Fabrication and Evaluation of Cassava Starch Acetate Nanoparticles Loaded with Drugs of Various BCS Classes: Influence of Drug Solubility and Partition Coefficient

Abstract

A successful fabrication of nanocarrier for drug delivery should yield nanoparticles (NPs) with suitable particle size and size distribution and provide high drug-loading capacity. Factors that influence these attributes include physicochemical properties of the drug, the nature of the nanocarrier, and processing variables, among others. The aim of this study was, therefore, to investigate the influence of solubility and partition coefficient of different drugs on the characteristics of starch-based NPs. Cassava starch was chemically modified by acetylation, at different degrees of substitution (DS) and characterized. The starch acetates (SAs) were then used for the preparation of drug-loaded NPs. Different model drugs: ibuprofen (BCS class II), acyclovir (BCS class III) and furosemide (BCS class IV) were incorporated into NPs using emulsification solvent evaporation technique. The effects of solubility and partition coefficient, and DS of SA on the properties of NPs, namely, size and size distribution, drug loading capacity (DL), encapsulation efficiency (EE) and in vitro release profile were investigated. The results showed that the DL and EE of ibuprofen and furosemide loaded starch acetate nanoparticles (SANPs) increased consistently with an increase in the DS of SA. On the contrary, DL and EE of acyclovir-loaded NPs decreased as DS of SA increased. Due to their poor solubility and high partition coefficient, the EEs of ibuprofen and furosemide in SANPs fabricated from SA with high DS were much greater than that of acyclovir. Furthermore, as DS of SA increased the cumulative release profile of Ibuprofen from SANPs was retarded whereas the release profile of acyclovir was enhanced. On the other hand, furosemide, the most lipophilic drug of all, exhibited lowest release profile over the study period of 8 h. In conclusion, along with the hydrophobic nature of SA, the DL, EE and drug release profile from SANPs depended on the solubility and partition coefficient of the incorporated drug molecule.