APPLICATION OF ACYCLOVIR TO THE ORAL MUCOSA: MECHANISMS, PRE-CLINICAL EVIDENCE AND CLINICAL UTILITY
Keywords:
Keywords: acyclovir • oral mucosa • herpes simplex • nanofibre patch • wound healing • mucositisAbstract
Topical and locally delivered acyclovir (ACV) remain first-line interventions for herpes-related oral mucosal disease, yet their place alongside novel wound-healing strategies has evolved over the past decade. We systematically reviewed in-vitro, in-vivo and clinical studies published 1 January 2015 – 31 March 2025 in PubMed, Scopus, Web of Science, eLIBRARY, CyberLeninka and RSCI. Twenty-four eligible records (11 laboratory, 3 animal, 8 randomised controlled trials, 1 cohort and 1 network meta-analysis) were critically appraised with RoB 2/ROBINS-I and synthesised with GRADE methodology. ACV inhibits herpes-viral DNA polymerase after viral thymidine-kinase-triggered phosphorylation, halting replication and secondarily reducing inflammation. Nanocarriers (solid-lipid nanoparticles, nanofibres, muco-adhesive films) increased transepithelial uptake 3- to 5-fold in vitro and restored tight-junction protein expression. A rat HSV-1 oral-wound model showed accelerated re-epithelialisation with topical ACV versus control. Five human RCTs demonstrated that adjuncts (honey, clobetasol, photobiomodulation) shortened lesion healing by 1–3 days compared with ACV monotherapy. Prophylactic oral ACV halved chemotherapy-induced oral mucositis incidence in autologous stem-cell recipients. Low-level diode laser out-performed 5 % ACV cream for pain and recovery time. Adverse effects were limited to mild local irritation; systemic nephro-/neuro-toxicity was not observed with topical use. Evidence certainty was moderate (downgraded for sample size and heterogeneity). ACV remains the benchmark for HSV-related oral lesions, but efficacy is enhanced by anti-inflammatory or bio-adhesive technologies. Future trials should standardise endpoints and explore non-herpetic indications.
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