Overcoming cordycepin limitations with SLNs-based nanoformulation: formulation development and cytotoxicity...

Problems of low bioavailability, rapid systemic degradation, non-selective targeting, and high toxicity often mar conventional cancer therapies. Cordycepin (COR), a natural adenosine analogue with potent anticancer activity, particularly against breast cancer, is limited by its high rate of inactivation through the enzyme adenosine deaminase, instability at stomach pH, and poor pharmacokinetics, thus reducing its therapeutic potential. To address these limitations, we have designed a solid lipid nanoparticles (SLNs)-based delivery system for the effective entrapment and release of COR to improve its stability, cellular uptake, and cytotoxic efficacy against MCF-7 human breast cancer cells. The synthesized COR-loaded SLNs (CSLN) were found to be monodispersed, spherical nanoparticles with good physical and chemical stability. In vitro release studies exhibited sustained release behaviour in acidic and physiological conditions, mimicking the endo-lysosomal and systemic circulation pH, respectively. The results of cytotoxicity assays indicated that CSLN significantly enhanced the cytotoxic efficacy of COR against MCF-7 cells as contrasted to the free drug. Improved cellular uptake and greater drug accumulation inside cells led to improved apoptotic activity and thus, more clonogenic activity. These findings suggest that SLNs-based nanoencapsulation is a promising approach for enhancing the therapeutic efficacy and safety of COR for breast cancer therapy.