Direct formation of nanospheres from amphiphilic beta-cyclodextrin inclusion complexes

The aim of this work was to develop and characterize a highly loaded nanoparticulate system based on amphiphilic beta-cyclodextrins (CDs) to facilitate the parenteral administration of poorly soluble antifungal model drugs bifonazole and clotrimazole.

Inclusion complexes were characterized with spectroscopic techniques. Particle size distribution of nanospheres were determined by photon correlation spectroscopy (PCS). Nanospheres were assessed for hemolytic activity. Entrapped and released drug quantities were determined and minimum inhibitory concentration (MIC) values of drugs, amphiphilic beta-CDs, and drug loaded nanospheres were evaluated.

1:1 inclusion complexes of model drugs with amphiphilic beta-CDs gave nanospheres <300 nm (polydispersity index < 0.15) by nanoprecipitation technique without using surfactants. By direct preparation from preformed inclusion complexes, loading was increased 2- to 8-fold depending on CD type and loading technique. Conventionally loaded CD nanospheres displayed immediate release whereas preloaded and highly loaded nanospheres liberated model drugs over a period of 1 h reducing the initial burst effect. MIC values of bifonazole and clotrimazole were lowered significantly when associated to amphiphilic beta-CD nanospheres.

Amphiphilic beta-CDs form nonsurfactant, highly loaded nanospheres with lower hemolytic activity than that of natural CDs directly from inclusion complexes. They enhanced solubility and subsequently therapeutic efficacy of the model drugs.