TY - JOUR
T1 - 3D-printed acyclovir nanocrystals: an advanced approach to herpes simplex treatment
AU - Lopez-Vidal, Lucia
AU - Juskaite, Kornelija
AU - Fandino, Octavio
AU - Fuster, Marta G.
AU - Sangalli, Martina
AU - Adhami, Masoud
AU - Wang, Jiawen
AU - Palma, Santiago D.
AU - Volpe-Zanutto, Fabiana
AU - Larrañeta, Eneko
AU - Paredes, Alejandro J.
PY - 2025/4/7
Y1 - 2025/4/7
N2 - 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.
AB - 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.
KW - 3D-printed
KW - acyclovir
KW - nanocrystals
U2 - 10.1016/j.apmt.2025.102695
DO - 10.1016/j.apmt.2025.102695
M3 - Article
SN - 2352-9415
VL - 44
JO - Applied Materials Today
JF - Applied Materials Today
M1 - 102695
ER -