title: Ocular permeability of pirenzepine hydrochloride enhanced by methoxy poly(ethylene glycol)-poly(D, L-lactide) block copolymer.
abstract: Methoxy poly(ethylene glycol)-poly(D, L-lactide) block copolymer was tested as an ocular permeation enhancer for pirenzepine hydrochloride. The block copolymers with the methoxy poly(ethylene glycol) to poly(D, L-lactide) weight ratio of 80/20, 50/50, 40/60 were synthesized by a ring-opening polymerization procedure. In vitro transcorneal experiments demonstrated that the block copolymer 80/20 significantly enhanced the transcorneal permeation of pirenzepine at the mass ratio of 1/1.4 (pirenzepine hydrochloride/copolymer). Interaction between pirenzepine and copolymer was identified by infrared spectroscopy analysis and dialysis experiments. Ocular pharmacokinetics of pirenzepine/copolymer preparation by in vivo instillation experiments confirmed that block copolymer could enhance the ocular penetration of pirenzepine. Ocular chronic toxicity experiments of block copolymer and pirenzepine/copolymer preparation were studied on rabbits, and no significant toxicity in both groups was observed within 9 months. It could conclude that pirenzepine/copolymer preparation is effective and safe in ocular delivery of pirenzepine.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P. R. China. jiashengtu@cpu.edu.cn
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Tu
authors.forename: Hui
authors.initials: H
authors.lastname: Pang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.forename: Pengmei
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D003315:Cornea / Q000378:metabolism*; D004337:Drug Carriers; D005260:Female; D008297:Male; D008823:Micelles; D010316:Particle Size; D010539:Permeability; D010890:Pirenzepine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D010890:Pirenzepine; D011092:Polyethylene Glycols