Objective To optimize the preparation process of liposomal thermosensitive gel of leech extract and systematically investigate its basic physicochemical properties.

Method The hydrophilic extract of leech was encapsulated into liposomes by the thin-film dispersion method. Using encapsulation efficiency as the evaluation index, the optimal liposome formulation was determined through single-factor experiments combined with orthogonal design. The particle size, polydispersity index (PDI), and zeta potential of the optimized liposomes were characterized, and their storage stability was evaluated. The liposomal thermosensitive gel was then formulated with the optimized liposomes as the drug reservoir; its composition was optimized via single-factor and cross-over experiments, followed by systematic quality evaluation.

Results The optimal formulation for leech extract liposomes was determined to be 40% lecithin concentration, a lecithin-to-cholesterol mass ratio of 4∶1, and a lecithin-to-drug mass ratio of 15∶1. The encapsulation efficiency was 67.37%, drug loading capacity was 5.39%, average particle size was (213.68 ± 7.16) nm, polydispersity index was 0.254 ± 0.02, and zeta potential was (-32.05 ± 0.43) mV. The optimal formulation for the thermosensitive gel containing leech extract liposomes consisted of 18% P407, 10% P188, 3% propylene glycol, and 20% leech extract liposomes. The gelation temperature was (33.1 ± 0.66) °C, and the product was a milky white opaque gel. At room temperature, the viscosity was (184.7 ± 13.4) mPa·s, and when heated to 33.5 °C, the viscosity was (513.9 ± 18.6) mPa·s, with a pH of 4.63 ± 0.04. In in vitro transdermal experiments, the steady-state flux (Jss) of the liposome thermosensitive gel group was 46.12 μg/(cm²·h), which was 1.31 times higher than that of the conventional gel group and 3.68 times higher than that of the free drug group. Comparisons of Jss and cumulative permeation amount over 9 hours showed significant differences among the three groups (P < 0.05), with the liposome-based thermo-sensitive gel group showing significantly higher values than both the conventional gel and free drug groups.

Conclusion The preparation process of leech extract liposomal thermosensitive gel is simple and feasible. The gel rapidly gels upon contact with the skin, covering the scar surface and achieving a long-lasting drug delivery effect.

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