Journal
JOURNAL OF CONTROLLED RELEASE
Volume 161, Issue 3, Pages 942-948Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2012.05.038
Keywords
Amphiphilic chitosan; Drug delivery; Nano capsules; Thermo responsive; In vivo
Funding
- National Science Council, Taiwan, Republic of China [NSC 99-2113-M-009-013-MY2-3060]
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Thermo-gelling injectable nanogels, with no burst release of loaded drug, were prepared by a simple route by combining self assembled nanocapsules of amphiphilically modified chitosan with glycerophosphate di-sodium salt and glycerol. The potential as a depot drug delivery system was demonstrated in vivo through the therapeutic effect of ethosuximide (ESM) loaded nanogels, suppressing spike wave discharges (SWDs) in Long Evan rat model. Simultaneously clearance of gels from the site of administration was monitored non-invasively using MRI. The gel structure was characterized using TEM and SEM, confirming the gels to be an assembly of nanocapsules and using two-photon microscopy to visualize the network structure. In vitro drug release studies using ESM revealed that the nanogels exhibited extended, mostly Fickian release. Finally, all investigated formulations displayed excellent cytotoxicity data determined by MTT assay using human retinal pigmented epithelium cells. All presented properties are highly desirable for injectable depot gels for drug delivery. (c) 2012 Elsevier B.V. All rights reserved.
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