Preparation and characterization of enalapril maleate–loaded nanoparticles using amphiphilic diblock copolymers

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 5 k –7.5 k , 5 k –5 k , and 5 k –2.5 k (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, 5 k –5 k micelles could be incorporated with the model drug up to 47% (w/w) of polymer. Furthermore, these nanoparticles possess drug‐retaining capability at 25°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, 37°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 regardless 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 strain through the tail vein. The animal subjects received 0.7 mL of EPM micelle solution up to six times and showed normal weight gain and food consumption. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 2856–2867, 1999