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新型载脂蛋白纳米脂质体经皮传递叶黄素治疗银屑病:全面的体外与体内评价。

Novel anti-psoriatic nanostructured lipid carriers for the cutaneous delivery of luteolin: A comprehensive in-vitro and in-vivo evaluation.

机构信息

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University in Egypt, 5th settlement- End of 90th street, Cairo 11245, Egypt.

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University in Egypt, 5th settlement- End of 90th street, Cairo 11245, Egypt.

出版信息

Eur J Pharm Sci. 2023 Dec 1;191:106612. doi: 10.1016/j.ejps.2023.106612. Epub 2023 Oct 15.

Abstract

Psoriasis is a prevalent laborious inflammation in skin with alternate phases of remission and relapses. The current study sought to develop nanostructured lipid carriers (NLCs) having enhanced skin deposition as well as augmented anti-inflammatory potential, to repurpose the use of luteolin (Lut), a flavonoid, in the treatment of psoriasis. NLCs were prepared using different oils having reported anti-inflammatory activity and evaluated in terms of size, surface charge, entrapment efficiency, stability upon storage, in-vitro anti-inflammatory potential, surface morphology, in-vitro release profile and release kinetics, and ex-vivo skin deposition. In-vivo animal studies were conducted on the optimized formula using imiquimod-induced psoriasis rat model. The prepared NLCs were nanosized ranging from 202 to 538 nm, negatively charged with values having the range of -13.10 to -19.26 mV with high entrapment efficiency values ranging from 84.21 to 96.53% and high in-vitro anti-inflammatory potential compared to the blank and control formulations. Furthermore, NLCs demonstrated adequate storage stability demonstrated by slightly significant change in their colloidal properties. The prepared nanoparticles exhibited sustained drug release up to 24 h and succeeded in enhancing the skin deposition of Lut by 3.4-fold higher in stratum corneum, epidermis and dermis compared to Lut suspension with minimum transdermal delivery. In-vivo assessment of psoriasis was carried out morphologically, histopathologically and biochemically and results revealed significant augmentation of the anti-psoriatic efficacy of Lut upon its encapsulation in NLCs compared to free Lut suspension. The developed system proved to be an influential drug delivery system providing potent anti-psoriatic therapy, paving the way for futuristic clinical investigations.

摘要

银屑病是一种常见的皮肤炎症性疾病,具有缓解和复发的交替阶段。本研究旨在开发具有增强皮肤沉积和增强抗炎潜力的纳米结构脂质载体(NLCs),以重新利用黄酮类化合物木犀草素(Lut)治疗银屑病。使用具有报道的抗炎活性的不同油制备 NLCs,并根据粒径、表面电荷、包封效率、储存稳定性、体外抗炎潜力、表面形态、体外释放曲线和释放动力学以及体外皮肤沉积进行评估。使用咪喹莫特诱导的银屑病大鼠模型对优化配方进行了体内动物研究。所制备的 NLCs为纳米级,粒径为 202-538nm,带负电荷,表面电荷值范围为-13.10 至-19.26mV,包封效率值高达 84.21%至 96.53%,体外抗炎潜力高于空白和对照制剂。此外,NLCs 表现出良好的储存稳定性,其胶体性质略有显著变化。所制备的纳米颗粒表现出持续的药物释放,可达 24 小时,并成功将 Lut 的皮肤沉积提高了 3.4 倍,在角质层、表皮和真皮中均高于 Lut 混悬液,且经皮传递最小。通过形态学、组织病理学和生物化学进行了银屑病的体内评估,结果表明,与游离 Lut 混悬液相比,Lut 包封在 NLCs 中显著提高了其抗银屑病疗效。所开发的系统被证明是一种有效的药物传递系统,提供了有效的抗银屑病治疗,为未来的临床研究铺平了道路。

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