Stearic acid nanoparticles increase acyclovir absorption by oral epithelial cells.

Objective: Acyclovir (ACY) is used to treat oral viral herpes but has low solubility and bioavailability. Stearic acid (SA) is lipophilic and can be combined with drugs. Therefore, this study aimed to characterize the properties of SA nanoparticles in increasing the cellular uptake of ACY by oral epithelial cells. The hypothesis was that SA nanoparticles increase sustained ACY release, are stable, and increase drug uptake.

Methods: The production parameters (duration and amplitude of sonication) were optimized to produce solid lipid nanoparticles (SLN) of SA-containing ACY. Particle stability was characterized under different storage conditions (4 °C and 37 °C for 1, 15, and 45 days). SLN were further characterized for their pharmacokinetic profile, cytotoxicity, in vitro permeability, and ability to modulate gene expression and promote ACY uptake by oral epithelial cells.

Results: Pharmacokinetic studies revealed sustained and diffusional release of ACY from the SLN, with an initial burst release of 15 min. After 45 d of storage, SLN kept at both 4 °C and 37 °C showed a maximum release of > 90 % of the drug at 120 min. Cells treated with SLN presented a significantly higher intracellular drug content than those treated with ACY and significantly increased the genetic expression of TJP-1, OCLN, and ECAD.

Significance: The hypothesis was accepted as SA nanoparticles containing ACY can sustain drug delivery and enhance its absorption into epithelial cells. Therefore, SA nanoparticles are promising for improving ACY uptake in treating oral herpes and other infections caused by HSV-1.