Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, and X-ray diffraction spectra showed that the PLA chains were successfully grafted onto chitosan molecules and that crystallization of chitosan was suppressed. The self-aggregated PLA-g-CS nanoparticles had a core-shell structure with an average particle size of approximately 200 nm and zeta potentials higher than 30 mV. Amphotericin B was incorporated into the hydrophobic core of the nanoparticles with high encapsulation efficiency. Sustained drug release from the nanoparticles was observed in vitro. The ocular irritation study showed no sign of irritation after instillation of the PLA-g-CS nanoparticles into rabbit eyes. The minimal inhibitory concentration of the AmB/PLA-g-CS nanoparticles showed antifungal activity similar to that of free amphotericin B against Candida albicans. The in vivo ocular pharmacokinetic study suggested that the PLA-g-CS nanoparticles have the advantage of prolonging residence time at the ocular surface. The corneal penetration study showed that the PLA-g-CS nanoparticles could penetrate into the cornea.
Conclusion: Our results suggest that this nanoparticulate vehicle based on a PLA-g-CS copolymer might be a promising system for effective ocular delivery of amphotericin B.

Keywords: chitosan, poly(lactic acid), nanoparticles, amphotericin B

 

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