Microneedling-Assisted Drug Delivery: A Systematic Review and Meta-analysis With Biochemical, Histologic, and Ultrastructure Imaging Correlation.

BACKGROUND: Microneedling is gaining popularity in dermatologic practice to enhance transdermal drug delivery, yet key determinants of its efficacy-microneedle characteristics, drug properties, and the sequence of drug application-remain poorly understood. OBJECTIVE: The authors conducted a systematic review and meta-analysis to identify factors affecting efficacy of microneedling-assisted drug delivery measured using biochemical (Franz diffusion studies) or visual (histology and advanced imaging) methods. MATERIALS AND METHODS: PubMed, Web of Science, and Cochrane Library were searched through May 1, 2025. Data were abstracted on microneedling characteristics, treatment sequences, and drug characteristics. The authors performed a meta-analysis of Franz diffusion experiments to evaluate the efficacy and meta-regression to identify microneedle or drug factors influencing the efficacy. RESULTS: Twenty-nine articles were included. Microneedling enhances drug delivery (standard mean difference [95% confidence interval], 4.61 [2.99-6.24]). Delivery was greater for hydrophilic drugs (6.56 [2.28-10.85]) than for hydrophobic drugs (3.49 [2.43-4.56]) (p = .014). Longer needle lengths (≥500 μm; 5.96 [3.33-8.60] vs 2.77 [2.05-3.49] for <500 μm, p = .02) and drug application before microneedling (1.64 [1.00-2.28] vs 0.38 [-0.24 to 1.00] for drug after microneedling, p = .01) increased drug delivery. CONCLUSION: Clinicians should consider needle length, drug hydrophilicity, and treatment sequence to enhance microneedling-assisted drug delivery.