Biodegradable Sustained-Release Microneedle Patch Loaded with Clindamycin Hydrochloride：A Breakthrough in Acne Management

Haomei Fan¹Ruohan Liao²Yiling Yang²Yan Xing³Chengdong Zhang⁴Xuwei Luo³Chao Pu³Liling WU³Xingping Li^5*Juhua Zhao^3*Dongqin Xiao^4*

• ¹Mianyang Maternal and Child Health Hospital, Mianyang, China
• ²North Sichuan Medical College, Nanchong, China
• ³the Second Clinical College of North Sichuan Medical College, Nanchong, China
• ⁴Research Institute of Tissue Engineering and Stem Cells, the Second Clinical College of North Sichuan Medical College, Nanchong, Shanxi Province, China
• ⁵Department of Orthopaedics, Chengfei Hospital,, Chengdu,, China

Background: 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), Fouriertransform 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 ex vivo 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 (C. acnes) was measured via colony counting. In vivo 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.Results: 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 C. acnes (bacterial inhibition rate of 100%). In vivo 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.