Objective: In order to improve patient compliance and the ease of use during progesterone application, and to increase the clinical application of progesterone, progesterone was made into a microneedle. Methods: Progesterone complexes were prepared using a single-factor and central composite design. In the preparation of the microneedles, the tip loading rate was used as an evaluation index. The selection of tip materials among the biocompatible materials of gelatin (GEL), hyaluronic acid (HA), and polyvinylpyrrolidone (PVP), and the use of polyvinyl alcohol (PVA) and hydroxypropyl cellulose (HPC) as backing layers, respectively, were carried out and the resulting microneedles were evaluated accordingly. Results: The progesterone inclusion complexes prepared at a molar ratio of 1:2.16 progesterone and hydroxypropyl-β-cyclodextrin (HP-β-CD), a temperature of 50 °C, and reaction time of 4 h had high encapsulation and drug-loading capacities of 93.49% and 9.55%, respectively. Gelatine was finally chosen as the material for the preparation of the micro-needle tip based on the drug loading rate of the tip. Two types of microneedles were prepared: one with 7.5% GEL as the tip and 50% PVA as the backing layer, and one with 15% GEL as the tip and 5% HPC as the backing layer. The microneedles of both prescriptions exhibited good mechanical strength and penetrated the skin of rats. The needle tip loading rates were 49.13% for the 7.5% GEL-50% PVA microneedles and 29.31% for the 15% GEL-5% HPC microneedles. In addition, in vitro release and transdermal experiments were performed using both types of microneedles. Conclusion: The microneedles prepared in this study enhanced the in vitro transdermal amount of progesterone drug by releasing the drug from the microneedle tip into the subepidermis.

Objectives: To fabricate polysialic acid (PSA)-modified liposomes co-loaded with doxorubicin (DOX) and indocyanine green (ICG) for synergistic chemotherapy and photothermal therapy, and to enhance the anti-cervical cancer efficacy of liposomes via neutrophil targeting. Methods: PSA-DOX/ICG liposomes (PSA-DOX/ICG-Lip) were prepared by microfluidic technology. The physicochemical properties, including drug encapsulation efficiency (EE), loading capacity (LC), particle size, polydispersity index (PDI), zeta potential, and stability, were systematically characterized. The in vitro anti-tumor activity was evaluated using cellular uptake, apoptosis assays, reactive oxygen species (ROS) detection, and a cell scratch test in HeLa and C33a cells. The in vivo therapeutic efficacy was verified using a nude mouse xenograft model of cervical cancer combined with histopathological analysis. Results: Microfluidic preparation yielded PSA-DOX/ICG-Lip with favorable physicochemical properties: the EE and LC of DOX were 96.52 ± 0.43% and 8.70 ± 0.04%, respectively, while those of ICG were 90.72 ± 1.10% and 0.82 ± 0.02%. The average particle size was 92.68 ± 1.14 nm with a PDI of 0.04 and a zeta potential of −9.66 ± 0.46 mV. The liposomes maintained good stability in terms of EE, particle size, PDI, and zeta potential after 28 days of storage at 4 °C and room temperature, with PSA modification significantly reducing the drug leakage rate. In vitro drug release studies showed that 808 nm laser irradiation triggered a significant increase in drug release from the liposomes. ICG encapsulated in liposomes mediated localized photothermal heating, and PSA targeting precisely confined the therapeutic effect to the tumor site, minimizing damage to adjacent normal tissues. In vitro experiments demonstrated that PSA-DOX/ICG-Lip, combined with laser irradiation, significantly enhanced cellular uptake, elevated intracellular ROS levels, inhibited cancer cell migration, and induced apoptosis. In vivo studies confirmed that this formulation markedly suppressed tumor growth in nude mice, with a tumor inhibition rate of 81.5%, and exhibited good biocompatibility without obvious organ toxicity. Conclusions: The microfluidically prepared PSA-DOX/ICG-Lip possesses high drug encapsulation efficiency, uniform particle size, good stability and sustained drug release properties. It can efficiently convert light energy into thermal energy, target neutrophils to enhance the affinity for cervical cancer cells, and exert a synergistic anti-tumor effect via the combination of chemotherapy and photothermal therapy, which provides a promising nanoplatform for the precise treatment of cervical cancer.