Eur J Pharm Biopharm. 2003 Sep;56(2):183-7.
Increased efficacy of acyclovir-loaded microparticles against herpes simplex virus type 1 in cell culture.

de Jalon EG, Blanco-Prieto MJ, Ygartua P, Santoyo S.

Departamento de Farmacia y TecnologIa Farmaceutica, Universidad de Navarra, Pamplona, Spain.

Acyclovir is one of the most effective and selective agents against viruses of the herpes group. In order to increase its antiviral activity, acyclovir loaded microparticles, prepared by an O/W solvent evaporation method were developed. Their antiviral activity against herpes simplex virus type 1 (HSV-1) and toxicity were evaluated on Vero cells and then compared with those presented by a drug solution. The 50% inhibitory concentration (IC(50)) values for acyclovir loaded microspheres determined by plaque reduction assays at 48 and 96 h, were found to be 1.06 +/- 0.01 microM and 0.15 +/- 0.03 microM, respectively, while the equivalent values obtained for an acyclovir solution were 1.28 +/- 0.04 microM at 48 h and 0.27 +/- 0.02 microM at 96 h. These results indicate that acyclovir shows a higher antiviral activity, against herpes simplex virus type 1, when this drug was loaded in microparticles rather than as a drug solution, especially after 96 h of incubation. The toxicity of these microparticles was determined by the MTT test at 48 and 96 h. At 48 h only a small toxicity was found (cell viability ranged from 72 to 82%, with the higher concentration tested) and it could not be attributed to the microparticles, since the acyclovir control solution showed similar toxicity values. However, after 96 h a higher toxicity was observed with acyclovir microparticles as well as with the unloaded ones (cell viability located between 60 and 70%). In summary, acyclovir-loaded microparticles have shown to be promising carriers for the effective delivery of acyclovir in the treatment of HSV-1 infections in cells so they can have a potential use in vivo.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12957631&dopt=Abstract acyclovir Zovirax




Blood Cells Mol Dis. 2003 Sep-Oct;31(2):286-90.
Inhibition of sickling in vitro by three purine-based antiviral agents: an approach to the treatment of sickle cell disease.

DeBellis RH, Chen BX, Erlanger BF.

Department of Medicine, Columbia University, New York, NY 10032, USA.

As a result of an in vitro screening effort the antiviral agent acyclovir was found to inhibit aggregation of hemoglobin S and the sickling of erythrocytes from individuals with sickle cell disease. Sickling of the erythrocytes was significantly inhibited at 200 microg/ml under essentially anaerobic conditions, considerably more hypoxic than the conditions in which sickling occurs in sickle cell patients. The structurally related guanine-based antiviral agents ganciclovir, valacyclovir, and penciclovir were also tested. Valacyclovir and ganciclovir showed comparable anti-sickling activity at concentrations similar to that of acyclovir. An examination of the shared structural characteristics of the four guanine derivatives linked anti-sickling activity to the presence of an oxygen atom alpha to the N9 of the guanine moiety. These findings suggest a new approach in the search for new agents for the treatment of patients with sickle cell disease.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12972037&dopt=Abstract acyclovir Zovirax[PubMed - in process]




J Cutan Med Surg. 2003 Sep-Oct;7(5):372-81. Epub 2003 Sep 24.
Valacyclovir in the treatment of herpes simplex, herpes zoster, and other viral infections.

Wu JJ, Brentjens MH, Torres G, Yeung-Yue K, Lee P, Tyring SK.

Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA.

Background: Genital herpes and herpes labialis are prevalent, physically and pychologically painful, and often disabling. Herpes zoster is often very painful and may result in months or years of postherpetic neuralgia (PHN). Over the past two decades, the treatment of these conditions has been transformed by guanosine nucleoside antivirals such as valacyclovir (Valtrex((R))), a highly bioavailable prodrug of acyclovir (Zovirax((R))), and famciclovir (Famvir((R))), a highly bioavailable prodrug of penciclovir (Denavir((R))). Objective: We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections. Valacyclovir is also compared with acyclovir and famciclovir. Methods: All published literature containing the word "valacyclovir" was reviewed and summarized. Results: Valacyclovir is the only oral antiviral agent approved for therapy of herpes labialis, the only antiviral drug approved for a 3-day course in the episodic treatment of recurrent genital herpes, as well as the only antiviral drug approved for once daily dosing for suppressive therapy. In herpes zoster, valacyclovir is more effective than acyclovir and equally effective as famciclovir at hastening the healing of zoster-associated pain and PHN. Conclusion: Valacyclovir is safe and effective in the therapy of patients with herpes simplex and herpes zoster and may be useful in other viral infections.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14505192&dopt=Abstract acyclovir Zovirax[PubMed - in process]




Yao Xue Xue Bao. 2003 Jul;38(7):552-4.
[Preparation of acyclovir liposome and study on its stability]

[Article in Chinese]

Wu J, Zhu JB.

Zhongkun Pharmaceutical Institute, China Pharmaceutical University, Nanjing 210009, China.

AIM: To prepare acyclovir liposome for improvement the entrapment efficiency and stability. METHODS: Acyclovir liposome was prepared by the reverse evaporating method. Surfactants such as sodium deoxycholate and oleic acid were added to optimize the conditions and technology of preparing acyclovir liposome. The entrapment efficiency and particle size of the acyclovir liposome were determined. The liposome stability was proved by centrifugal acceleration experiment. RESULTS: The particle size of the acyclovir liposome was 219.8 nm with the polydispersity index of 0.158. The entrapment efficiency reached 65%. The liposome was stable. CONCLUSION: The results suggest that the conditions and technology are stable and practical to prepare the liposome with high entrapment efficient and stability.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14515805&dopt=Abstract acyclovir Zovirax[PubMed - in process]




Carbohydr Res. 2003 Oct 10;338(21):2185-93.
Synthesis and characterisation of sulfated amphiphilic alpha-, beta- and gamma-cyclodextrins: application to the complexation of acyclovir.

Dubes A, Degobert G, Fessi H, Parrot-Lopez H.

Laboratoire de Methodologies de Synthese et Molecules Bioactives, F-69622 Villeurbanne, France.

The synthesis of sulfated amphiphilic alpha-, beta- and gamma-cyclodextrins was achieved according to the standard protection-deprotection procedure. The formation of inclusion complexes between the amphiphilic alpha-, beta- and gamma-cyclodextrins and an antiviral molecule, acyclovir (ACV) was investigated by UV-visible spectroscopy (UV-Vis) and electrospray ionisation mass spectrometry (ESIMS). UV-Vis spectroscopy allowed determination of the stoichiometry and stability constants of complexes, whereas ESIMS, a soft ionisation technique, allowed the detection of the inclusion complexes. The results showed that the non-sulfated amphiphilic cyclodextrins exhibit a 1:2 stoichiometry with acyclovir, while sulfated amphiphilic cyclodextrins, except gamma-cyclodextrin, exhibit a 1:1 stoichiometry indicating the loss of one interaction site. Non-covalent interactions between acyclovir and non-sulfated amphiphilic cyclodextrins appear to take place both in the cavity of the cyclodextrin and inside the hydrophobic zone generated by alkanoyl chains. In contrast, in the case of sulfated amphiphilic cyclodextrins, the interactions appear to involve only the hydrophobic region of the alkanoyl chains.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14553979&dopt=Abstract acyclovir Zovirax[PubMed - in process]