Preparation and evaluation of in-vitro release of amphiphilic β-cyclodextrin or PLA nanospheres containing a hydrophobic drug

摘要

Mebendazole (MBZ) is an antihelmintic which belongs the benzimidazols. It is used against many intestinal diseases, and can also be efficient against extra-intestinal diseases MBZ has poor oral bioavailability resultives from its insolubility and its extensive first pass metabolism in the liver In the present work several formulations of amphiphilic P-cyclodextrin (P-CD-C6 and P-CD-C12) and poly(lactic acid) (PLA) nanospheres containing mebendazole (MBZ) were prepared according to the nanospherical cristallization and the nanoprecipitation techniques. These formulation differed in the type of polymer used to form the core of the nanospheres. Analysis of particle size distribution and encapsulation efficiency of the nanospheres revealed that the type and molecular weight of amphiphilic (3-cyclodextrin used were the main factor influencing these properties, p-CD-C12 had the highest encapsulation efficiency with the best reproducibility From in-vitro release studies, a small amount of MBZ release was observed at pH 10 However, in gastric medium, an important burst effect occurred and was highest with P-CD-C6 and PLA and lowest with P-CD-C12, suggesting that drag release from these systems is affected by the type of cyclodextrins and the environnemental conditions. The two formulations of MBZ-loaded nanospheres should be evaluated based on p-CD-Q , P-CD-Cn and PLA in-vivo in order to determine to what extent they are able to reduce the local side effects of this drug.