Dubey Prashant, Kumar Ankaj, Vaiphei Klaudi K, Basrani Sargun, Jadhav Ashwini, Wilen Carl-Eric, Rosenholm Jessica M, Bansal Kuldeep K, Chakravarti Rudra, Ghosh Dipanjan, Gulbake Arvind
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Guwahati Assam 781101 India
Department of Medical Biotechnology, CIR, D.Y. Patil Education Society, Institution Deemed to be University Kolhapur India.
Nanoscale Adv. 2024 Aug 2;6(21):5322-36. doi: 10.1039/d4na00176a.
This study aimed to investigate the potential of poly-δ-decalactone (PDL) and a block copolymer (methoxy-poly(ethylene glycol)--poly-δ-decalactone (mPEG--PDL)) in the topical delivery of ketoconazole (KTZ) and eugenol (EUG) against . The nanoemulsion (NE) was studied for its significant factors and was optimized using the design of experiments (DOE) methodologies. A simple robust nanoprecipitation method was employed to successfully produce a nanoemulsion (KTZ-EUG-NE). The spherical globules exhibited rough surfaces, explaining the adsorption of mPEG--PDL onto PDL. The sustained drug release effects were governed by the amorphous nature of PDL. KTZ-EUG-NE was further used to develop a 1% w/v Carbopol-940-based nanoemulgel (KTZ-EUG-NE gel). The optimal rheological and spreadability properties of the developed nanoemulgel explain the ease of topical applications. permeation and retention studies confirmed the accumulation of KTZ-EUG-NE at different layers of the skin when applied topically. The cytotoxicity of the developed NE in human keratinocyte (HaCaT) cells demonstrated the utility of this newly explored nanocarrier in reducing the cell toxicity of KTZ. The higher antifungal activities of KTZ-EUG-NE at 19.23-fold lower concentrations for planktonic growth and 4-fold lower concentrations for biofilm formation than coarse drugs explain the effectiveness of the developed NE.
本研究旨在探究聚 -δ- 癸内酯（PDL）和一种嵌段共聚物（甲氧基聚（乙二醇）- 聚 -δ- 癸内酯（mPEG - PDL））在酮康唑（KTZ）和丁香酚（EUG）局部给药中的潜力。对纳米乳剂（NE）的显著因素进行了研究，并使用实验设计（DOE）方法进行了优化。采用一种简单可靠的纳米沉淀法成功制备了纳米乳剂（KTZ - EUG - NE）。球形颗粒表面粗糙，这解释了 mPEG - PDL 在 PDL 上的吸附现象。药物的持续释放效果受 PDL 无定形性质的控制。KTZ - EUG - NE 进一步用于制备基于 1% w/v 卡波姆 - 940 的纳米乳凝胶（KTZ - EUG - NE 凝胶）。所制备的纳米乳凝胶具有最佳的流变学和铺展性，这解释了其易于局部应用的原因。渗透和滞留研究证实，局部应用时 KTZ - EUG - NE 在皮肤的不同层中积累。所制备的 NE 对人角质形成细胞（HaCaT）的细胞毒性表明，这种新探索的纳米载体在降低 KTZ 的细胞毒性方面具有实用性。与粗药物相比，KTZ - EUG - NE 在浮游生长时浓度低 19.23 倍、生物膜形成时浓度低 4 倍的情况下具有更高的抗真菌活性，这解释了所制备的 NE 的有效性。
