以质量为导向设计开发用于皮肤靶向的脂质纳米颗粒:一种初步方法。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-08-15 DOI:10.1007/s13346-024-01685-9
Viral Patel, Tejal Mehta, Jigna Shah, Kinal Soni
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引用次数: 0

摘要

真菌感染是第四大常见感染病因,影响着全球约 5000 万人口。大多数表皮真菌感染都是由皮癣菌引起的。克霉唑(CTZ)是一种咪唑类衍生物,是治疗局部真菌感染的首选药物。传统的外用制剂能使 CTZ 有效渗透到角质层,但其溶解度低,导致皮肤生物利用度差,而且药物浓度不一,限制了疗效。我们的目标是提高皮肤生物利用度和药物持续释放,从而提高药物保留率并减少副作用。这项研究评估了由 Precirol 和聚山梨醇酯-80 组成的 CTZ 负载固体脂质纳米颗粒(SLN),该颗粒采用高压均质法开发,并通过 QbD 方法进行了优化。在进行释放研究之前,采用不同的分析技术对 CTZ-SLN 进行了表征。激光衍射仪和场发射扫描电子显微镜显示,SLNs 呈球形,平均直径为 450 ± 3.45 nm。DSC 和 XRD 结果表明,药物在脂质基质中保持分子分散状态。CTZ-SLNs 在不同温度下贮存 6 个月期间未显示出理化不稳定性。此外,具有假塑性行为的 Carbopol 在形成均匀稳定的网络以浸润 CTZ-SLN 分散体从而有效保留在皮肤中方面发挥了关键作用。经检测,体外药物释放可持续24小时,而体外皮肤保留和药物渗透研究表明,与纯药物和Candid®乳膏相比,纳米凝胶的蓄积量最高,渗透率最低。此外,纳米凝胶的体内抗真菌疗效表明,每天使用一次,可持续 10 天,组织病理学分析证明可完全根除感染。总之,研究结果表明,负载 CTZ-SLNs 的纳米凝胶在治疗由白色念珠菌引起的真菌感染方面具有巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Quality by design driven development of lipid nanoparticles for cutaneous targeting: a preliminary approach.

Quality by design driven development of lipid nanoparticles for cutaneous targeting: a preliminary approach.

Fungal infections are the fourth common cause of infection affecting around 50 million populations across the globe. Dermatophytes contribute to the majority of superficial fungal infections. Clotrimazole (CTZ), an imidazole derivative is widely preferred for the treatment of topical fungal infections. Conventional topical formulations enable effective penetration of CTZ into the stratum corneum, however, its low solubility results in poor dermal bioavailability, and variable drug levels limit the efficacy. The aim was to increase dermal bioavailability and sustain drug release, thereby potentially enhancing drug retention and reducing its side effects. This work evaluated the CTZ loaded solid lipid nanoparticles (SLN) consisting of precirol and polysorbate-80 developed using high pressure homogenization and optimized with QbD approach. Prior to release studies, CTZ-SLNs were characterized by different analytical techniques. The laser diffractometry and field emission scanning electron microscopy indicated that SLNs were spherical in shape with mean diameter of 450 ± 3.45 nm. DSC and XRD results revealed that the drug remained molecularly dispersed in the lipid matrix. The CTZ-SLNs showed no physicochemical instability during 6 months of storage at different temperatures. Further, the Carbopol with its pseudoplastic behavior showed a crucial role in forming homogenous and stable network for imbibing the CTZ-SLN dispersion for effective retention in skin. As examined, in-vitro drug release was sustained up to 24 h while ex-vivo skin retention and drug permeation studies showed the highest accumulation and lowest permeation with nanogel in comparison to pure drug and Candid® cream. Further, the in-vivo antifungal efficacy of nanogel suggested once-a-day application for 10 days, supported by histopathological analysis for complete eradication infection. In summary, the findings suggest, that nanogel-loaded with CTZ-SLNs has great potential for the management of fungal infections caused by Candida albicans.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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