Lobita Maria C, El-Sayed Nesma, Pinto João F, Santos Hélder A
Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands; W.J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, P.O. Box 56 (Viikinkaari 5 E), University of Helsinki, FI-00014 Helsinki, Finland; Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 21521 Alexandria, Egypt.
Int J Pharm. 2023 Jul 25;642:123143. doi: 10.1016/j.ijpharm.2023.123143. Epub 2023 Jun 15.
Delivery of cancer cell membranes (CM) is a new approach for the activation of the immune system and the induction of immunotherapy of cancer. Local delivery of melanoma CM into skin can induce efficient immune stimulation of antigen presenting cells (APCs), such as dendritic cells. In the current study, fast dissolving microneedles (MNs) were developed for the delivery of melanoma B16F10 CM. Two polymers were tested for the fabrication of MNs: poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) and hyaluronic acid (HA). The incorporation of CM in MNs was achieved through coating of the MNs using a multi-step layering procedure or the micromolding technique. The CM loading and its stabilization were improved by adding sugars (sucrose and trehalose) and a surfactant (Poloxamer 188), respectively. In an ex vivo experiment, both PMVE-MA and HA showed fast dissolutions (<30 s) after insertion into porcine skin. However, HA-MN showed better mechanical properties, namely improved resistance to fracture when submitted to a compression force. Overall, a B16F10 melanoma CM-dissolving MN system was efficiently developed as a promising device suggesting further studies in immunotherapy and melanoma applications.
递送癌细胞膜（CM）是激活免疫系统和诱导癌症免疫治疗的一种新方法。将黑色素瘤CM局部递送至皮肤可诱导抗原呈递细胞（APC），如树突状细胞产生有效的免疫刺激。在本研究中，开发了用于递送黑色素瘤B16F10 CM的速溶微针（MN）。测试了两种聚合物用于制造MN：聚（甲基乙烯基醚-共-马来酸）（PMVE-MA）和透明质酸（HA）。通过使用多步分层程序或微成型技术对MN进行包被，实现了CM在MN中的掺入。分别通过添加糖类（蔗糖和海藻糖）和表面活性剂（泊洛沙姆188）改善了CM的负载及其稳定性。在一项体外实验中，PMVE-MA和HA插入猪皮肤后均显示出快速溶解（<30秒）。然而，HA-MN表现出更好的机械性能，即在受到压缩力时具有更好的抗断裂性。总体而言，高效开发了一种B16F10黑色素瘤CM溶解MN系统，作为一种有前景的装置，表明在免疫治疗和黑色素瘤应用方面有待进一步研究。
