In silico and experimental studies of bovine serum albumin-encapsulated carbenoxolone nanoparticles with reduced cytotoxicity.

Bharathala, Subhashini; Kotarkonda, Lakshmi Kanth; Singh, Vijay Pal; Singh, Rajni; Sharma, Pankaj

Carbenoxolone (CBX) is a semi-synthetic plant derivative with pleiotropic pharmacological properties like anti-microbial and anti-inflammatory activities. Though approved for treatment of gastric ulcers, its use is limited due to adverse effects such as cytotoxicity. Bovine serum albumin (BSA) is a natural, non-toxic protein with high water-solubility and low immunogenicity, and is widely used as a nanocarrier for targeted drug delivery. In the present study, controlled release BSA-CBX nanoparticles (NPs) were synthesized by desolvation method to reduce drug cytotoxicity. These NPs showed desirable physicochemical properties such as particle size (∼240 nm), polydispersity index (0.08), zeta potential (-7.12 mV), drug encapsulation efficiency (72 %), and were stable for at least 3 months at room temperature. The drug was released from the BSA-CBX NPs in a biphasic manner in vitro following non-fickian diffusion. Computational analysis determined that the binding between BSA and CBX occurred through van der Waals forces, hydrophobic interactions, and hydrogen bonds with 93 % steric stability. Further, the cytotoxic assays demonstrated ∼1.8-4.9-fold reduction in cytotoxicity using three human cell lines (A549, MCF-7, and U-87). Subsequently, this novel CBX formulation with BSA as an efficient carrier can potentially be used for diverse biomedical applications.