Moreno Víctor M, Meroño Carolina, Baeza Alejandro, Usategui Alicia, Ortiz-Romero Pablo L, Pablos José L, Vallet-Regí María
Departamento de Química en Ciencias Farmacéuticas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
CIBER de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, 28029 Madrid, Spain.
Pharmaceutics. 2021 Apr 6;13(4):499. doi: 10.3390/pharmaceutics13040499.
Peyronie and Dupuytren are pathologies characterized by the appearance of localized fibrotic lesions in an organ. These disorders originate from an excessive production of collagen in the tissue provoking dysfunction and functional limitations to the patients. Local administration of collagenase is the most used treatment for these fibrotic-type diseases, but a high lability of the enzyme limits its therapeutic efficacy. Herein, we present a novel methodology for the preparation of collagenase nanocapsules without affecting its enzymatic activity and capable of releasing the enzyme in response to an ultraviolet A (UVA) light stimulus. Polymeric coating around collagenase was formed by free-radical polymerization of acrylamide-type monomers. Their degradation capacity under UVA irradiation was provided by incorporating a novel photocleavable acrylamide-type crosslinker within the polymeric framework. This property allowed collagenase release to be triggered in a controlled manner by employing an easily focused stimulus. Additionally, UVA irradiation presents considerable benefits by itself due to its capacity to induce collagenase production in situ. An expected synergistic effect of collagenase nanocapsules in conjunction with UVA effect may present a promising treatment for these fibrotic diseases.
佩罗尼氏病和迪皮特朗挛缩症是一类以器官内出现局部纤维化病变为特征的病症。这些疾病源于组织中胶原蛋白的过度生成,给患者带来功能障碍和功能限制。局部施用胶原酶是治疗这类纤维化疾病最常用的方法,但该酶的高不稳定性限制了其治疗效果。在此,我们提出了一种制备胶原酶纳米胶囊的新方法,该方法不会影响其酶活性,并且能够响应紫外线A(UVA)光刺激释放酶。胶原酶周围的聚合物涂层通过丙烯酰胺类单体的自由基聚合形成。通过在聚合物骨架中引入一种新型的可光裂解丙烯酰胺类交联剂,赋予了它们在UVA照射下的降解能力。这种特性使得通过采用易于聚焦的刺激能够以可控方式触发胶原酶释放。此外,UVA照射本身具有显著优势,因为它能够原位诱导胶原酶生成。胶原酶纳米胶囊与UVA效应相结合所产生的预期协同效应可能为这些纤维化疾病提供一种有前景的治疗方法。