Skip to Content
Merck
  • A hydrogel composite system for sustained epi-cortical delivery of Cyclosporin A to the brain for treatment of stroke.

A hydrogel composite system for sustained epi-cortical delivery of Cyclosporin A to the brain for treatment of stroke.

Journal of controlled release : official journal of the Controlled Release Society (2013-01-12)
Matthew J Caicco, Michael J Cooke, Yuanfei Wang, Anup Tuladhar, Cindi M Morshead, Molly S Shoichet
ABSTRACT

Stimulation of endogenous neural stem/progenitor cells (NSPCs) with therapeutic factors holds potential for the treatment of stroke. Cyclosporin A (CsA) is a particularly promising candidate molecule because it has been shown to act as a survival factor for these cells over a period of weeks both in vitro and in vivo; however, systemically-delivered CsA compromises the entire immune system, necessitating sustained localized delivery. Herein we describe a local delivery strategy for CsA using an epi-cortical hydrogel of hyaluronan-methylcellulose (HAMC) as the drug reservoir. Three methods of incorporating the drug into the hydrogel (solubilized, particulate, and poly(lactic-co-glycolic) acid (PLGA) microsphere-encapsulated) resulted in tunable release, spanning a period of hours to weeks. Importantly, PLGA-encapsulated CsA released from the hydrogel had equivalent bioactivity to fresh drug as measured by the neurosphere assay. Moreover, when CsA was released from the PLGA/HAMC composite that was injected on the cortex of adult mice, CsA was detected in the NSPC niche at a constant concentration for at least 24days post-implant. Thus this hydrogel composite system may be promising for the treatment of stroke.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methyl cellulose, medium viscosity, Methoxyl content 27.5-31.5 %
Sigma-Aldrich
Methyl cellulose, tested according to Ph. Eur.
Sigma-Aldrich
Methyl cellulose, viscosity: 25 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 1,500 cP
Sigma-Aldrich
Methyl cellulose, 26.0-33.0% (Methoxy group (dry basis)), meets USP testing specifications, viscosity: 1,500 cP
Sigma-Aldrich
Methyl cellulose, meets USP testing specifications, 26.0-33.0% (methoxyl group, on Dry Basis), viscosity: 400 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 4,000 cP
Sigma-Aldrich
Methyl cellulose, 27.5-31.5% (Methoxyl content), viscosity: 400 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 15 cP, BioReagent, suitable for cell culture
Sigma-Aldrich
Methyl cellulose, viscosity: 15 cP
Sigma-Aldrich
Methyl cellulose, viscosity 3000-5500 mPa.s, 2 % in H2O(20 °C)
Sigma-Aldrich
Methyl cellulose, 27.5-31.5% methoxyl basis