Design and characterization of a novel amphiphilic chitosan nanocapsule-based thermo-gelling biogel with sustained in vivo release of the hydrophilic anti-epilepsy drug ethosuximide.
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.
Department of Materials Science and Engineering, National Chiao Tung University, 1001 Ta-Hseuh Road, Hsinchu City, 300 Taiwan, ROC.
Meng-Hsuan
MH
Hsiao
Mikael
M
Larsson
Anette
A
Larsson
Hanne
H
Evenbratt
Ying-Yu
YY
Chen
You-Yin
YY
Chen
Dean-Mo
DM
Liu
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D005013:Ethosuximide / Q000008:administration & dosage / Q000737:chemistry*; D005782:Gels; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D020318:Rats, Long-Evans; D012640:Seizures / Q000188:drug therapy
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D053769:Nanocapsules; D005013:Ethosuximide; D048271:Chitosan