3D-printed acyclovir nanocrystals: An advanced approach to herpes simplex treatment

• ACV has low topical bioavailability, limiting its effectiveness in herpes treatments. • 3D printing technology was used to produce patches with ACV NCs. • PVP allows the obtaining of NCs of <200 nm and PDI <0.2, stables for 30 days. • NCs patches exhibit a more uniform drug distribution compared to PM patches. • NCs patch shows better biocompatibility and higher mucosal deposition than PM patch. The Herpesviridae family includes a major group of double-stranded DNA viruses, with herpes simplex virus (HSV) causing orofacial herpes, which affects 66.6 % of people aged 0 to 49. Acyclovir (ACV) is central to HSV management, yet its low topical bioavailability and poor skin penetration limit its effectiveness. This study explores the development of 3D-printed sodium alginate patches loaded with media-milled ACV nanocrystals (NCs). Screening of stabilising agents identified 0.5 % w/v polyvinylpyrrolidone as optimal, yielding NCs with a particle size of 145.4 ± 1.2 nm and polydispersity index of 0.117. Stability tests confirmed over 30 days of stability, and physicochemical studies demonstrated that crystallinity maintained pre- and post-milling. Morphological assessments using optical and scanning electron microscopy, along with optical coherence tomography revealed a uniform, compact structure in ACV-NCs patches, while mechanical testing indicated greater elasticity compared to patches with a physical mixture. In vitro release studies showed no significant differences, but ex vivo mucosal deposition on neonatal porcine mucosa showed NCs patches had significantly higher drug deposition compared to a physical mixture (13 % vs. 6 %). This innovative approach offers a promising topical therapy for herpes cold sores, addressing the need for more effective treatments.