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

Circumventing the blood–brain barrier: Local delivery of cyclosporin A stimulates stem cells in stroke-injured rat brain

“…CsA (Cat.# C-6000, LC Laboratories, Woburn, MA, USA) was encapsulated in PLGA (acid-terminated 50:50, MW 7,000-17,000, Cat.# 71989) microparticles using a singlephase oil/water emulsion solvent evaporation technique, as described previously [15]. Blank PLGA particles were similarly prepared without the addition of CsA in the organic phase.…”

“…It is injectable, gels rapidly at physiological temperatures, and is bioresorbable [9]. HAMC can be used alone [10][11][12][13] or in combination with drug-loaded polymeric particles [7,14,15] to deliver therapeutics to the CNS. In the mouse brain, an epi-cortical delivery strategy was used to inject HAMC for local drug release of bioactive drug without damage to brain tissue [7,12,13,15] (Fig.…”

Central Nervous System

“…Phase 2 clinical trials are ongoing for a combination of bolus injection and continuous infusion after TBI (CHIC, NCT01825044) or a single bolus injection after stroke (CsAStroke, NCT01527240). Although these efforts may be plagued by off-target side effects of immune suppression seen with corticosteroids, future success may be seen with nonimmunosuppressant analogues targeting antiapoptotic pathways (e.g., NIM811 [64]) or local delivery methods that avoid off-target effects [65].…”

Biomaterials Application in Stem Cell Therapies for Stroke

“…Alternatively, a variety of sustained-release strategies could be employed. Cyclosporine A, a potent anti-inflammatory drug, has been incorporated into PLGA microspheres or HA-methylcellulose composites as drug reservoirs and slowly released over the brain cortex [95]. PLGA particles have been further used to deliver dexamethasone, another potent immunosuppressor, to the CNS [96].…”