Enhancing Olaparib's anti-cancer potential using nanostructured lipid carriers: formulation, evaluation, and in-vitro...

Area of Science:

• Nanotechnology
• Pharmaceutics
• Oncology

Background:

• Triple Negative Breast Cancer (TNBC) presents a significant therapeutic challenge.
• Olaparib (OLA) is a PARP inhibitor with potential against TNBC, but its delivery requires optimization.
• Nanostructured lipid carriers (NLCs) offer a promising platform for improving drug delivery and efficacy.

Purpose of the Study:

• To design and optimize olaparib-loaded nanostructured lipid carriers (OLA-NLCs).
• To evaluate the physicochemical properties, drug release kinetics, and in vitro efficacy of OLA-NLCs against TNBC.
• To investigate the potential of NLCs for enhancing olaparib's therapeutic effect in TNBC.

Main Methods:

• Formulation of OLA-NLCs using melt emulsification and ultrasonication.
• Optimization of NLC formulation using a Box-Behnken design (DoE).
• Characterization of NLCs for particle size, polydispersity index, zeta potential, entrapment efficiency, and drug loading.
• In vitro drug release studies over 72 hours.
• Assessment of OLA-NLC efficacy using MDA-MB-231 (TNBC) cell lines.

Main Results:

• Optimized OLA-NLCs exhibited favorable physicochemical properties: particle size (126.0 nm), PDI (0.2), zeta potential (-13.6 mV), entrapment efficiency (88.5%), and drug loading (14.8%).
• The OLA-NLC system demonstrated sustained drug release, with 84.49% cumulative release over 72 hours, significantly longer than unformulated OLA (24 hours).
• OLA-NLCs showed significantly greater efficacy against MDA-MB-231 TNBC cells compared to plain OLA (p < 0.05).

Conclusions:

• Nanostructured lipid carriers provide a viable and effective delivery system for olaparib in TNBC treatment.
• The optimized OLA-NLC formulation enhances olaparib's therapeutic efficacy through sustained release and improved cellular activity.
• NLCs hold substantial promise for advancing the treatment of Triple Negative Breast Cancer.