Melittin-modified Paclitaxel Liposomes as a Synergistic Strategy for Anti-keloid Therapy

To address the challenges associated with keloid pharmacotherapy, we developed a melittin (MEL)-modified paclitaxel (PTX) liposomal delivery system as a reconstitutable lyophilized formulation intended for subcutaneous injection. MEL, an amphipathic membrane-active peptide, was incorporated as a functional component to enhance liposome-cell interactions and facilitate intracellular delivery of PTX. This design aimed to improve the in vitro anti-keloid activity of PTX liposomes while providing a lyophilized injectable formulation suitable for reconstitution before use. After MEL modification, the zeta potential shifted upward with increasing MEL content, supporting MEL surface modification of PTX liposomes through electrostatic interactions. Moreover, freeze-dried MEL-modified PTX liposomes showed comparable particle size, zeta potential, and release behavior to the original liposomes. Although the encapsulation efficiency (EE%) of PTX and the modification efficiency (ME%) of MEL were slightly reduced after lyophilization, the formulation maintained good storage stability at 4 ± 2°C for 6 months. Confocal microscopy and flow cytometry analyses using coumarin 6 (C6) instead of PTX showed enhanced cellular uptake in human keloid fibroblasts (HKF). The CCK-8 assay indicated that although MEL-Liposome (600:1) alone did not obviously inhibit HKF proliferation under the tested conditions, MEL-PTX-Liposome (600:1) showed significantly stronger antiproliferative activity than PTX-Liposome. Specifically, MEL-PTX-Liposome (600:1) reduced HKF cell migration to 16.8% (control, 92.6%; PTX-Liposome, 36.9%), representing a significant improvement over PTX-Liposome. These findings support MEL-modified PTX liposomes as a promising reconstitutable lyophilized injectable formulation for subcutaneous anti-keloid therapy and provide a formulation basis for further translational development.