Development and evaluation of imiquimod-loaded nanoemulsion-based gel for the treatment of skin cancer

IF 3.4 Q2 PHARMACOLOGY & PHARMACY Future Journal of Pharmaceutical Sciences Pub Date : 2024-07-29 DOI:10.1186/s43094-024-00660-y

Shital T. Jadhav, Vijay R. Salunkhe, Somnath D. Bhinge, Sandip M. Honmane, Aasha S. Jadhav

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Abstract

Background

The human skin, as the body’s largest organ, is particularly sensitive to many chemical mutagens and carcinogens encountered in daily life. Skin cancer has become a notable global health concern, partly due to increased exposure to environmental pollutants and UV rays. Various treatments are available to treat skin cancer. Imiquimod is approved for the treatment of actinic keratosis and basal cell carcinoma. The present investigation aimed to develop nanoemulsion-based gel with imiquimod (2.5% w/w) and carbopol ultrez 10 NF using a modified method to enhance the solubility, permeation, and therapeutic effectiveness of imiquimod to treat skin cancer. Combinations of rose oil and oleic acid, with Tween 20/Propylene glycol as Smix, were used in the formulation. The formulation underwent evaluation for parameters such as % drug content, in vitro drug diffusion studies, viscosity, skin irritation, in vitro cytotoxicity assay (MTT assay) and the DMBA/ croton oil skin cancer in vivo model.

Results

The formulation showed a minimum globule size of 118 nm, a zeta potential– 56.26 mV, a PDI of 0.378 and a drug content of 99.77%. In vitro drug release exhibited 45.00% of imiquimod release within 8 h, while approximately 34.32% release was found from the commercial cream. The imiquimod-loaded nanoemulsion-based gel showed significant cytotoxicity (p < 0.001) against the A431 cell line compared to Imiquad cream. The IC₅₀ value of the imiquimod-loaded nanoemulsion-based gel was noted to be 10.76 ± 2.54 µg/mL. In vivo results showed a significant reduction in tumor incidence (16.66%), tumor volume (140.26 ± 3.48 mm³), tumor burden (5.50 mm³) and tumor mass (0.66 ± 0.05 g) compared with the DMBA/croton oil carcinogen treatment control group. Histopathological finding showed the absence of keratinized pearls, epidermal hyperplasia, and acanthosis in the formulation treated group.

Conclusion

The results revealed that the nanoemulsion-based gel, with half the IMQ concentration of the commercial cream and incorporating Carbopol Ultrez 10NF, is a promising method for treating skin carcinogenesis. It potentially reduces dose-dependent side effects and demonstrating enhanced efficacy.

Graphical abstract

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开发和评估用于治疗皮肤癌的咪喹莫特纳米乳液凝胶

人体皮肤是人体最大的器官，对日常生活中遇到的许多化学诱变剂和致癌物质特别敏感。皮肤癌已成为一个值得关注的全球健康问题，部分原因是暴露于环境污染物和紫外线的机会增多。目前有多种治疗皮肤癌的方法。咪喹莫特已被批准用于治疗光化性角化病和基底细胞癌。本研究旨在采用一种改良方法，开发含有咪喹莫特（2.5% w/w）和 carbopol ultrez 10 NF 的纳米乳液凝胶，以提高咪喹莫特的溶解度、渗透性和治疗效果，从而治疗皮肤癌。配方中使用了玫瑰油和油酸的组合物，并以吐温 20/丙二醇作为 Smix。该制剂接受了药物含量百分比、体外药物扩散研究、粘度、皮肤刺激性、体外细胞毒性试验（MTT 试验）和 DMBA/ 巴豆油皮肤癌体内模型等参数的评估。制剂的最小球形尺寸为 118 纳米，zeta 电位为 56.26 mV，PDI 为 0.378，药物含量为 99.77%。体外药物释放显示，8 小时内咪喹莫特的释放率为 45.00%，而商用乳膏的释放率约为 34.32%。与咪喹莫特乳膏相比，负载纳米乳液的咪喹莫特凝胶对 A431 细胞株具有显著的细胞毒性（p < 0.001）。负载纳米乳液的咪喹莫特凝胶的 IC50 值为 10.76 ± 2.54 µg/mL。体内实验结果显示，与 DMBA/克罗恩油致癌物治疗对照组相比，肿瘤发病率（16.66%）、肿瘤体积（140.26 ± 3.48 mm3）、肿瘤负荷（5.50 mm3）和肿瘤质量（0.66 ± 0.05 g）均显著降低。组织病理学结果显示，制剂处理组没有出现角化珠状体、表皮增生和棘皮症。研究结果表明，纳米乳液凝胶的 IMQ 浓度仅为商用乳霜的一半，并含有 Carbopol Ultrez 10NF，是一种治疗皮肤癌的有效方法。它有可能减少剂量依赖性副作用，并显示出更强的疗效。

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来源期刊

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

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审稿时长

23 weeks

期刊介绍： Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.