Study of the skin-penetration promoting effect and mechanism of combined system of curcumin liposomes prepared by microfluidic chip and skin penetrating peptides TD-1 for topical treatment of primary melanoma

The transdermal drug delivery system (TDDS) is an effective strategy for the treatment of melanoma with fewer side effects and good biocompatible, but the skin penetration of drugs should be further promoted. Here, we proposed a new system that combined curcumin liposomes (Cur-Lips) with skin-penetrating peptides to promote skin penetration ability. However, the preparation of Cur-Lips has drawbacks of instability and low entrapment efficiency by the traditional methods. We thus innovatively designed and applied a microfluidic chip to optimize the preparation of Cur-Lips. Cur-Lips exhibited a particle size of 106.22 ± 4.94 nm with a low polydispersity index (<0.3) and high entrapment efficiency of 99.33 ± 1.05 %, which were prepared by the microfluidic chip. The Cur-Lips increased the skin penetration capability of Cur by 2.76 times compared to its solution in vitro skin penetration experiment. With the help of skin-penetrating peptide TD-1, the combined system further promoted the skin penetration capability by 4.48 times. The (TD-1 + Cur-Lips) system also exhibited a superior inhibition effect of the tumor to B16F10 in vitro. Furthermore, the topical application of (TD-1 + Cur-Lips) gel suppressed melanoma growth in vivo, and induced tumor cell apoptosis in tumor tissues. The skin-penetration promotion mechanism of the system was investigated. It was proved that the system could interact with the lipids and keratin on the stratum corneum to promote the Cur distribute into the stratum corneum through hair follicles and sweat glands. We proved that the microfluidic chips had unique advantages for the preparation of liposomes. The innovative combined system of liposomes and biological transdermal enhancers can effectively promote the skin penetration effect of drugs and have great potential for the prevention and treatment of melanoma.