Co-delivery of SN38 and rapamycin albumin bound nanoparticles against breast Cancer

The co-delivery of two therapeutic agents within a single nanoparticle platform offers a potential strategy to improve treatment efficacy while minimizing adverse effects. Albumin as a biocompatible carrier could facilitate simultaneous delivery of cargos to the tumoral region based on passive targeting gained by enhanced permeability and retention (EPR).

This study aimed to develop, characterize, and assess a dual-drug delivery system incorporating rapamycin and SN38, utilizing the nanoparticle albumin bound technique, for the treatment of breast cancer.

Albumin bound NPs of SN38 and rapamycin were prepared using probe sonication method. NPs were characterized using dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) techniques to confirm their hydrodynamic diameter and structural properties. Drug loading (DL) and entrapment efficiency (EE) were measured using validated reverse phase high performance liquid chromatography (RP-HPLC) methods. Cellular cytotoxicity assay, cellular internalization, quantitatively cellular uptake, colony formation assay, and sphere formation assay were performed. To track NPs destiny as a 24 h follow up in the biodistribution part, NPs were intravenously injected to the BALB/c tumor bearing mice.

Blank NPs showed hydrodynamic diameter of about 121 nm, drug incorporation resulted in sizes around 200 nm. No toxicity was observed by MTT assay for blank albumin NPs. MTT assay of drug loaded NPs showed higher toxicity for dual drug loaded NPs compared to single drug loaded NPs. Confocal images and flow cytometry showed high accumulation of NPs in cytoplasmic space of 4T1 cells. All of the experimental groups showed significant decrease in colony formation and sphere formation in comparison to the control group. NPs were also preferentially accumulated in the tumoral region in vivo due to their suitable size.

In conclusion, the designed drug delivery system proposes great potential for breast cancer treatment.