Ghalwash Maha M, Fouad Amr Gamal, Mohammed Nada H, Nagib Marwa M, Khalil Sherif Faysal Abdelfattah, Belal Amany, Miski Samar F, Albezrah Nisreen Khalid Aref, Elsayed Amani, Hassan Ahmed H E, Roh Eun Joo, El-Housiny Shaimaa
Department of Pharmaceutics and Drug Manufacturing, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11435, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
Pharmaceuticals (Basel). 2024 Dec 30;18(1):31. doi: 10.3390/ph18010031.
BACKGROUND/OBJECTIVES: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB's low solubility, poor bioavailability, resistance, poor targeting, and first-pass action make it less effective when taken orally. This investigation set out to design an intratumoral in situ pH-sensitive hydrogel of SDB-invasomes (IPHS-INV) that can effectively treat BCSC by improving SDB's bioavailability, sustainability, targeting, and efficacy while also reducing its resistance and undesirable side effects.
Numerous S-INV formulations were developed using Box-Behnken Design Expert and tested before settling on the optimum S-INV formulation. An experimental 7, 12-dimethylbenzanthracene (DMBA) carcinoma rat model was used for in vivo studies of the IPHS-INV formulation after it was combined with chitosan.
Phospholipids (1.72% /), cholesterol (0.15% /), ethanol (1% /), and cineole (1.5% /) were shown to be the optimal components in the SDB-invasome formulation. The IPHS-INV formulation outperformed the permeation and bioavailability of free SDB by 7.14 and 6 times, respectively, and sustained its release by 57.41%. The IPHS-INV formulation showed a decrease in tumor volume of 99.05% and a reduction of hypercellular tumors, indicating its anti-cancer activity. The intratumoral IPHS-INV formulation maintained a higher concentration of SDB in tumors, indicating its targeting activity.
These findings support the use of the intratumoral IPHS-INV formulation as an effective strategy for the treatment of BCSC.
背景/目的：当皮肤细胞不受控制地增殖时，就会发生基底细胞皮肤癌（BCSC）。索尼德吉（SDB）是一种通过抑制刺猬信号通路来治疗BCSC的治疗选择。SDB存在溶解度低、生物利用度差、耐药性、靶向性差和首过效应等问题，口服时效果较差。本研究旨在设计一种SDB侵袭体瘤内原位pH敏感水凝胶（IPHS-INV），通过提高SDB的生物利用度、可持续性、靶向性和疗效，同时降低其耐药性和不良副作用，来有效治疗BCSC。
使用Box-Behnken Design Expert开发了多种S-INV制剂，并在确定最佳S-INV制剂之前进行了测试。将IPHS-INV制剂与壳聚糖结合后，使用实验性7,12-二甲基苯并蒽（DMBA）癌大鼠模型进行体内研究。
磷脂（1.72%/）、胆固醇（0.15%/）、乙醇（1%/）和桉叶油素（1.5%/）被证明是SDB侵袭体制剂中的最佳成分。IPHS-INV制剂的渗透和生物利用度分别比游离SDB高7.14倍和6倍，其释放持续时间为57.41%。IPHS-INV制剂显示肿瘤体积减少了99.05%，高细胞肿瘤减少，表明其抗癌活性。瘤内IPHS-INV制剂在肿瘤中保持较高浓度的SDB，表明其靶向活性。
这些发现支持将瘤内IPHS-INV制剂用作治疗BCSC的有效策略。
