A comparative and systematic approach to desolvation and self-assembly methods for synthesis of piperine-loaded human serum albumin nanoparticles

The present work aimed to accomplish a comparative and principled study on desolvation and self-assembly methods for synthesis of piperine-loaded human serum albumin nanoparticles (PIP-HSA-NPs). Among drugs, PIP was selected as the hydrophobic model drug. The response surface methodology (RSM)-central composite design (CCD) was employed to precisely study the processes and the interactions between the factors affecting the methods. Optimization was performed to obtain the best formulations for both procedures. Both optimized PIP-HSA-NPs prepared by the two methods were stable and semi-spherical with the size less than 200 nm. The self-assembled PIP-HSA-NPs which were prepared under the optimized conditions with drug encapsulation efficiency (DEE) of 76.8% +/- 0.44%, and drug loading efficiency (DLE) of 8.92% +/- 0.3% had significantly higher DEE and DLE than the optimized particles obtained from the desolvation method with DEE of 34.1% +/- 0.32% and DLE of 1.68 +/- 0.11%. The secondary structure of HSA did not change much in self-assembled PIP-HSA-NPs compared to desolvated PIP-HSA-NPs. The self-assembled PIP-HSA-NPs showed more cumulative drug release than desolvated NPs, causing them to have more cytotoxicity on MCF-7 cells at high concentrations. These findings introduce the self-assembly technique as the better chemical method to produce a practical cost-effective carrier for many hydrophobic drugs.