Development and Evaluation of a PH-Responsive Bovine Serum Albumin-Functionalized Layered Double Hydroxide Nanocarrier for Targeted Therapy of Ovarian Cancer

Abstract

Purpose: Ovarian cancer accounts for 4.7% of cancer-related deaths in women, with paclitaxel (PAC) being an effective treatment option. However, poor water solubility and inefficient release within the tumor microenvironment limit its clinical use. This study aims to optimize a novel PAC pH-sensitive nanocarrier system based on layered double hydroxide (LDH) functionalized with bovine serum albumin (BSA) to enhance its delivery and release.

Methods: A response surface D-optimal design was utilized to optimize the formulation of BSA-d-LDH-PAC nanoparticles, considering particle size (PS), drug entrapment efficiency (EE%), and zeta potential (ZP). The optimized formulation (F3) was characterized using structural and physicochemical analyses, and in vitro drug release studies were conducted at different pH levels. Additionally, cytotoxicity studies were performed to evaluate the therapeutic potential of the developed system.

Results: The optimized formulation (F3) incorporated 16 mg/mL BSA, 0.5 mg PAC, and delaminated layered double hydroxide (d-LDH), yielding nanoparticles with a brucite-like structure, a diameter of 95 nm, a ZP of -27 mV, and an EE% of 51%. Molecular modeling and FTIR analysis confirmed the layered LDH structure and successful integration of BSA and PAC via hydrogen bonding, contributing to high drug loading and entrapment efficiency. The less ordered particle arrangement enhanced PAC aqueous solubility and facilitated rapid release, with 90% of the drug released at pH 5.5 within 5 h. Cytotoxicity studies demonstrated the superior anticancer activity of BSA-d-LDH-PAC compared to free PAC suspension.

Conclusion: BSA-functionalized LDH nanoparticles provide an efficient, pH-responsive delivery system for PAC, improving solubility, controlled release, and cytotoxic efficacy. These findings emphasize the future promise of this nanocarrier system for enhanced ovarian cancer treatment and broader applications in targeted drug delivery.