Investigation of polymeric nanoparticles as carriers of enalaprilat for oral administration.
Enalaprilat is a typical angiotensin-converting enzyme inhibitor and is very poorly absorbed from the gastrointestinal tract. The aim of this study was to design and characterize poly-(lactide-co-glycolide) (PLGA) and polymethylmethacrylate (PMMA) nanoparticles containing enalaprilat and to evaluate the potential of these colloidal carriers for the transport of drugs through the intestinal mucosa. Nanoparticle dispersions were prepared by the emulsification-diffusion method and characterized according to particle size, zeta potential, entrapment efficiency and physical stability. Effective permeabilities through rat jejunum of enalaprilat in solution and in enalaprilat-loaded nanoparticles were compared using side-by-side diffusion chambers. The solubility of enalaprilat is very low in many acceptable organic solvents, but in benzyl alcohol is sufficient to enable the production of nanoparticles by the emulsification-diffusion process. The diameters of drug-loaded PMMA and PLGA nanoparticles were 297 and 204 nm, respectively. The concentration of the stabilizer polyvinyl alcohol (PVA) in dispersion has an influence on particle size but not on drug entrapment. The type of polymer has a decisive influence on drug content--7 and 13% for PMMA and PLGA nanoparticles, respectively. In vitro release studies show a biphasic release of enalaprilat from nanoparticle dispersions-fast in the first step and very slow in the second. The apparent permeability coefficient across rat jejunum of enalaprilat entrapped in PLGA nanoparticles is not significantly improved compared with enalaprilat in solution.
Ahlin
P
P
University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia.
Kristl
J
J
Kristl
A
A
Vrecer
F
F
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D004058:Diffusion; D004337:Drug Carriers; D015773:Enalaprilat / Q000008:administration & dosage*; D005079:Excipients; D005612:Freeze Drying; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid; D008863:Microspheres; D010539:Permeability; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D019904:Polymethyl Methacrylate; D051381:Rats; D012996:Solutions; D012997:Solvents
D000806:Angiotensin-Converting Enzyme Inhibitors; D004337:Drug Carriers; D005079:Excipients; D011108:Polymers; D012996:Solutions; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019904:Polymethyl Methacrylate; D015773:Enalaprilat