Preparation and Characterization of Enalapril Maleate-Loaded Nanoparticles Using Amphiphilic Diblock Copolymers

摘要

Nanoparticles with the dimensions of circa 50 nm prepared from the micellar aggregation of diblock copolymers of poly(ethylene oxide) and polycaprolactone (PEO-b-PCL) were explored as a parenteral carrier system for water-soluble organic drugs in salt form.Enalapril maleate (EPM),developed for hypertension and congestive heart failure,was used as a model drug.The nanoparticles from three block copolymers with compositions of 5k-7.5k,5k-5k,and 5k-2.5k (PEO-b-PCL) exhibited drug-loading efficiency of 38%,47%.and 26%,respectively,for an equivalent amount of EPM in a 1%(w/v) micelle solution.Particularly,5k-5k micelles could be incorporated with the model drug up to 47% (w/w) of polymer.Furthermore,these nanoparticles possess drug-retaining capability at 25 deg C or below even after free EPM was eliminated from the aqueous phase by dialysis.A temperature-responsive release behavior was displayed upon heating to the physiological temperature,37deg C.Drug release from the micelles proceeded in a fairly linear fashion for a duration of about 4-7 days,depending on the composition of the block copolymers.Daily average fractional release was consistent regrdless of drug contents in the nanoparticles.In a preliminary animal toxicity test the EPM-loaded micelle solutions were intravenously administered to mice of the ICR solution up to six times and showed normal weight gain and food consumption.