HSA nanoparticles in drug recognition: mechanistic insights with naproxen, diclofenac and methimazole.

Protein-based nanoparticles offer a suitable targeted delivery platform to drugs in terms of biocompatibility, biodegradability and abundance in nature. Physicochemical understanding of drug encapsulation by protein nanoparticles and their impact on protein aggregation is essential. In this work, we have examined quantitative aspects of encapsulation of non-steroidal anti-inflammatory drugs naproxen and diclofenac sodium, and anti-thyroid drug methimazole in nanoparticles of human serum albumin (HSA NPs) by using ultrasensitive calorimetry. Thermodynamic signatures accompanying the interactions revealed that the partitioning of all these drugs in HSA NPs is primarily driven via contributions from desolvation of highly hydrated nanoparticles surface. Furthermore, the effect of these nanoparticles on fibrillation of HSA has also been studied. HSA NPs are determined to be ineffective towards inhibition of fibrillation under employed conditions. However, the extent of inhibition by HSA NPs varies depending upon the structural characteristics of the drugs. Such studies help to gain mechanistic aspects on drug loading into protein-based nanoparticles and are expected to provide useful insights into improving existing nano-drug carriers and their efficiency in preventing protein fibrillation.Communicated by Ramaswamy H. Sarma.