Nanostructured Lipid Carrier-Based Gel for Repurposing Simvastatin in Localized Treatment of Breast Cancer:...

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Oncology

Background:

• Simvastatin (SMV) shows potential for breast cancer (BC) treatment but faces challenges due to poor solubility and toxicity.
• Localized delivery of SMV is crucial to overcome these limitations and improve patient compliance.

Purpose of the Study:

• To develop and characterize simvastatin-loaded nanostructured lipid carriers (NLCs) formulated into a carbopol-934 gel for localized breast cancer therapy.
• To evaluate the physicochemical properties, drug release, permeation, cytotoxicity, and stability of the SMV NLC-based gel.

Main Methods:

• SMV-loaded NLCs were fabricated using stearic acid, olive oil, tween 20, and PEG-200 via melt-emulsification ultrasonication.
• Formulation optimization was performed using Box-Behnken design.
• Characterization included particle size, entrapment efficiency, pH, viscosity, drug release, ex vivo permeation, in vitro cytotoxicity, and in vivo skin irritation studies.

Main Results:

• Optimized SMV NLCs achieved high entrapment efficiency (91.66%) and suitable particle size (182 nm).
• NLC-based gels exhibited controlled SMV release (up to 84%) and significantly enhanced ex vivo permeation (3.8-4.5 times higher than conventional gel).
• SMV-loaded NLCs showed improved cytotoxicity against BC cells, and the NLC gel was found to be safe with no skin irritation in vivo and stable for 6 months.

Conclusions:

• The developed SMV NLC-based gel offers a promising, safe, and effective topical delivery system for breast cancer treatment.
• This nanocarrier approach overcomes SMV's limitations, enhancing its therapeutic potential and patient compliance.