Abstract：
Inflammatory skin disorders are the fourth leading cause of chronic non-fatal conditions, which have a serious impact on the patient quality of life. Due to their treatment with conventional corticosteroids, which often result in poor therapeutic efficacy, relapses and systemic side effects from prolonged therapy, these diseases represent a global burden that negatively impacts the global economy. To avoid these problems and optimize corticosteroid benefits, beclomethasone was loaded into liposome formulations specifically tailored for skin delivery. These formulations were enhanced with mucin (0.1 and 0.5 % w/v) to further ensure prolonged formulation permanence at the site of application. The addition of 0.5 % w/v mucin resulted in the formation of small unilamellar vesicles and multicompartment vesicles. Liposomes and 1mucin-liposomes were smaller (∼48 and ∼61 nm, respectively) and more monodispersed (PI ∼ 0.14 and ∼ 0.17, respectively) than 5mucin-liposomes, which were larger (∼137 nm), slightly polydispersed (PI ∼ 0.23), and less stable during storage (4 months in the dark at 25 °C). Liposomes were negatively charged (∼ -79 mV) irrespective of their composition, and capable of incorporating high amount of beclomethasone (∼ 80 %). In vitro studies on skin fibroblasts and keratinocytes confirmed the high biocompatibility of all formulations (viability ≥ 95 %). However, the use of mucin-liposomes resulted in higher efficacy against nitric oxide production and free radical damage. Finally, topical applications using 12-O-tetradecanoylphorbol-13-acetate-injured skin in vivo experiments showed that only the mucin-enriched formulations could restore healthy conditions within 4 days, underscoring promise as a treatment for skin disorders.
摘要：
炎症性皮肤病是慢性非致命疾病的第四大原因，严重影响患者的生活质量。由于他们用常规皮质类固醇治疗，这通常会导致治疗效果不佳，长期治疗的复发和全身副作用，这些疾病代表了对全球经济产生负面影响的全球负担。为了避免这些问题并优化皮质类固醇的益处，倍氯米松被加载到专门为皮肤递送定制的脂质体制剂中。用粘蛋白(0.1%和0.5%w/v)增强这些制剂以进一步确保在施用部位延长的制剂持久性。添加0.5％w/v粘蛋白导致形成小的单层囊泡和多隔室囊泡。脂质体和1粘蛋白-脂质体较小(~48和~61纳米，分别)和比5粘蛋白脂质体更多的单分散(分别为PI〜0.14和〜0.17)，更大的(~137纳米)，略多分散(PI~0.23)，并且在储存期间不太稳定(在25°C黑暗中4个月)。脂质体带负电（〜-79mV），无论其组成如何，并能够掺入大量的倍氯米松(~80%)。对皮肤成纤维细胞和角质形成细胞的体外研究证实了所有制剂的高生物相容性(活力≥95%)。然而,粘蛋白-脂质体的使用导致更高的抗一氧化氮产生和自由基损伤的功效。最后,使用12-O-十四烷酰基佛波醇-13-乙酸酯损伤皮肤的局部应用体内实验表明，只有富含粘蛋白的制剂可以在4天内恢复健康状态，强调作为一种治疗皮肤病的承诺。
