Design of an anti-inflammatory composite nanosystem and evaluation of its potential for ocular drug delivery

被引:10
|
作者
Du Toit, Lisa C. [1 ]
Govender, Thirumala [2 ]
Carmichael, Trevor [3 ]
Kumar, Pradeep [1 ]
Choonara, Yahya E. [1 ]
Pillay, Viness [1 ]
机构
[1] Univ Witwatersrand, Dept Pharm & Pharmacol, ZA-2193 Johannesburg, South Africa
[2] Univ KwaZulu Natal, Dept Pharmaceut Sci, ZA-4041 Durban, South Africa
[3] Univ Witwatersrand, Dept Neurosci, Div Ophthalmol, ZA-2193 Johannesburg, South Africa
关键词
ophthalmic drug delivery; nanotechnology; nanoparticles; lipids; liposomes; permeation; cell uptake; ELISA; confocal microscopy; computational modeling; NF-KAPPA-B; LOADED ALBUMIN NANOPARTICLES; CHITOSAN NANOPARTICLES; LIPOSOMES; RELEASE; NANOTECHNOLOGY; MODULATION; PATHWAYS; CARRIERS; SYSTEMS;
D O I
10.1002/jps.23650
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
This study compared two specific embodiments of an ocular nanosystem (NS): one portraying a purely polymeric system, referred to as the chitosan-poly(epsilon-caprolactone) nanosystem, and the other based on a composite lipoidal-polymeric NS architecture utilizing phospholipidsthe lipoidal-chitosan-poly(epsilon-caprolactone) nanosystem. Investigations undertaken were implicit to warrant inclusion in an implantable system for the intelligent treatment of inflammatory disorders (specifically ocular afflictions). Results obtained highlighted the enhanced efficacy of both NS to an indomethacin suspension in terms of tissue permeation, cell uptake, and anti-inflammatory activity. Furthermore, the size (134.3 vs. 140.7 nm); surface charge (+49.4 vs. +55.7 mV); drug incorporation efficiency (75.00% vs. 67.20%); flux across the retinal pigment epithelium-choroid-sclera (0.002951 vs. 0.001255 mg cm (-2) h(-1)); anti-inflammatory efficacy, demonstrated by a decrease in 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole complex formation (0.0031 vs. 0.0023 mmol L-1) and decrease in NFB formation (decrease in relative optical density of 0.2027 vs. 0.2420); and enhanced inflammatory cell uptake, visualized via high-speed fluorescence and confocal microscopy, all highlighted the enhanced potential of the lipoidal system compared with the purely polymeric NS for potentially targeting inflammatory disorders of the posterior segment of the eye. Mechanics energy relationships revealed the favorable hydrophilic-lipophilic balance of the composite NS compared with the purely polymeric NS. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2780-2805, 2013
引用
收藏
页码:2780 / 2805
页数:26
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