Sabri Akmal H, Smith Fiona, Cater Zachary, Gurnani Pratik, Nash Ami, Brentville Victoria, Durrant Lindy, McKenna John, Segal Joel, Scurr David J, Marlow Maria
School of Pharmacy, University of Nottingham, Nottingham, UK.
Advanced Manufacturing Technology Research Group, Faculty of Engineering, University of Nottingham, Nottingham, UK.
Drug Deliv. 2025 Dec;32(1):2527824. doi: 10.1080/10717544.2025.2527824. Epub 2025 Jul 10.
Topical therapy with imiquimod in a cream [5% w/w imiquimod cream (Aldara™)] for the treatment of nodular basal cell carcinoma (BCC) currently results in low cure rates, attributed to low imiquimod permeation. Herein we have developed novel microneedle array patches (MAPs), to maximize imiquimod intradermal delivery and retention in the skin, with potential as an efficacious treatment for BCC. Enhanced delivery of imiquimod in pig skin and BCC tissue was found with the obelisk poly N-acryloylmorpholine (pNAM) MAPs as compared to the 5% w/w imiquimod cream and MAPS manufactured from a commercially available polymer (PVPVA). Additionally, the increased retention in BCC tissue was found with the obelisk pNAM MAPs as compared to the 5% w/w imiquimod cream. In addition, detailed characterization of single needles and mechanistic studies of MAPs in tissue using mass spectrometry imaging confirmed the imiquimod homogeneity in the needles. Most importantly, the tumor efficacy study showed that pNAM obelisk MAPs could deliver imiquimod into the tumor, retarding tumor growth. This study suggests that the drug loaded obelisk pNAM MAPs manufactured here may be of clinical utility for localized intradermal delivery of imiquimod.
目前，使用咪喹莫特乳膏[5%（w/w）咪喹莫特乳膏（艾达乐™）]进行局部治疗结节性基底细胞癌（BCC）的治愈率较低，这归因于咪喹莫特的低渗透性。在此，我们开发了新型微针阵列贴片（MAPs），以最大限度地提高咪喹莫特在皮肤内的递送和保留，具有作为BCC有效治疗方法的潜力。与5%（w/w）咪喹莫特乳膏和由市售聚合物（PVPVA）制成的MAPs相比，发现方尖碑状聚N-丙烯酰吗啉（pNAM）MAPs能增强咪喹莫特在猪皮肤和BCC组织中的递送。此外，与5%（w/w）咪喹莫特乳膏相比，方尖碑状pNAM MAPs在BCC组织中的保留增加。此外，使用质谱成像对单根微针进行详细表征以及对组织中MAPs进行机制研究，证实了微针中咪喹莫特的均匀性。最重要的是，肿瘤疗效研究表明，pNAM方尖碑状MAPs可以将咪喹莫特递送至肿瘤中，延缓肿瘤生长。这项研究表明，在此制造的载药pNAM方尖碑状MAPs可能在临床上用于咪喹莫特的局部皮内递送。
