Study on new ocular drug delivery system

摘要

Ophthalmic drug delivery is one of the important fields of controlled release. The sensitivity and protection mechanism of eye promote more effective drug delivery system with better compliancy to be developed, however, the application of numerous pharmaceutical method are limited simultaneously, which presents great challenge in designing ocular dosage form. In recent years, liposome, nanoparticles, microspheres and microemulsion have received extensive interests.Cationic liposome is a novel drug delivery system in recent years and mainly used as a vector for gene-therapeutic drugs. Because of the electrostatic interaction between the positive charges on the lipid vesicle and the negative charges on surface of the cornea, the cationic liposome can raise the drug's corneal retention time, corneal permeability and bioavailability when used for the treatment of ocular diseases. Solid lipid nanoparticle is developed at early 1990s, now it is a good alternative carrier of traditional colloidal controlled-release drug delivery system. It has many advantages such as good biocompatibility duo to the use of physiological and biodegradable lipids of low systemic toxicity, possibility of production on large industrial and reduce of drug leakage during storage. Some people report that solid lipid nanoparticle drug delivery system can improve ocular bioavailability. Micro emulsion is defined as a dispersion consist of oil, surfactant, cosurfactant and aqueous. Micro emulsion has several advantages such as enhanced drug solubility, good thermodynamic stability, enhancing effect on transdermal ability over conventional formulation.The purpose of this article was to study the preparations and the in vitro release of cationic liposomes, solid lipid nanopaticles and micro emulsion ocular drug delivery system. Ibuprofen was used as a model drug of highly lipophilic. In this work, DC-Chol was synthesized by N', N'-dimethylethylene diamine and cholesterol chloroformate and used as positively charging material in cationic liposome formulation. The Ibuprofen cationic liposome, Ibuprofen solid lipid nanoparticles and Ibuprofen microemulsion were prepared by ethanol-injecting method and melting-ultrasonic method, respectively. The physical-chemical properties such as entrapping efficiency, particle size and zeta potential of the three preparations were characterized and the isolated cornea permeability tests were carried out to reveal the in vitro release of them; The entrapping efficiency of lbuprofen cationic liposome and Ibuprofen solid lipid nanoparticles were 78.3% and 92.5%; particle size and zeta potential of cationic liposome, solid lipid nanoparticles and microemulsion were 163nm, 69nm, 80nm and +44.7mv, -20.2mv, +35. 1mv; the Papp of four test preparations, Ibuprofen cationic liposome, solid lipid nanoparticles, micro emulsion, solid lipid nanoparticles with 0.02% Transcutle P as permeability enhancer were 5.44, 5.51, 4.59 and 6.35 fold in contrast with Ibuprofen eye drops (suspension).All the three microparticles ophthalmic drug delivery systems studied showed no significant irrigation to rabbit eyes and could enhance the isolated corneal permeability of model drug.