在本研究中，制备了携带紫杉醇（PTX）和替莫唑胺（TMZ）的纳米凝胶乳霜，用于局部治疗黑色素瘤。PTX和TMZ首先载入聚左右旋乳酸-聚乙二醇-聚左右旋乳酸-聚乙二醇（PLAG-b-PEG-b-PLGA）温敏的纳米凝胶中，该凝胶从25°C的自由流动溶胶（形成胶束网络）转变为33°C的凝胶（胶束聚集），其z平均粒径约为96 nm至427 nm。接着，将无水吸收膏基础物质Aquaphor加入药物载体纳米凝胶中，形成携带PTX和TMZ的纳米凝胶乳霜。与纳米凝胶药物负载的组分相比，纳米凝胶乳霜可控释药，能够使药物在啮齿动物皮肤中更好地渗透。体外实验证明，PTX和TMZ的联合使用对SK-MEL28、A375和B16-F10黑色素瘤细胞具有协同抑制作用。体内实验证明，局部涂抹携带TMZ/PTX（4 mg/1.5 mg/剂量）的纳米凝胶乳霜，可能对B16-F10移植瘤小鼠的肿瘤体积产生抑制作用。© 2023. 作者发表，独家授权施普林格科学+商业媒体有限责任公司，隶属于施普林格自然。

In this study, nanogel creams carrying paclitaxel (PTX) and temozolomide (TMZ) were prepared for the topical treatment of melanoma. PTX and TMZ were first loaded in poly-(D,L-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLAG-b-PEG-b-PLGA) thermosensitive nanogels, which made a transition from a free-flowing sol (formation of micellar network) at 25°C with the z-average particle size of c.a. 96 nm to a gel (aggregation of micelles) at 33°C with the z-average particle size of c.a. 427 nm. An anhydrous absorption ointment base, aquaphor, was then added to drug-loaded nanogels to form nanogel creams carrying PTX and TMZ. Nanogel creams permitted controlled release of the payloads and improved the penetration of the payloads through the rodent skin compared to drug(s)-loaded nanogels. PTX and TMZ in a combination were synergistically effective in inhibiting SK-MEL28, A375, and B16-F10 melanoma cancer cells in vitro. Topically applied nanogel creams carrying TMZ/PTX (4 mg/1.5 mg/dose) showed a trend of tumor volume inhibition on B16-F10-bearing xenograft mice in vivo.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.