Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Pharmaceutics and Biopharmaceutics, Philipps-Universität Marburg, Marburg, Germany.
Max Planck Institute for Polymer Research, Mainz, Germany.
Int J Pharm. 2021 Mar 15;597:120339. doi: 10.1016/j.ijpharm.2021.120339. Epub 2021 Feb 2.
Hair follicles (HFs) are important drug delivery targets for the therapy of miscellaneous skin diseases and for skin antisepsis. Furthermore, HFs significantly contribute to drug delivery of topically applied substances. Nanoparticulate systems are excellently suited for follicular drug delivery as they entail the opportunity of directed drug transport into HFs. Moreover, they involve the possibility of an intrafollicular drug release initiated by extrinsic or intrinsic trigger mechanisms. In this study, we present a novel preclinical model for an anatomically and temporally targeted intrafollicular drug release. In vitro release kinetics of the model drug sulforhodamine 101 (SR101) from newly synthesized ultraviolet A (UVA)-responsive polyurethane nanocapsules (NCs) were investigated by fluorescence spectroscopy. Low power density UVA radiation provided by a UVA light emitting diode (LED) induced a drug release of over 50% after 2 min. We further utilized confocal laser scanning microscopy (CLSM) to investigate follicular penetration as well as intrafollicular drug release on an ex vivo porcine ear skin model. UVA-responsive degradation of the NCs at a mean follicular penetration depth of 509 ± 104 µm ensured liberation of SR101 in the right place and at the right time. Thus, for the first time a UVA-triggered drug release from NCs within HFs was demonstrated in the present study. Cytotoxicity tests revealed that NCs synthesized with isophorone diisocyanate show sufficient biocompatibility after UVA-induced cleavage. A considerable and controllable release of various water-soluble therapeutics could be reached by means of the presented system without risking any radiation-related tissue damage. Therefore, the implementation of the presented system into clinical routine, e.g. for preoperative antisepsis of HFs, appears very promising.
毛囊是治疗各种皮肤疾病和皮肤抗菌的重要药物输送靶标。此外，毛囊对局部应用物质的药物输送有重要贡献。纳米颗粒系统非常适合毛囊药物输送，因为它们有机会将药物定向输送到毛囊中。此外，它们还可以通过外在或内在触发机制引发毛囊内药物释放。在本研究中，我们提出了一种新的临床前模型，用于进行解剖学和时间靶向的毛囊内药物释放。通过荧光光谱法研究了模型药物磺基罗丹明 101（SR101）从新合成的紫外线 A（UVA）响应型聚氨酯纳米胶囊（NC）中的体外释放动力学。低功率密度的 UVA 辐射由 UVA 发光二极管（LED）提供，在 2 分钟后引发超过 50%的药物释放。我们进一步利用共聚焦激光扫描显微镜（CLSM）研究了离体猪耳皮肤模型中的毛囊穿透以及毛囊内药物释放。NC 在平均毛囊穿透深度 509±104µm 处的 UVA 响应性降解确保了 SR101 在正确的位置和时间释放。因此，本研究首次证明了 NC 中的 UVA 触发药物在毛囊内释放。细胞毒性试验表明，在 UVA 诱导裂解后，使用异佛尔酮二异氰酸酯合成的 NC 具有足够的生物相容性。通过所提出的系统，可以实现各种水溶性治疗药物的可控释放，而不会有任何与辐射相关的组织损伤的风险。因此，将所提出的系统应用于临床常规，例如用于毛囊的术前抗菌，似乎非常有前途。
