Acyclovir

Silva Ana C.Q, et al. International Journal of Biological Macromolecules, 2024, 277(1), 133843.

Nanostructured patches incorporating acyclovir (ACV) were designed for targeted antiviral therapy with enhanced drug release modulation. The trilayered patches were engineered using bacterial nanocellulose (BNC) membranes, hyaluronic acid (HA) as a skin-healing promoter, and glycerol (GLY) as a plasticizer and humectant. Two configurations were developed: ACVT, with acyclovir localized in the central layer, and ACVH, where acyclovir was distributed across two layers.
The patches were fabricated by diffusing ACV, hyaluronic acid (HA), and glycerol (GLY) into partially drained BNC membranes (~40% water content). Following complete absorption of the drug and excipients in acetate buffer (pH 5.5), the membranes were assembled into layered structures and dried at controlled conditions (28 °C, 24 hours). The final patches achieved a uniform ACV concentration of 0.27 mg/cm² across the layers, with glycerol serving as a plasticizer and humectant, and HA supporting skin regeneration. These nanostructured BNC patches represent a novel drug delivery platform that offers precise control over ACV release.

Martín-Bartolomé L, et al. European Journal of Pharmaceutical Sciences, 2024, 203, 106919.

Acyclovir (ACV), an antiviral agent, has been developed into a mucoadhesive vaginal tablet for the prolonged prevention of genital herpes. This innovative formulation combines advanced drug delivery technology with polymers to ensure controlled release and enhanced retention in the vaginal environment. The tablets were manufactured using a wet granulation process with ethanol as the wetting agent and polyvinylpyrrolidone (PVP) as the binder. Each tablet contains 100 mg of ACV, exceeding the inhibitory concentration to maintain therapeutic levels over several days. The polymer matrix, composed of chitosan, xanthan gum, and ethyl cellulose, was optimized to provide mucoadhesion and controlled drug release. Compression was performed using a hydraulic press, ensuring consistent shape and density.
Performance was evaluated in simulated vaginal fluid (pH 4.2) and a combined mixture of simulated seminal and vaginal fluids (pH 7.5) to replicate in vivo conditions before and after sexual intercourse. The formulation demonstrated prolonged ACV release and strong mucoadhesion, critical for maintaining antiviral efficacy in the vaginal environment.

Redín IL de, et al. Journal of Drug Delivery Science and Technology, 2024, 100, 106055.

A therapeutic bioadhesive gel (acyclovir-TBG) containing 5% acyclovir has been developed using Acyclovir to provide sustained antiviral activity and enhanced retention at the application site.
The gel is composed of a proprietary combination of polyvinylpyrrolidone (PVP), gelling agent (PC), glycerol (G), and propylene glycol (PG), alongside buffering and flavoring agents in a water-based system. The manufacturing process involves dissolving and dispersing components in two separate tanks with constant agitation, followed by homogenization and the gradual addition of gelling agents to produce a homogeneous and translucent gel. Temperature control (30-35 °C) ensures the integrity of acyclovir throughout production.
This acyclovir-TBG formulation represents a significant advancement in antiviral therapy by combining film-forming capabilities with sustained drug delivery, offering an innovative approach for localized and long-lasting treatment of viral infections.

Hagen T, et al. Cell Chemical Biology, 2024, 31(10), 1827-1838.

Acyclovir has been leveraged in the development of RNA nanodevices (RNs) that facilitate tunable, reversible, and non-toxic control of intracellular processes. This innovative application combines acyclovir's minimal cytotoxicity with aptamer technology to create a versatile platform for cellular modulation.
The modular RNA scaffold is built around a central F30 three-way junction, integrating an acyclovir aptamer on its input arm and an effector-binding aptamer on its output arm. This configuration enables rapid engineering of acyclovir-regulated RNA nanodevices. The system allows temporal and adjustable control over aptamers such as Broccoli, which fluoresces upon folding, and the iron-responsive element (IRE), which interacts with iron-regulatory proteins (IRPs).
Acyclovir-mediated regulation of IRE facilitates precise sequestration of IRPs, effectively inhibiting ferroptosis-a cell death pathway driven by iron-dependent lipid peroxidation. This mechanism underscores the potential of acyclovir to serve as a molecular switch, transforming aptamers into antagonists of physiologic target proteins.

Sezen S, et al. NeuroToxicology, 2025, 106, 1-9.

Acyclovir demonstrates significant neuroprotective potential in Parkinson's disease (PD) by mitigating 6-OHDA-induced neurotoxicity in SH-SY5Y cells. PD, a prevalent neurodegenerative disorder, is linked to oxidative stress and neuroinflammation via the kynurenine pathway, which produces the neurotoxin quinolinic acid (QUIN). QUIN exacerbates neuronal damage through nNOS activation and NMDA receptor-mediated excitotoxicity.
In Vitro studies revealed that acyclovir, at concentrations of 3.2-51.2 µM, significantly reduced 6-OHDA-induced cell mortality, oxidative stress, and neuroinflammation. Biochemical analysis showed reduced levels of IL-17A and total oxidative status (TOS), accompanied by increased total antioxidant capacity (TAC). Immunocytochemical findings highlighted decreased expressions of α-synuclein and TNF-α, markers of neuroinflammation and PD pathology.
In silico docking studies demonstrated that acyclovir interacts with key molecular targets, including TNF-α, IL-17A, IDO-1, nNOS, α-synuclein, and NMDA receptors. These interactions suggest its mechanism involves inhibiting QUIN synthesis and modulating neurotoxic pathways.These findings position acyclovir as a promising neuroprotective agent that modulates the kynurenine pathway, offering potential therapeutic value for PD by reducing oxidative stress and neuroinflammation in vitro.