Design, Development and Characterization of Topical Microemulsions of 5-Fluorouracil for the Treatment of Non Melanoma Skin Cancer and its Precursor Lesions
Design, Development and Characterization of Topical Microemulsions of 5-Fluorouracil for the Treatment of Non Melanoma Skin Cancer and its Precursor Lesions
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DOI：
10.2174/1871520615666150907093551
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发表时间：
2016-01-01
影响因子：
2.8
通讯作者：
Sinha, Vivek Ranjan
中科院分区：
文献类型：
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作者：
Kumar, Sudhir;Sinha, Vivek Ranjan
非黑色素瘤皮肤癌及其癌前皮肤病变的治疗与严重的局部和全身毒性相关。因此，有必要开发一种有效的、副作用小、患者依从性好的新型给药系统。以山梨醇酐单油酸酯（Span 80）、山梨醇酐三油酸酯（Span 85）、聚山梨醇酯80（Tween 80）、异丙醇（IPA）为原料，分别与油酸、三醋精和肉豆蔻酸异丙酯（IPM）等油相混合，制备了5-氟尿嘧啶（5-FU）微乳。进行了微乳的评价试验，如测定热力学稳定性、液滴大小、粘度、pH值、电导率和离体释放研究。透射电子显微镜证实微乳液为球形，液滴大小约为100 nm。与局部5-FU市售乳膏相比，所有微乳液批次的皮肤通量较小，微乳液中装载的5-FU的皮肤保留较高，从而更好地控制药物释放。采用大鼠皮肤刺激性试验，评价优化微乳处方对大鼠皮肤的长期毒性，并与对照组进行比较。以福尔马林（0.8%）为标准刺激物。观察大鼠皮肤的红斑和水肿，发现该制剂长期使用是安全的（p>0.01）。组织学研究显示表皮和真皮层正常，表明5-FU微乳制剂局部使用安全。更好地控制药物通过皮肤的释放可以减少局部和全身毒性，这得到了皮肤刺激和组织病理学研究的支持。
Treatment of non melanoma skin cancer and its precancerous skin lesions is associated with severe topical and systemic toxicity. So, it has become necessary to develop an efficient novel delivery system with less side effects and better patient compliance. Topical w/o microemulsion of 5-FU were prepared using sorbitan monooleate (Span 80), sorbitan trioleate (Span 85), polysorbate 80 (Tween 80), isopropyl alcohol (IPA) with different oils such as oleic acid, triacetin and isopropyl myristate (IPM). Evaluation tests of microemulsions like determination of thermodynamic stability, droplet size, viscosity, pH, conductivity and ex vivo release studies were performed. Spherical shape and Droplet size of microemulsion, which was around 100nm, was supported by Transmission electron microscopy. The lesser flux across skin for all microemulsion batches and higher skin retention of 5-FU loaded in microemulsion in comparison to topical 5-FU marketed cream resulted in better control over the drug release. Skin irritation studies on rats were performed to evaluate chronic toxicity of optimized microemulsion formulation on skin for 21 days and were compared with control group. Formalin (0.8%) was taken as standard irritant. Rat skin was observed for erythema and edema and the formulation was found safe for chronic use (p>0.01). Histopathology studies showed the epidermal and dermal layers to be normal, showing the 5-FU microemulsion formulation to be safe for topical use. Better control of the drug release through skin can curtail topical and systemic toxicity which is supported by the skin irritation and histopathology studies.