Enhancing efficacy of combretastatin A4 by encapsulation in solid lipid nanoparticles: Implications for...

Nanotechnology-based drug delivery systems, such as solid lipid nanoparticles (SLNs), offer promising strategies to enhance the efficacy and stability of therapeutic agents. In this study, we explored the characterization, stability, and therapeutic efficacy of SLNs loaded with Combretastatin A4 (CA4) in cancer treatment.

SLNs loaded with CA4 were characterized for particle size, zeta potential, and encapsulation efficiency. The stability of CA4 SLNs was assessed over six months. The MTT assay was used to evaluate the cytotoxicity of free CA4 and SLNs loaded with CA4 on C26 mouse colon carcinoma cells and HUVEC human umbilical vein endothelial cells. The anti-angiogenic activity was analyzed using the CAM assay. An in vivo study was conducted to assess the therapeutic efficacy of SLNs loaded with CA4 in combination with Doxil in a mouse tumor model.

Blank SLNs and SLNs loaded with CA4 exhibited a homogeneous particle size distribution (60-70 nm and 80-90 nm, respectively), low polydispersity index, and a negative zeta potential. Encapsulation efficiency of CA4 was around 60 %. SLNs demonstrated excellent physicochemical stability over six months. The MTT assay revealed enhanced cytotoxicity of SLNs loaded with CA4 compared to free CA4, particularly in C26 cells. The CAM assay showed a concentration-dependent reduction in vessel density with CA4 treatment. In in vivo studies, SLNs loaded with CA4 significantly inhibited tumor growth and improved survival rates, especially when combined with Doxil.

These findings suggest that SLNs loaded with CA4 could be a valuable strategy for enhancing therapeutic outcomes in cancer treatment.