Kim Suyong, Dangol Manita, Kang Geonwoo, Lahiji Shayan F, Yang Huisuk, Jang Mingyu, Ma Yonghao, Li Chengguo, Lee Sang Gon, Kim Chang Hyun, Choi Young Wook, Kim So Jeong, Ryu Ja Hyun, Baek Ji Hwoon, Koh Jaesuk, Jung Hyungil
Department of Biotechnology, Yonsei University , Building 123, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Juvic Inc., Yonsei Engineering Research Park , Building 102, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Mol Pharm. 2017 Jun 5;14(6):2024-2031. doi: 10.1021/acs.molpharmaceut.7b00111. Epub 2017 May 5.
Dissolving microneedle (DMN), a transdermal drug delivery system in which drugs are encapsulated in a biodegradable polymeric microstructure, is designed to dissolve after skin penetration and release the encapsulated drugs into the body. However, because of limited loading capacity of drugs within microsized structures, only a small dosage can be delivered, which is often insufficient for patients. We propose a novel DMN application that combines topical and DMN application simultaneously to improve skin permeation efficiency. Drugs in pretreated topical formulation and encapsulated drugs in DMN patch are delivered into the skin through microchannels created by DMN application, thus greatly increasing the delivered dose. We used 4-n-butylresorcinol to treat human hyperpigmentation and found that sequential application of serum formulation and DMNs was successful. In skin distribution experiments using Alexa Fluor 488 and 568 dyes as model drugs, we confirmed that the pretreated serum formulation was delivered into the skin through microchannels created by the DMNs. In vitro skin permeation and retention experiments confirmed that this novel combined application delivered more 4-n-butylresorcinol into the skin than traditional DMN-only and serum-only applications. Moreover, this combined application showed a higher efficacy in reducing patients' melanin index and hyperpigmented regions compared with the serum-only application. As combined application of DMNs on serum-treated skin can overcome both dose limitations and safety concerns, this novel approach can advance developments in transdermal drug delivery.
溶蚀性微针（DMN）是一种经皮给药系统，其中药物被包裹在可生物降解的聚合物微结构中，其设计目的是在穿透皮肤后溶解，并将包裹的药物释放到体内。然而，由于微尺寸结构内药物的负载能力有限，只能递送小剂量药物，这对患者来说往往是不够的。我们提出了一种新型的DMN应用方法，即同时联合局部给药和DMN给药，以提高皮肤渗透效率。预处理局部制剂中的药物和DMN贴剂中包裹的药物通过DMN应用产生的微通道递送至皮肤，从而大大增加了给药剂量。我们使用4-正丁基间苯二酚治疗人类色素沉着，发现依次应用血清制剂和DMN是成功的。在使用Alexa Fluor 488和568染料作为模型药物的皮肤分布实验中，我们证实预处理的血清制剂通过DMN产生的微通道递送至皮肤。体外皮肤渗透和滞留实验证实，这种新型联合应用比传统的仅使用DMN和仅使用血清的应用将更多的4-正丁基间苯二酚递送至皮肤。此外，与仅使用血清的应用相比，这种联合应用在降低患者黑色素指数和色素沉着区域方面显示出更高的疗效。由于在血清处理过的皮肤上联合应用DMN可以克服剂量限制和安全性问题，这种新方法可以推动经皮给药的发展。
