Fan Haomei, Liao Ruohan, Yang Yiling, Xing Yan, Zhang Chengdong, Luo Xuwei, Pu Chao, Wu Liling, Li Xingping, Zhao Juhua, Xiao Dongqin
Department of Dermatology, Research Institute of Tissue Engineering and Stem Cells, The Second Clinical College of North Sichuan Medical College, Nanchong, China.
School of Clinical Medicine, Southwest Medical University, Luzhou, China.
Front Pharmacol. 2025 May 30;16:1575635. doi: 10.3389/fphar.2025.1575635. eCollection 2025.
Clindamycin hydrochloride, a first-line antibiotic for acne treatment, faces challenges with poor skin penetration due to its hydrophilicity and the barrier posed by the stratum corneum. To address this limitation, we developed gelatin-methacryloyl (GelMA) hydrogel-based biodegradable microneedles (GM-Clin-MN) for sustained intradermal drug delivery, thereby enhancing therapeutic efficacy.
The microneedle patches loaded with 1 wt% clindamycin hydrochloride were fabricated using PDMS molds and characterized through scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and fluorescence microscopy. Drug loading and release were assessed using UV-Vis spectroscopy at 520 nm, while mechanical strength was evaluated with a universal testing machine. Skin penetration was tested on rat abdominal skin. Biosafety was determined through human skin fibroblast (HSF) cytotoxicity and hen's egg test-chorioallantoic membrane (HET-CAM) irritation tests. Antibacterial efficacy against Cutibacterium acnes () was measured via colony counting. acne treatment of the microneedles was evaluated in a rat acne model. Gross morphological changes, histological sections, and immunohistochemical staining were used to evaluate the efficacy and potential mechanisms of acne treatment.
Clindamycin hydrochloride-loaded GelMA microneedles (GM-Clin-MN) achieved a drug loading of 0.49 ± 0.025 μg/needle, exhibiting rapid release on Day 1 (54.8% ± 2.1%) and sustained release by Day 10 (72.1% ± 1.5%). The microneedles penetrated the skin to a depth of 658 ± 66 μm, swelled by 185.4% ± 12.1%, and completely dissolved within 10 min. GM-Clin-MN displayed no cytotoxicity or skin irritation and effectively inhibited the growth of (bacterial inhibition rate of 100%). studies revealed that acne-related inflammation was effectively suppressed with potential anti-scarring properties, characterized by reduced pro-inflammatory IL-1β levels, increased anti-inflammatory IL-10 expression, and diminished MMP-2 activity - a key enzyme in collagen overproduction during scarring.
GM-Clin-MN enables sustained, minimally invasive clindamycin delivery through the stratum corneum, offering a dual-action therapeutic strategy that combines potent antibacterial activity with anti-inflammatory modulation for acne management.
盐酸克林霉素是治疗痤疮的一线抗生素,由于其亲水性和角质层形成的屏障,皮肤渗透性较差,面临挑战。为解决这一局限性,我们开发了基于明胶-甲基丙烯酰基(GelMA)水凝胶的可生物降解微针(GM-Clin-MN)用于持续皮内给药,从而提高治疗效果。
使用聚二甲基硅氧烷(PDMS)模具制备负载1 wt%盐酸克林霉素的微针贴片,并通过扫描电子显微镜(SEM)、傅里叶变换红外光谱(FTIR)和荧光显微镜进行表征。使用紫外可见光谱在520 nm处评估药物负载和释放,同时用万能试验机评估机械强度。在大鼠腹部皮肤进行皮肤渗透性测试。通过人皮肤成纤维细胞(HSF)细胞毒性和鸡胚绒毛尿囊膜(HET-CAM)刺激试验确定生物安全性。通过菌落计数测量对痤疮丙酸杆菌的抗菌效果。在大鼠痤疮模型中评估微针的痤疮治疗效果。使用大体形态变化、组织切片和免疫组织化学染色来评估痤疮治疗的效果和潜在机制。
负载盐酸克林霉素的GelMA微针(GM-Clin-MN)的药物负载量为每根微针0.49±0.025μg,在第1天表现出快速释放(54.8%±2.1%),到第10天持续释放(72.1%±1.5%)。微针刺入皮肤深度为658±66μm,肿胀185.4%±12.1%,并在10分钟内完全溶解。GM-Clin-MN没有显示出细胞毒性或皮肤刺激性,并有效抑制痤疮丙酸杆菌的生长(细菌抑制率为100%)。研究表明,与痤疮相关的炎症得到有效抑制,具有潜在的抗瘢痕特性,表现为促炎细胞因子IL-1β水平降低、抗炎细胞因子IL-10表达增加以及基质金属蛋白酶-2(MMP-2)活性降低,MMP-2是瘢痕形成过程中胶原蛋白过度产生的关键酶。
GM-Clin-MN能够通过角质层实现持续、微创的克林霉素给药,提供一种双重作用的治疗策略,将强效抗菌活性与抗炎调节相结合用于痤疮管理。