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Title: Stimuli-responsive hydrogels for controlled pilocarpine ocular delivery
Authors: Casolaro, Mario 
Casolaro, Ilaria
Lamponi, Stefania 
Keywords: Ionic interactions; Mouse fibroblasts NIH3T3 cell proliferation; Ocular delivery; Pilocarpine; Stimuli-responsive hydrogels
Issue Date: 2012
Project: None 
A series of vinyl hydrogels containing α-aminoacid (L-histidine, L-valine) residues was synthesized and their swelling properties evaluated at different pHs and temperatures. Unlike the zwitterionic compound containing only the L-histidine, a dual-stimuli responsiveness was improved in the carboxyl acid hydrogels carrying the L-valine residues (HVa). Besides the COOH functionality, the presence of either isopropyl and amido groups in the monomer structure renders the hydrogel also temperature-responsive, in a similar manner as the well-known poly(N-isopropylacrylamide) (pNIPAAm). The three HVa hydrogels (crosslinked with 1, 2, and 5 mol% of N,N0-ethylene-bisacrylamide, EBA) show a phase separation at the same critical pH4, although a different swelling was improved by the amount of EBA. In buffered solutions, the effect of increasing temperature led to decrease the swelling and, as the pH is close to the critical one, a further and sharper collapse of the hydrogel may be tuned. The release study of pilocarpine in physiological conditions showed a burst effect within the first few hours, followed by a sustained release for a week. The initial burst effect was strongly dependent on the kind of hydrogel investigated. As the pilocarpine is a basic molecule (pK a 7.2), it may interact more strongly with the free carboxyl groups in the ionized state of the HVa hydrogels than the zwitterionic species of the histidine compounds. The releasing profile shows a three time greater release of the pilocarpine loaded in the HVa hydrogels. The hydrogels were found to be non-toxic against the mouse fibroblast NIH3T3 cells. The presence of pilocarpine strongly increased the cell proliferation even after 2 days.
ISSN: 0939-6411
DOI: 10.1016/j.ejpb.2011.11.013
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