Pluronic F127-based ocular delivery system containing biodegradable polyisobutylcyanoacrylate nanocapsules of pilocarpine.
The objectives of our study were to prepare a biodegradable polyisobutylcyanoacrylate (PIBCA) colloidal particulate system of pilocarpine, to incorporate it into a Pluronic F127(PF127)-based gel delivery system, and to evaluate its ability to prolong the release of pilocarpine. Polyisobutylcyanoacrylate nanocapsules (PIBCA-NC) of pilocarpine were prepared by interfacial polymerization. Physicochemical characterization of the colloidal dispersion of PIBCA-NC of pilocarpine was performed by measuring drug loading, particle size analysis, and scanning electron microscopy. Results indicated that approximately 13.5% of pilocarpine was loaded onto the PIBCA-NC, the nanocapsules ranged from 370 to 460 nm, the distribution was narrow, and there was no significant effect of stirring speed on particle size. The PIBCA-NC dispersion of 1% pilocarpine alone (I) and after incorporation into the Pluronic F127 gel delivery system (II) were compared against 1% pilocarpine incorporated into a PF127 gel containing 5% methylcellulose (PF127MC) alone (III) by measuring the miotic response in the albino rabbit eye. Statistical analysis indicated a rank-order for both the duration and intensity of miosis of II > III >> I, with all differences being significant (p < 0.05). Thus, it appears that II increases the contact time of pilocarpine with the absorbing tissue in the eye, thereby improving ocular bioavailability. The PIBCA-NC of pilocarpine dispersed in the PF127MC gel delivery system has considerable potential for achieving a prolonged delivery for such drugs as pilocarpine and other more hydrophobic drugs.
Desai
S D
SD
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Blanchard
J
J
D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D003487:Cyanoacrylates; D016503:Drug Delivery Systems; D004659:Enbucrilate; D005079:Excipients; D005123:Eye / Q000378:metabolism*; D008297:Male; D008855:Microscopy, Electron, Scanning; D015877:Miosis / Q000139:chemically induced; D008916:Miotics / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010862:Pilocarpine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D020442:Poloxamer; D011108:Polymers; D011817:Rabbits
D003487:Cyanoacrylates; D005079:Excipients; D008916:Miotics; D011108:Polymers; D010862:Pilocarpine; D020442:Poloxamer; D004659:Enbucrilate