Biodegradable sustained-release microneedle patch loaded with clindamycin hydrochloride: a breakthrough in acne management

Abstract

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.

Keywords: GelMA hydrogel; acne vulgaris; clindamycin hydrochloride; minimally invasive drug delivery system; swellable microneedles.

FIGURE 1

Schematic illustration of the formation and mechanism of GM-Clin-MN patch for acne vulgaris treatment.

FIGURE 2

Fabrication and characterization of GelMA. (a) Schematic illustration of the preparation procedures for GelMA. (b) The chemical synthesis principle of GelMA. (c) NMR spectra of gelatin and GelMA. (d) Verification of the photo-crosslinking characteristics of GelMA.

FIGURE 3

Fabrication and characterization of GM-Clin-MN. (a) Schematic illustration of the preparation procedures for GM-Clin-MN. (b–e) Digital photograph of the GM-Clin-MN patch (f,g) SEM images of GM-Clin-MN. (h,i) Fluorescence microscopy images showing rhodamine-labeled MN. (j) FT-IR spectra of GM-Clin-MN, GM-MN and Clin. (k) Schematic diagram of GM-Clin-MN (red arrow) enclosed in a dialysis bag submerged in phosphate buffer solution (l) In vitro release curve of clindamycin hydrochloride. (m) Mechanical strength-displacement curve of the microneedles. (n) Image of rat abdomen skin after piercing with microneedles labeled with Rhodamine 6G. (o) Histopathological image of skin after microneedle piercing, stained with hematoxylin and eosin (H&E). (p) Optical microscopy images of microneedle tip morphology at different time points after insertion into the skin.

FIGURE 4

In vitro biological performance evaluation of GelMA. (a) Comparative images of in vitro antimicrobial experiment of microneedles against C. acnes. (b) Cell viability after culture for 1, 4 and 7 days. (c) Comparative images of HET-CAM irritation tests. ns: no significant differences, indicates p > 0.05 (n = 3).

FIGURE 5

In vivo evaluation of GM-Clin-MN treatment for rat ear acne. (a) Time course diagram of acne animal treatment. Qd: once a day. Qod: every other day. Bid: twice a day. (b) Normal rat ear. (c) Rat ear after acne induction. (d) Illustration of microneedles applied to the rat ear for acne treatment. (e) Comparative image after acne treatment in rats. (PBS: negative control group. GM-MN: blank microneedle group). (f) Changes in rat ear thickness with treatment duration.

FIGURE 6

(a) Histological images of treated acne rat model tissue stained with HE (×200). (b) Protein expression levels of IL-1β, MMP-2, and IL-10 in rat ear tissue among different groups. (c) Comparative graph of IL-1β protein expression IOD (Integrated Optical Density) values. (d) Comparative graph of MMP-2 protein expression IOD values. (e) Comparative graph of IL-10 protein expression IOD values. (* indicates p < 0.05, ** indicates p < 0.01, *** indicates p < 0.001; n = 3).