Jin Youmei, Zhang Chi, Jia Mengnan, Chen Ming
Department of Marine Biological Science & Technology, College of Ocean & Earth Sciences, Xiamen University, Xiamen, 361102, People's Republic of China.
State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, Xiamen University, Xiamen, 361102, People's Republic of China.
Int J Nanomedicine. 2025 Mar 14;20:3235-3249. doi: 10.2147/IJN.S509798. eCollection 2025.
The pathogenesis of atopic dermatitis (AD) is closely linked to both genetic and environmental factors, with patients often exhibiting a range of immunological abnormalities, including a pronounced Th2-type overreaction, which is a key feature of the disease.
has been shown to induce a robust Th1 immune response through intraperitoneal injections, potentially preventing the development of AD. In this study, a novel nanoparticulate formulation of (NFCA) was developed with the formulation optimization for the dermal delivery.
Sponge sp. spicules (SHS) were isolated from the explants of sponge . with our proprietary method. The NFCA was prepared by high-speed grinding followed by film extrusion. The skin penetration of the model drugs in NFCA with SHS were visualized using confocal microscopy. The therapeutic effects of NFCA coupled with SHSs against AD in mice were assessed by using pathohistological examination and cytokine ELISA assay.
The NFCA particle size was 254.1±39.4 nm, with a PDI of 0.29±0.08 and a Zeta potential of -7.9±0.6 mV. SHS significantly enhanced total skin absorption of FD10K (39.6±6.7%, =0.00076) as well as deposition in the viable epidermis (3.2±1.6%, =0.08) and deep skin (dermis & receptor) (36.0±5.9%, =1.82E-5) compared to the control. In vitro cytotoxicity tests showed that NFCA had low toxicity to HaCaT cells (IC50=63.8 mg/mL). The study confirmed that NFCA can activate immune signaling pathways, promoting the high expression of IL-6 and IL-8 in keratinocytes, enhancing TNF-α and IL-1β expression in macrophages, and inducing Th1 and Th17-type immune responses. Furthermore, we demonstrated that the dermal delivery of NFCA using SHS in vivo significantly reduced epidermal thickness, serum IgE levels, and tissue IL-4 levels, thereby accelerating skin repair and mitigating Th2 polarization.
SHS were employed to effectively deliver NFCA to the deeper skin layers to exert its immune functions. Moreover, the combination of SHS and NFCA can significantly cure mice with atopic dermatitis.
特应性皮炎（AD）的发病机制与遗传和环境因素密切相关，患者常表现出一系列免疫异常，包括明显的Th2型过度反应，这是该疾病的一个关键特征。
已证明通过腹腔注射可诱导强烈的Th1免疫反应，有可能预防AD的发生。在本研究中，开发了一种新型的纳米颗粒制剂（NFCA），并对其进行了用于皮肤给药的制剂优化。
采用我们的专有方法从海绵的外植体中分离出海绵骨针（SHS）。通过高速研磨然后薄膜挤出制备NFCA。使用共聚焦显微镜观察模型药物在含SHS的NFCA中的皮肤渗透情况。通过病理组织学检查和细胞因子ELISA测定评估含SHS的NFCA对小鼠AD的治疗效果。
NFCA粒径为254.1±39.4nm，多分散指数（PDI）为0.29±0.08，zeta电位为-7.9±0.6mV。与对照组相比，SHS显著提高了FD10K的皮肤总吸收量（39.6±6.7%，P = 0.00076）以及在活表皮中的沉积量（3.2±1.6%，P = 0.08）和深层皮肤（真皮和受体层）中的沉积量（36.0±5.9%，P = 1.82E - 5）。体外细胞毒性试验表明，NFCA对HaCaT细胞毒性较低（半数抑制浓度IC50 = 63.8mg/mL）。该研究证实，NFCA可激活免疫信号通路，促进角质形成细胞中IL - 6和IL - 8的高表达，增强巨噬细胞中TNF - α和IL - 1β的表达，并诱导Th1和Th17型免疫反应。此外，我们证明在体内使用SHS进行NFCA的皮肤给药可显著降低表皮厚度、血清IgE水平和组织IL - 4水平，从而加速皮肤修复并减轻Th2极化。
采用SHS有效地将NFCA递送至更深层皮肤以发挥其免疫功能。此外，SHS与NFCA的组合可显著治愈特应性皮炎小鼠。
