Lee Jin Sil, Oh Hyeryeon, Kim Sunghyun, Lee Jeung-Hoon, Shin Yong Chul, Choi Won Il
Center for Convergence Bioceramic Materials, Convergence R&D Division, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Korea.
School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Cheomdan-gwagiro 123, Buk-gu, Gwangju 61005, Korea.
Pharmaceutics. 2021 Aug 25;13(9):1329. doi: 10.3390/pharmaceutics13091329.
Transepidermal drug delivery achieves high drug concentrations at the action site and ensures continuous drug delivery and better patient compliance with fewer adverse effects. However, drug delivery through topical application is still limited in terms of drug penetration. Chitosan is a promising enhancer to overcome this constraint, as it can enhance drug diffusion by opening the tight junctions of the stratum corneum. Therefore, here, we developed a novel chitosan nanosponge (CNS) with an optimal ratio and molecular weight of chitosan to improve drug penetration through skin. To prepare the CNS, two types of chitosan (3 and 10 kDa) were each conjugated with poloxamer 407 using para-nitrophenyl chloroformate, and the products were mixed with poloxamer 407 at ratios of 5:5, 8:2, and 10:0. The resulting mixtures were molded to produce flexible soft nanosponges by simple nanoprecipitation. The CNSs were highly stable in biological buffer for four weeks and showed no toxicity in human dermal fibroblasts. The CNSs increased drug permeability through human cadaver skin in a Franz-type diffusion cell, with substantially higher permeability with 3 kDa chitosan at a ratio of 8:2. This suggests the applicability of the novel CNS as a promising carrier for efficient transepidermal drug delivery.
经皮给药可在作用部位实现高药物浓度，并确保持续给药，提高患者依从性，且副作用更少。然而，局部给药在药物渗透方面仍存在局限性。壳聚糖是一种很有前景的增强剂，可克服这一限制，因为它能通过打开角质层的紧密连接来增强药物扩散。因此，在此我们开发了一种新型壳聚糖纳米海绵（CNS），其壳聚糖比例和分子量最佳，以提高药物经皮肤的渗透率。为制备CNS，使用对硝基苯基氯甲酸酯将两种类型的壳聚糖（3 kDa和10 kDa）分别与泊洛沙姆407偶联，并将产物与泊洛沙姆407按5:5、8:2和10:0的比例混合。通过简单的纳米沉淀将所得混合物成型，以制备柔性软纳米海绵。CNS在生物缓冲液中高度稳定达四周，且对人皮肤成纤维细胞无毒性。在弗兰兹型扩散池中，CNS提高了药物通过人尸体皮肤的渗透率，其中壳聚糖比例为8:2的3 kDa壳聚糖表现出显著更高的渗透率。这表明新型CNS作为高效经皮给药的有前景载体具有适用性。
