设计质量认可的负载阿托伐他汀的纳米结构脂质载体嵌入用于黑色素瘤的pH响应凝胶中。
Quality by design endorsed atorvastatin-loaded nanostructured lipid carriers embedded in pH-responsive gel for melanoma.
作者信息
Bagasariya Deepkumar, Charankumar Kondasingh, Shah Saurabh, Famta Paras, Fernandes Valencia, Shahrukh Syed, Khatri Dharmendra Kumar, Singh Shashi Bala, Srivastava Saurabh
机构信息
Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
出版信息
J Microencapsul. 2024 Jan;41(1):27-44. doi: 10.1080/02652048.2023.2282971. Epub 2024 Jan 10.
AIM
Our aim was to repurpose atorvastatin for melanoma by encapsulating in a nanostructured lipid carrier matrix to promote tumour cell internalisation and skin permeation. pH-responsive chitosan gel was employed to restrict At-NLCs in upper dermal layers.
METHODS
We utilised a quality by design approach for encapsulating At within the NLC matrix. Further, cellular uptake and cytotoxicity was evaluated along with pH-responsive release and ex vivo skin permeation.
RESULTS
Cytotoxicity assay showed 3.13-fold enhanced cytotoxicity on melanoma cells compared to plain drug with nuclear staining showing apoptotic markers. release studies showed 5.9-fold rapid release in chitosan gel matrix at pH 5.5 compared to neutral pH.
CONCLUSIONS
At-NLCs prevented precipitation, promoted skin permeation, and SK-MEL 28 cell internalisation. The localisation of NLCs on the upper dermal layer due to electrostatic interactions of skin with chitosan gel diminished the incidence of untoward systemic effects.
目的
我们的目的是通过将阿托伐他汀包裹在纳米结构脂质载体基质中，促进肿瘤细胞内化和皮肤渗透，从而将其用于黑色素瘤治疗。采用pH响应性壳聚糖凝胶将阿托伐他汀纳米脂质载体（At-NLCs）限制在上层真皮层。
方法
我们采用质量源于设计的方法将阿托伐他汀包裹在纳米脂质载体基质中。此外，还评估了细胞摄取和细胞毒性，以及pH响应性释放和离体皮肤渗透情况。
结果
细胞毒性试验显示，与普通药物相比，对黑色素瘤细胞的细胞毒性增强了3.13倍，细胞核染色显示有凋亡标记物。释放研究表明，与中性pH值相比，在pH 5.5的壳聚糖凝胶基质中释放速度快5.9倍。
结论
阿托伐他汀纳米脂质载体可防止沉淀，促进皮肤渗透和SK-MEL 28细胞内化。由于皮肤与壳聚糖凝胶的静电相互作用，纳米脂质载体在上层真皮层的定位减少了不良全身效应的发生。
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