Abstract：
Hair follicle-penetrating nanoparticles offer a promising avenue for targeted antibiotic delivery, especially in challenging infections like acne inversa or folliculitis decalvans. However, demonstrating their efficacy with existing preclinical models remains difficult. This study presents an innovative approach using a 3D in vitro organ culture system with human hair follicles to investigate the hypothesis that antibiotic nanocarriers may reach bacteria within the follicular cleft more effectively than free drugs. Living human hair follicles were transplanted into a collagen matrix within a 3D printed polymer scaffold to replicate the follicle\'s microenvironment. Hair growth kinetics over 7 days resembled those of simple floating cultures. In the 3D model, fluorescent nanoparticles exhibited some penetration into the follicle, not observed in floating cultures. Staphylococcus aureus bacteria displayed similar distribution profiles postinfection of follicles. While rifampicin-loaded lipid nanocapsules were as effective as free rifampicin in floating cultures, only nanoencapsulated rifampicin achieved the same reduction of CFU/mL in the 3D model. This underscores the hair follicle microenvironment\'s critical role in limiting conventional antibiotic treatment efficacy. By mimicking this microenvironment, the 3D model demonstrates the advantage of topically administered nanocarriers for targeted antibiotic therapy against follicular infections.
摘要：
毛囊穿透性纳米粒子为靶向抗生素递送提供了有希望的途径，尤其是在具有挑战性的感染中，如痤疮或毛囊炎。然而,用现有的临床前模型证明其疗效仍然很困难.这项研究提出了一种使用3D体外器官培养系统与人毛囊的创新方法，以研究抗生素纳米载体可能比游离药物更有效地到达毛囊裂隙内的细菌的假设。将活体人类毛囊移植到3D打印聚合物支架内的胶原蛋白基质中，以复制毛囊的微环境。7天的头发生长动力学类似于简单的漂浮培养物。在3D模型中，荧光纳米粒子表现出一些渗透到毛囊中，在漂浮文化中没有观察到。金黄色葡萄球菌在卵泡感染后表现出相似的分布特征。虽然负载利福平的脂质纳米胶囊在漂浮培养物中与游离利福平一样有效，只有纳米封装的利福平在3D模型中实现了相同的CFU/mL降低。这强调了毛囊微环境在限制常规抗生素治疗功效中的关键作用。通过模仿这个微环境，3D模型证明了局部施用纳米载体用于靶向抗生素治疗卵泡感染的优势.
