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Biodegradable sustained-release microneedle patch loaded with clindamycin hydrochloride: a breakthrough in acne
Haomei Fan1,2,3, Ruohan Liao1, Yiling Yang1
1Department of Dermatology, Research Institute of Tissue Engineering and Stem Cells, The Second Clinical College of North Sichuan Medical College, Nanchong, 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.
Methods:
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 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.
Conclusion:
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.
