Nanoparticle assisted solvent selective transdermal combination therapy of curcumin and 5-flurouracil for efficient cancer treatment.

Skin cancer is one among the many prominent diseases of the modern world and millions of people are suffering due to the lack of proper medication. Even though transdermal drug delivery systems (TDDS) provide an efficient route of drug administration, the advantages of combination chemotherapy have rarely been extended into TDDS. In the present work, a polymer capable of simultaneously encapsulating two anti-cancer drugs: 5-flurouracil (5-FU) and curcumin (CUR), and releasing them with varying kinetics as a function of the leaching solvent was developed. The prepared TDDS had two copolymers: alginate coated aminated nanodextran (ALG@AND) and chitosan coated folate decorated aminated β-CD nano particles (CS@FA-g-AβCD). After inducing surface charges, both copolymers were coupled together by electrostatic forces. All the synthetic procedures for the preparation of TDDS were monitored using FTIR, DLS, Zeta Potential, SEM and TEM. The final TDDS was then evaluated for its solvent selectivity. Sustained release of 5-FU and CUR was observed with ethanol (EtOH) and 1-butanol (BuOH) respectively. However, these solvents could also release a small amount of the second drug which led to combinatorial therapy. The in vitro solvent selective drug permeation profiles were evaluated using Franz diffusion cell on rat skin. In order to evaluate the economic feasibility of the prepared TDDS, in vivo skin adhesion tests, skin irritation analysis, water vapour permeability and average visible transmittance were performed. Results proved that solvents could not only elute the drugs in a sustained manner, but could also act as penetration enhancers. Biological and histological studies carried out on skin and cancer cell lines suggested the potential usefulness of the prepared material in combinatorial chemotherapy.