Matrix-based controlled release delivery of acyclovir from poly-(ethylene co-vinyl acetate) rings

Abstract

Up to 85% of the US adult population carries herpes simplex virus type-1 (HSV-1), with a smaller percentage (22%) infected with HSV-2. Herpesviruses can survive in lytic phase, when the viruses are actively replicating, or in latency, when the virus is functionally dormant in ganglia. Among drugs to treat these infections is acyclovir (ACV). ACV exhibits poor oral bioavailability and a short in vivo half-life; only about 10-15% of ingested drug enters the bloodstream and its half-life is about 3 hours. With those disadvantages and the possibility of poor patient compliance, viral replication may not always be suppressed. To abrogate these shortcomings we propose local distribution via sustained drug release. We present a matrix-based antiherpetic ring, composed of poly(ethylene co-vinyl acetate), that releases ACV directly to the vaginal epithelium. A 30-day in vitro drug release trial showed that approximately 135 +/− 20 μg/day of ACV was consistently released. Rings were nontoxic in cell culture and suppressed primary HSV-1 and HSV-2 replication. We expect these data form the basis for novel interventions in human health, where new prophylactics and therapeutics against genital herpes are truly needed.

Instantaneous Inactivation of Herpes Simplex Virus by Silicon Nitride Bioceramics

“…To their disadvantage, burning sensations, itchiness, and dryness were side effects noted for zinc oxide/glycerin cream and zinc sulfate gel, respectively [ 136 ]. In a recently proposed approach, Giannasca et al [ 138 ] suggested a new approach to local distribution of acyclovir via sustained drug release through the incorporation of the antiviral agent into a polymeric matrix with the shape of an antiherpetic ring. This approach showed potential improvement with respect to the efficacy of the orally administered acyclovir drug and aimed at abrogating the two main shortcomings of oral dosing, namely, poor absorption by the gut and a rapid drop in plasma concentration (cf.…”

“…Applications could include the use of small fractional dispersions of Si 3 N 4 powder into indifferent creams, gels, and oral rinses (in substitution of zinc oxide and zinc sulfate) or its local exploitation via sustained hydrolytic release in polymeric matrix-based antiherpetic rings or mouthpieces. This latter approach is similar to that pursued by Giannasca et al [ 138 ], but it employs a solid-state antiviral compound rather than an absorbed drug incorporated in the polymeric matrix. Among the expected advantages, one could foresee high local effectiveness exactly at the location where herpes symptoms appear, easy maintenance, and strong prophylaxis with none of the shortcomings associated with oral uptake (e.g., poor absorption and renal metabolism of the drug before its reaching the target tissue).…”

The Vaginal Microbiota, Bacterial Biofilms and Polymeric Drug-Releasing Vaginal Rings

“…For the reservoir-type rings NuvaRing ® and Ornibel ® , the exterior membranes in contact with the vaginal mucosal tissue are EVA copolymers with 9% and 28% vinyl acetate, respectively. A number of experimental drug-releasing rings fabricated from EVA are also reported [8,18,[156][157][158][159][160][161][162][163][164][165].…”

“…Thermoplastic core-type VRs, such as the marketed products NuvaRing ® and Ornibel ® (Table 1), are prepared by hot melt co-extrusion. One extruder is used to compound the polymer and drug and a second extruder containing drug-free polymer is used to feed a co-extrusion die that simultaneously extrudes the active core coats in a drug-free polymer membrane [164,184,196]. With extrusion, the surface finish of the extrudate is influenced by several factors.…”

Pseudoboehmite as a drug delivery system for acyclovir

“…Sadat concluded [22] that there are different adsorption mechanisms for acyclovir on magnetite nanoparticles with different sizes. A matrix-based antiherpetic ring composed of poly(ethylene-co-vinyl acetate) was used to release acyclovir to the vaginal epithelium [25] and New strategies based on complex nanostructures for developing advanced functional materials providing sustained release acyclovir were published recently using coreshell nano ber [26] and sericin hydrogel [27].…”