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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Acyclovir in the Treatment of Herpes Viruses – A Review

Author(s): Katarzyna Kłysik, Aneta Pietraszek, Anna Karewicz and Maria Nowakowska*

Volume 27 , Issue 24 , 2020

Page: [4118 - 4137] Pages: 20

DOI: 10.2174/0929867325666180309105519

Price: $65


Background: Herpes Simplex (HSV) viruses are widely spread, highly contagious human pathogens. The statistics indicate that 50-90% of adults worldwide are seropositive for these viruses, mainly HSV-1 and HSV-2. The primary infection results in the appearance of watery blisters (cold sores) on the skin, lips, tongue, buccal mucosa or genitals. The ocular infection is the major cause of corneal blindness in the Western World. Once the HSV virus enters human body, it cannot be completely eradicated because HSV viruses are able to change into their latent form which can survive the treatment. The viron resides in trigeminal ganglia of the host, who becomes vulnerable to the reoccurrence of the disease during the whole lifespan. The neurotropic and neuro-invasive properties of HSV are responsible for neurodegenerative illnesses, such as Alzheimer's disease. Acyclovir and its analogues, being the inhibitors of the viral DNA replication, are the only approved medicines for HSV infection therapies.

Objective: The current paper presents the up-to-date overview of the important pharmacological features of acyclovir, its analogues and their delivery systems including the mechanism of action, routes of administration, absorption and metabolism, as well as side effects of the therapy.

Conclusion: Acyclovir remains the gold standard in the treatment of herpes virus infections, mainly due to the emerging of the new delivery systems improving considerably its bioavailability. The analogues of acyclovir, especially their esters, characterized by significantly higher bioavailability and safety, may gradually replace acyclovir in selected applications.

Keywords: Acyclovir, herpes simplex virus, acyclovir analogue, acyclovir ester, delivery system, route of administration, mechanism of action.

Tsatsos, M.; MacGregor, C.; Athanasiadis, I.; Moschos, M.M.; Hossain, P.; Anderson, D. Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents - response. Clin. Exp. Ophthalmol., 2017, 45(3), 317.
[] [PMID: 27635860]
Itzhaki, R.F.; Lin, W-R.; Shang, D.; Wilcock, G.K.; Faragher, B.; Jamieson, G.A. Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet, 1997, 349(9047), 241-244.
[] [PMID: 9014911]
Letenneur, L.; Pérès, K.; Fleury, H.; Garrigue, I.; Barberger-Gateau, P.; Helmer, C.; Orgogozo, J-M.; Gauthier, S.; Dartigues, J-F. Seropositivity to herpes simplex virus antibodies and risk of Alzheimer’s disease: a population-based cohort study. PLoS One, 2008, 3(11),e3637.
[] [PMID: 18982063]
Wozniak, M.A.; Frost, A.L.; Preston, C.M.; Itzhaki, R.F. Antivirals reduce the formation of key Alzheimer’s disease molecules in cell cultures acutely infected with herpes simplex virus type 1. PLoS One, 2011, 6(10),e25152.
[] [PMID: 22003387]
Piacentini, R.; De Chiara, G.; Puma, D.D.Li.; Ripoli, C.; Marcocci, M.E.; Garaci, E.; Palamara, A.T.; Grassi, C. HSV-1 and Alzheimer’s disease: more than a hypothesis. Front Pharmacol., 2014, 5, 97.
[] [PMID: 24847267]
Harris, S.A.; Harris, E.A. Herpes simplex virus type 1 and other pathogens are key causative factors in sporadic alzheimer’s disease. J. Alzheimers Dis., 2015, 48(2), 319-353.
[] [PMID: 26401998]
Tumpang, M.A.; Ramli, N.A.; Hussain, Z. Phytomedicines are efficient complementary therapies for the treatment of atopic dermatitis: A review of mechanistic insight and recent updates. Curr. Drug Targets, 2018, 19(6), 674-700.
[] [PMID: 28914203]
Wu, Y.H.; Zhang, B.Y.; Qiu, L.P.; Guan, R.F.; Ye, Z.H.; Yu, X.P. Structure properties and mechanisms of action of naturally originated phenolic acids and their derivatives against human viral infections. Curr. Med. Chem., 2017, 24(38), 4279-4302.
[] [PMID: 28814240]
Alauddin, M.M. Journey of 2′-deoxy-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU): from Antiviral Drug to PET Imaging Agent. Curr. Med. Chem., 2018, 25(16), 1867-1878.
[] [PMID: 29189119]
Savoia, P.; Ranghino, A.; Fava, P. Characterization and management of cutaneous side effects related to the immunosuppressive treatment in solid organ recipients. Curr. Drug Targets, 2017, 18(4), 436-446.
[] [PMID: 26758664]
Szczubiałka, K.; Pyrć, K.; Nowakowska, M. In search for effective and definitive treatment of herpes simplex virus type 1 (HSV-1) infections. RSC Advances, 2016, 6(2), 1058-1075.
Engel, J.P.; Englund, J.A.; Fletcher, C.V.; Hill, E.L. Treatment of resistant herpes simplex virus with continuous-infusion acyclovir. JAMA, 1990, 263(12), 1662-1664.
[] [PMID: 2308204]
Holcakova, J.; Tomasec, P.; Bugert, J.J.; Wang, E.C.; Wilkinson, G.W.; Hrstka, R.; Krystof, V.; Strnad, M.; Vojtesek, B. The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties. Antivir. Chem. Chemother., 2010, 20(3), 133-142.
[] [PMID: 20054100]
Leung, D.T.; Sacks, S.L. Current recommendations for the treatment of genital herpes. Drugs, 2000, 60(6), 1329-1352.
[] [PMID: 11152015]
De Clercq, E. Antiviral drugs in current clinical use. J. Clin. Virol., 2004, 30(2), 115-133.
[] [PMID: 15125867]
dos Santos, D.M.; Canduri, F.; Pereira, J.H.; Vinicius Bertacine Dias, M.; Silva, R.G.; Mendes, M.A.; Palma, M.S.; Basso, L.A.; de Azevedo, W.F., Jr; Santos, D.S. Crystal structure of human purine nucleoside phosphorylase complexed with acyclovir. Biochem. Biophys. Res. Commun., 2003, 308(3), 553-559.
[] [PMID: 12914786]
Canduri, F.; Fadel, V.; Basso, L.A.; Palma, M.S.; Santos, D.S.; de Azevedo, W.F., Jr New catalytic mechanism for human purine nucleoside phosphorylase. Biochem. Biophys. Res. Commun., 2005, 327(3), 646-649.
[] [PMID: 15649395]
De Clercq, E.; Field, H.J. Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapy. Br. J. Pharmacol., 2006, 147(1), 1-11.
[] [PMID: 16284630]
Elion, G.B.; Furman, P.A.; Fyfe, J.A.; de Miranda, P.; Beauchamp, L.; Schaeffer, H.J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc. Natl. Acad. Sci. USA, 1977, 74(12), 5716-5720.
[] [PMID: 202961]
Snejdrova, E.; Drastik, M.; Dittrich, M.; Kastner, P.; Nguyenova, J. Mucoadhesive plasticized system of branched poly(lactic-co-glycolic acid) with aciclovir. Drug Dev. Ind. Pharm., 2016, 42(10), 1653-1659.
[] [PMID: 26925606]
Ates, M.; Kaynak, M.S.; Sahin, S. Effect of permeability enhancers on paracellular permeability of acyclovir. J. Pharm. Pharmacol., 2016, 68(6), 781-790.
[] [PMID: 27061718]
Snoeck, R.; Andrei, G.; De Clercq, E. Current pharmacological approaches to the therapy of varicella zoster virus infections: a guide to treatment. Drugs, 1999, 57(2), 187-206.
[] [PMID: 10188760]
Keam, S.J.; Chapman, T.M.; Figgitt, D.P. Brivudin (bromovinyl deoxyuridine). Drugs, 2004, 64(18), 2091-2097.
[] [PMID: 15341504]
O’Brien, J.J.; Campoli-Richards, D.M. Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs, 1989, 37(3), 233-309.
[PMID: 2653790]
Wagstaff, A.J.; Faulds, D.; Goa, K.L. Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs, 1994, 47(1), 153-205.
[] [PMID: 7510619]
Hebart, H.; Kanz, L.; Jahn, G.; Einsele, H. Management of cytomegalovirus infection after solid-organ or stem-cell transplantation. Current guidelines and future prospects. Drugs, 1998, 55(1), 59-72.
[] [PMID: 9463790]
Slifkin, M.; Doron, S.; Snydman, D.R. Viral prophylaxis in organ transplant patients. Drugs, 2004, 64(24), 2763-2792.
[] [PMID: 15563248]
Bhosale, U.; Kusum, D.V.; Jain, N. Formulation and optimization of mucoadhesive nanodrug delivery system of acyclovir. J. Young Pharm., 2011, 3(4), 275-283.
[] [PMID: 22224033]
Elion, G.B. Acyclovir: discovery, mechanism of action, and selectivity. J. Med. Virol., 1993(Suppl. 1), 2-6.
[] [PMID: 8245887]
Shahsavari, S.; Vasheghani-Farahani, E.; Ardjmand, M.; Abedin Dorkoosh, F. Design and characterization of acyclovir loaded nanoparticles for controlled delivery system. Curr. Nanosci., 2014, 10(4), 521-531.
Ramyadevi, D.; Rajan, K.S. Synthesis of hybrid polymer blend nanoparticles and incorporation into in situ gel foam spray for controlled release therapy using a versatile synthetic purine nucleoside analogue antiviral drug. RSC Advances, 2015, 5(17), 12956-12973.
Ajima, U.; Onah, J.O. Spectrophotometric determination of acyclovir after its reaction with ninhydrin and ascorbic acid. J. Appl. Sci.,, 2015, 5(4), 065-069.
Sultan, M. Spectrophotometric determination of acyclovir in some pharmaceutical formulations. Farmaco, 2002, 57(11), 865-870.
[] [PMID: 12484534]
Gonzalez, M.H.; Silva, C.S.d.; Amaral, C.D.; Bianchi, S.R.; de Oliveira, L.H.; Coelho, J.S.; Oliveira, A.; Nogueira, A.R.A. Determination of elemental impurities in acyclovir ointment and raw materials using microwave acid digestion (MW-AD) and ICP-MS. J. Braz. Chem. Soc., 2017, 28(1), 98-105.
Darwish, I.A.; Khedr, A.S.; Askal, H.F.; Mahmoud, R.M. Simple fluorimetric method for determination of certain antiviral drugs via their oxidation with cerium (IV). Farmaco, 2005, 60(6-7), 555-562.
[] [PMID: 15932755]
Darwish, I.A.; Khedr, A.S.; Askal, H.F.; Mahmoud, R.M.; Liu, B.; Liu, Z.; Gao, J.; Cao, Z.; Ali, S.; Shahzadi, S. Use of oxidation reactions for the spectrophotometric determination of acyclovir and amantadine hydrochloride in their dosage forms. Analytical Chemistry: An Indian Journal,, 2005, 1(1-2), 01-09.
El-Din, M.K.; El-Brashy, A.M.; Sheribah, Z.A.; El-Gamal, R.M. Spectrophotometric determination of acyclovir and ribavirin in their dosage forms. J. AOAC Int., 2006, 89(3), 631-641.
[] [PMID: 16792062]
Reddy, S.A.; Chakraborty, R.; Sen, S.; Parameshappa, B. Spectrophotometric determination and validation of Acyclovir. Arch. Appl. Sci. Res., 2011, 3(1), 328-332.
Dongare, U.S.; Chemate, S.Z.; Jadhav, S.A.; Pawar, V.R. Spectrophotometric determination and validation of acyclovir in tablet dosage form. Int. J. Pharm. Tech. Res., 2012, 4(4), 1840-1845.
Darville, J.M.; Lovering, A.M.; MacGowan, A.P. Development, evaluation and application of an isocratic high-performance liquid chromatography (HPLC) assay for the simultaneous determination of aciclovir and its metabolite 9-carboxymethoxymethylguanine in human serum and cerebrospinal fluid. Int. J. Antimicrob. Agents, 2007, 30(1), 30-33.
[] [PMID: 17428641]
Bahrami, G.; Mirzaeei, Sh.; Kiani, A. Determination of acyclovir in human serum by high-performance liquid chromatography using liquid-liquid extraction and its application in pharmacokinetic studies. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2005, 816(1-2), 327-331.
[] [PMID: 15664366]
Maes, A.; Garré, B.; Desmet, N.; van der Meulen, K.; Nauwynck, H.; De Backer, P.; Croubels, S. Determination of acyclovir in horse plasma and body fluids by high-performance liquid chromatography combined with fluorescence detection and heated electrospray ionization tandem mass spectrometry. Biomed. Chromatogr., 2009, 23(2), 132-140.
[] [PMID: 18823074]
Muralidharan, S.; Kalaimani, J.; Parasuraman, S.; Dhanaraj, S.A. Development and validation of acyclovir HPLC external standard method in human plasma: application to pharmacokinetic studies. Adv. Pharm., 2014, 2014
Emami, J.; Bazargan, N.; Ajami, A. HPLC determination of acyclovir in human serum and its application in bioavailability studies. Res. Pharm. Sci., 2010, 4(1), 47-54.
Al-Amri, K.A.; Mohsin, K.; Alanazi, F.K. Development and validation of a UPLC method for quantification of antiviral agent, Acyclovir in lipid-based formulations. Arab. J. Chem., 2019, 12(7), 1707-1714.
Vo, H.C.; Henning, P.A.; Leung, D.T.; Sacks, S.L. Development and validation of a plasma assay for acyclovir using high-performance capillary electrophoresis with sample stacking. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2002, 772(2), 291-297.
[] [PMID: 12007774]
Zhang, S.; Yuan, Z.; Liu, H.; Zou, H.; Xiong, H.; Wu, Y. Analysis of acyclovir by high performance capillary electrophoresis with on-column amperometric detection. Electrophoresis,, 2000, 21( 14), 2995- 2998.
[ <2995:AID-ELPS2995>3.0.CO;2-P] [PMID: 11001315]
Meyer, L.J.; de Miranda, P.; Sheth, N.; Spruance, S. Acyclovir in human breast milk. Am. J. Obstet. Gynecol., 1988, 158(3 Pt 1), 586-588.
[] [PMID: 3348321]
Tod, M.; Lokiec, F.; Bidault, R.; De Bony, F.; Petitjean, O.; Aujard, Y. Pharmacokinetics of oral acyclovir in neonates and in infants: a population analysis. Antimicrob. Agents Chemother., 2001, 45(1), 150-157.
[] [PMID: 11120958]
Dilgin, D.G.; Karakaya, S. Differential pulse voltammetric determination of acyclovir in pharmaceutical preparations using a pencil graphite electrode. Mater. Sci. Eng. C, 2016, 63, 570-576.
[] [PMID: 27040252]
Castro, A.A.; Cordoves, A.I.; Farias, P.A. Determination of the antiretroviral drug acyclovir in diluted alkaline electrolyte by adsorptive stripping voltammetry at the mercury film electrode. Anal. Chem. Insights, 2013, 8, 21-28.
[] [PMID: 23761958]
Shaidarova, L.; Gedmina, A.; Zhaldak, E.; Chelnokova, I.; Budnikov, H. Voltammetric determination of acyclovir in drugs using an electrode modified by ruthenium hexachloroplatinate or hexacyanocobaltate film. Pharm. Chem. J., 2015, 48(11), 747-752.
Sheribah, Z.A.; El-Brashy, A.M.; El-Gamal, R.M. Stability-indicating polarographic determination of acyclovir through chelation with nickel(II). J. AOAC Int., 2009, 92(2), 419-427.
[PMID: 19485200]
Shetti, N.P.; Malode, S.J.; Nandibewoor, S.T. Electrochemical behavior of an antiviral drug acyclovir at fullerene-C(60)-modified glassy carbon electrode. Bioelectrochemistry, 2012, 88, 76-83.
[] [PMID: 22796504]
Steingrimsdottir, H.; Gruber, A.; Palm, C.; Grimfors, G.; Kalin, M.; Eksborg, S. Bioavailability of aciclovir after oral administration of aciclovir and its prodrug valaciclovir to patients with leukopenia after chemotherapy. Antimicrob. Agents Chemother., 2000, 44(1), 207-209.
[] [PMID: 10602752]
Tran, T.; Druce, J.D.; Catton, M.C.; Kelly, H.; Birch, C.J. Changing epidemiology of genital herpes simplex virus infection in Melbourne, Australia, between 1980 and 2003. Sex. Transm. Infect., 2004, 80(4), 277-279.
[] [PMID: 15295125]
Emmert, D.H. Treatment of common cutaneous herpes simplex virus infections. Am Fam Physician, , 2000, 61(6), 1697-1706-1708..
Rossi, S.; Sandri, G.; Ferrari, F.; Bonferoni, M.C.; Caramella, C. Buccal delivery of acyclovir from films based on chitosan and polyacrylic acid. Pharm. Dev. Technol., 2003, 8(2), 199-208.
[] [PMID: 12760570]
de Miranda, P.; Whitley, R.J.; Blum, M.R.; Keeney, R.E.; Barton, N.; Cocchetto, D.M.; Good, S.; Hemstreet, G.P., III; Kirk, L.E.; Page, D.A.; Elion, G.B. Acyclovir kinetics after intravenous infusion. Clin. Pharmacol. Ther., 1979, 26(6), 718-728.
[] [PMID: 227639]
Xu, Y.; Yuan, Z.; Ni, B.J. Biotransformation of acyclovir by an enriched nitrifying culture. Chemosphere, 2017, 170, 25-32.
[] [PMID: 27974268]
Rossi, S. Australian Medicines Handbook (2013 ed.);The Australian Medicines Handbook Unit Trust: Adelaide , 2013.
Chiriac, A.; Chiriac, A.E.; Pinteala, T.; Moldovan, C.; Stolnicu, S. Allergic contact dermatitis from topical acyclovir: case series. J. Emerg. Med., 2017, 52(2), e37-e39.
[] [PMID: 27658557]
Yorulmaz, A.; Sahin, E.B.; Sener, M.; Kulcu Cakmak, S. Acyclovir-induced bullous reaction in a patient with metastatic breast cancer. Cutan. Ocul. Toxicol., 2017, 36(1), 85-87.
[] [PMID: 26911608]
Stein, D.S.; Graham, N.M.; Park, L.P.; Hoover, D.R.; Phair, J.P.; Detels, R.; Ho, M.; Saah, A.J. The effect of the interaction of acyclovir with zidovudine on progression to AIDS and survival. Analysis of data in the Multicenter AIDS Cohort Study. Ann. Intern. Med., 1994, 121(2), 100-108.
[] [PMID: 8017721]
Bach, M.C. Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS. N. Engl. J. Med., 1987, 316(9), 547.
[] [PMID: 3468354]
Pottage, J.C., Jr; Kessler, H.A.; Goodrich, J.M.; Chase, R.; Benson, C.A.; Kapell, K.; Levin, S. In vitro activity of ketoconazole against herpes simplex virus. Antimicrob. Agents Chemother., 1986, 30(2), 215-219.
[] [PMID: 3021048]
Laskin, O.L.; de Miranda, P.; King, D.H.; Page, D.A.; Longstreth, J.A.; Rocco, L.; Lietman, P.S. Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans. Antimicrob. Agents Chemother., 1982, 21(5), 804-807.
[] [PMID: 7103460]
Plosker, G.L. Emtricitabine/tenofovir disoproxil fumarate: a review of its use in HIV-1 pre-exposure prophylaxis. Drugs, 2013, 73(3), 279-291.
[] [PMID: 23444256]
Levin, M.J.; Leary, P.L. Inhibition of human herpesviruses by combination of acyclovir and human leukocyte interferon. Infect. Immun., 1981, 32(3), 995-999.
[] [PMID: 6166569]
Dzieciatkowski, T.; Rola, A.; Majewska, A.; Solarska, M.; Luczak, M. Leki stosowane w leczeniu zakazen herpeswirusami ludzi. Postepy Mikrobiol., 2007, 3(46), 211-221.
Datta, A.K.; Colby, B.M.; Shaw, J.E.; Pagano, J.S. Acyclovir inhibition of Epstein-Barr virus replication. Proc. Natl. Acad. Sci. USA, 1980, 77(9), 5163-5166.
[] [PMID: 6254061]
Boulter, E.A.; Thornton, B.; Bauer, D.J.; Bye, A. Successful treatment of experimental B virus (Herpesvirus simiae) infection with acyclovir. BMJ, 1980, 280(6215), 681-683.
[] [PMID: 6244873]
Styczynski, J.; Reusser, P.; Einsele, H.; de la Camara, R.; Cordonnier, C.; Ward, K.N.; Ljungman, P.; Engelhard, D.; Leukemia, S.E.C.I.i. Second European Conference on Infections in Leukemia. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant., 2009, 43(10), 757-770.
[] [PMID: 19043458]
Selby, P.J.; Powles, R.L.; Janeson, B.; Kay, H.E.; Watson, J.G.; Thornton, R.; Morgenstern, G.; Clink, H.M.; McElwain, T.J.; Prentice, H.G.; Corringharn, R.; Ross, M.G.; Hoffbrand, A.V.; Brigden, D. Parenteral acyclovir therapy for herpesvirus infections in man. Lancet,, 1979,, 2(8155), 1267-1270.
[] [PMID: 93183]
Przybylski, M.; Majewska, A.; Dzieciatkowski, T.; Rusicka, P.; Basak, G.W.; Nasilowska-Adamska, B.; Bilinski, J.; Jedrzejczak, W.W.; Wroblewska, M.; Halaburda, K.; Mlynarczyk, G.; Tomaszewska, A. Infections due to alphaherpesviruses in early post-transplant period after allogeneic haematopoietic stem cell transplantation: Results of a 5-year survey. J. Clin. Virol., 2017, 87, 67-72.
[] [PMID: 28033514]
O’Meara, A.; Hillary, I.B. Acyclovir in the management of herpes virus infections in immunosuppressed children. Ir. J. Med. Sci., 1981, 150(3), 73-77.
[] [PMID: 6262272]
O’Meara, A.; Deasy, P.F.; Hillary, I.B.; Bridgen, W.D. Acyclovir for treatment of mucocutaneous herpes infection in a child with leukaemia. Lancet,, 1979,, 2(8153), , 1196..
[] [PMID: 91931]
de Almeida, S.M.; Crippa, A.; Cruz, C.; de Paola, L.; de Souza, L.P.; Noronha, L.; Torres, L.F.; Koneski, J.A.; Pessa, L.F.; Nogueira, M.B.; Raboni, S.M.; Silvado, C.E.; Vidal, L.R. Reactivation of herpes simplex virus-1 following epilepsy surgery. Epilepsy Behav. Case Rep., 2015, 4, 76-78.
[] [PMID: 26543809]
Sicher, S.E.; Oh, J.O. Acyclovir therapy of neonatal herpes simplex virus type 2 infections in rabbits. Antimicrob. Agents Chemother., 1981, 20(4), 503-507.
[] [PMID: 6282195]
Sacks, S.L. The role of oral acyclovir in the management of genital herpes simplex. CMAJ, 1987, 136(7), 701-707.
[PMID: 3548933]
Wilhelmus, K.R.; Coster, D.J.; Jones, B.R. Acyclovir and debridement in the treatment of ulcerative herpetic keratitis. Am. J. Ophthalmol., 1981, 91(3), 323-327.
[] [PMID: 7011037]
Coster, D.J.; Wilhelmus, K.R.; Michaud, R.; Jones, B.R. A comparison of acyclovir and idoxuridine as treatment for ulcerative herpetic keratitis. Br. J. Ophthalmol., 1980, 64(10), 763-765.
[] [PMID: 7000170]
Bagwell, A.; Loy, A.; McFarland, M.S.; Tessmer-Neubauer, A. oral acyclovir in the treatment of verruca. J. Drugs Dermatol., 2016, 15(2), 237-238.
[PMID: 26885794]
Carter, S.B.; Cohen, E.J. Development of herpes simplex virus infectious epithelial keratitis during oral acyclovir therapy and response to topical antivirals. Cornea, 2016, 35(5), 692-695.
[] [PMID: 26989961]
Piret, J.; Désormeaux, A.; Gourde, P.; Juhász, J.; Bergeron, M.G. Efficacies of topical formulations of foscarnet and acyclovir and of 5-percent acyclovir ointment (Zovirax) in a murine model of cutaneous herpes simplex virus type 1 infection. Antimicrob. Agents Chemother., 2000, 44(1), 30-38.
[] [PMID: 10602719]
Studahl, M.; Lindquist, L.; Eriksson, B-M.; Günther, G.; Bengner, M.; Franzen-Röhl, E.; Fohlman, J.; Bergström, T.; Aurelius, E. Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management. Drugs, 2013, 73(2), 131-158.
[] [PMID: 23377760]
Frobert, E.; Ooka, T.; Cortay, J.C.; Lina, B.; Thouvenot, D.; Morfin, F. Herpes simplex virus thymidine kinase mutations associated with resistance to acyclovir: a site-directed mutagenesis study. Antimicrob. Agents Chemother., 2005, 49(3), 1055-1059.
[] [PMID: 15728902]
Gilbert, C.; Bestman-Smith, J.; Boivin, G. Resistance of herpesviruses to antiviral drugs: clinical impacts and molecular mechanisms. Drug Resist. Updat., 2002, 5(2), 88-114.
[] [PMID: 12135584]
Hwang, C.B.; Ruffner, K.L.; Coen, D.M. A point mutation within a distinct conserved region of the herpes simplex virus DNA polymerase gene confers drug resistance. J. Virol., 1992, 66(3), 1774-1776.
[] [PMID: 1310779]
Bergmann,, M.; Beer, R.; Kofler, M.; Helbok, R.; Pfausler, B.; Schmutzhard, E. Acyclovir resistance in herpes simplex virus type I encephalitis: a case report. J. Neurovirol., 2017, 23(4), 638-639.
[] [PMID: 27787806]
Jones, C.A. Vertical transmission of genital herpes: prevention and treatment options. Drugs, 2009, 69(4), 421-434.
[] [PMID: 19323586]
Kanneti, R.; Bhavesh, D.; Paramar, D.; Shivaprakash, R.; Bhatt, P.A. Determination of penciclovir in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry: application to a clinical pharmacokinetic study. Biomed. Chromatogr., 2011, 25(4), 458-465.
[] [PMID: 21374647]
Kimberlin, D.W. Acyclovir derivatives and other new antiviral agents in: Seminars in Pediatric Infectious Diseases; Elsevier, 2001, Vol. 12, pp. 224-234.
Snell, N.J. New treatments for viral respiratory tract infections--opportunities and problems. J. Antimicrob. Chemother., 2001, 47(3), 251-259.
[] [PMID: 11222557]
Deval, J. Antimicrobial strategies: inhibition of viral polymerases by 3′-hydroxyl nucleosides. Drugs, 2009, 69(2), 151-166.
[] [PMID: 19228073]
Moomaw, M.D.; Cornea, P.; Rathbun, R.C.; Wendel, K.A. Review of antiviral therapy for herpes labialis, genital herpes and herpes zoster. Expert Rev. Anti Infect. Ther., 2003, 1(2), 283-295.
[] [PMID: 15482124]
Smee, D.F.; Martin, J.C.; Verheyden, J.P.; Matthews, T.R. Anti-herpesvirus activity of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine. Antimicrob. Agents Chemother., 1983, 23(5), 676-682.
[] [PMID: 6307132]
Mitsuiki, N.; Tamanuki, K.; Sei, K.; Ito, J.; Kishi, A.; Kobayashi, K.; Hatai, Y.; Nagasawa, M. Severe neonatal CMV infection complicated with thrombotic microangiopathy successfully treated with ganciclovir. J. Infect. Chemother., 2017, 23(2), 107-110.
[] [PMID: 27627852]
Wagner, S.J.; Brennan, D.C. Induction therapy in renal transplant recipients: how convincing is the current evidence? Drugs, 2012, 72(5), 671-683.
[] [PMID: 22439670]
Tabbara, K.F.; Al Balushi, N. Topical ganciclovir in the treatment of acute herpetic keratitis. Clin. Ophthalmol., 2010, 4(1), 905-912.
[] [PMID: 20823931]
Wong, J.X.; Agrawal, R.; Wong, E.P.; Teoh, S.C. Efficacy and safety of topical ganciclovir in the management of cytomegalovirus (CMV)-related anterior uveitis. J. Ophthalmic Inflamm. Infect., 2016, 6(1), 10.
[] [PMID: 26976016]
Markham, A.; Faulds, D. Ganciclovir. An update of its therapeutic use in cytomegalovirus infection. Drugs, 1994, 48(3), 455-484.
[] [PMID: 7527763]
Friedrichsen, G.M.; Chen, W.; Begtrup, M.; Lee, C-P.; Smith, P.L.; Borchardt, R.T. Synthesis of analogs of L-valacyclovir and determination of their substrate activity for the oligopeptide transporter in Caco-2 cells. Eur. J. Pharm. Sci., 2002, 16(1-2), 1-13.
[] [PMID: 12113886]
Morfin, F.; Thouvenot, D. Herpes simplex virus resistance to antiviral drugs. J. Clin. Virol., 2003, 26(1), 29-37.
[] [PMID: 12589832]
Skevaki, C.L.; Galani, I.E.; Pararas, M.V.; Giannopoulou, K.P.; Tsakris, A. Treatment of viral conjunctivitis with antiviral drugs. Drugs, 2011, 71(3), 331-347.
[] [PMID: 21319870]
Brantley, J.S.; Hicks, L.; Sra, K.; Tyring, S.K. Valacyclovir for the treatment of genital herpes. Expert Rev. Anti Infect. Ther., 2006, 4(3), 367-376.
[] [PMID: 16771614]
Corey, L. Challenges in genital herpes simplex virus management. J. Infect. Dis., 2002, 186(Suppl. 1), S29-S33.
[] [PMID: 12353184]
Naesens, L.; De Clercq, E. Recent developments in herpesvirus therapy. Herpes, 2001, 8(1), 12-16.
[PMID: 11867011]
Whitley, R. New approaches to the therapy of HSV infections. Herpes, 2006, 13(2), 53-55.
[PMID: 16895657]
Wiltshire, H.; Hirankarn, S.; Farrell, C.; Paya, C.; Pescovitz, M.D.; Humar, A.; Dominguez, E.; Washburn, K.; Blumberg, E.; Alexander, B.; Freeman, R.; Heaton, N. Valganciclovir Solid Organ Transplant Study Group. Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients. Clin. Pharmacokinet., 2005, 44(5), 495-507.
[] [PMID: 15871635]
Pereyra, F.; Rubin, R.H. Prevention and treatment of cytomegalovirus infection in solid organ transplant recipients. Curr. Opin. Infect. Dis., 2004, 17(4), 357-361.
[] [PMID: 15241082]
Qureshi, S.A.; Jiang, M.; Midha, K.K.; Skelly, J.P. In vitro evaluation of percutaneous absorption of an acyclovir product using intact and tape-stripped human skin. J. Pharm. Pharm. Sci., 1998, 1(3), 102-107.
[PMID: 10948397]
Shojaei, A.H.; Berner, B.; Xiaoling, L. Transbuccal delivery of acyclovir: I. In vitro determination of routes of buccal transport. Pharm. Res., 1998, 15(8), 1182-1188.
[] [PMID: 9706047]
Susantakumar, P.; Gaur, A.; Sharma, P. Comparative pharmacokinetics, safety and tolerability evaluation of Acyclovir IR 800 mg tablet in healthy Indian adult volunteers under fasting and non-fasting conditions. J. Bioequivalence Bioavailab., 2011, 3, 128-138.
Calderón, L.; Harris, R.; Cordoba-Diaz, M.; Elorza, M.; Elorza, B.; Lenoir, J.; Adriaens, E.; Remon, J.P.; Heras, A.; Cordoba-Diaz, D. Nano and microparticulate chitosan-based systems for antiviral topical delivery. Eur. J. Pharm. Sci., 2013, 48(1-2), 216-222.
[] [PMID: 23159663]
Cortesi, R.; Esposito, E. Acyclovir delivery systems. Expert Opin. Drug Deliv., 2008, 5(11), 1217-1230.
[] [PMID: 18976132]
Fresta, M.; Fontana, G.; Bucolo, C.; Cavallaro, G.; Giammona, G.; Puglisi, G. Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir. J. Pharm. Sci., 2001, 90(3), 288-297.
[<288:AID-JPS4>3.0.CO;2-5] [PMID: 11170022]
Godin, B.; Touitou, E. Ethosomes: new prospects in transdermal delivery. Crit. Rev. Ther. Drug Carrier Syst., 2003, 20(1), 63-102.
[] [PMID: 12911264]
Zhou, Y.; Wei, Y-H.; Zhang, G-Q.; Wu, X-A. Synergistic penetration of ethosomes and lipophilic prodrug on the transdermal delivery of acyclovir. Arch. Pharm. Res., 2010, 33(4), 567-574.
[] [PMID: 20422366]
Giammona, G.; Puglisi, G.; Cavallaro, G.; Spadaro, A.; Pitarresi, G. Chemical stability and bioavailability of acyclovir coupled to α, β-poly (N-2-hydroxyethyl)-dl-aspartamide. J. Control. Release, 1995, 33(2), 261-271.
Hiramath, R.; Chandrashakhar, M.; Sompur, C.; Shattari, A.; Maske, A.; Shaikh, R. Synthesis, in-vitro and bio-availability studies of acyclovir prodrug. AJPSR, 2011, 1(1), 38-48.
Sawdon, A.J.; Peng, C.A. Polymeric micelles for acyclovir drug delivery. Colloids Surf. B Biointerfaces, 2014, 122, 738-745.
[] [PMID: 25193154]
Pedotti, S.; Pistarà, V.; Cannavà, C.; Carbone, C.; Cilurzo, F.; Corsaro, A.; Puglisi, G.; Ventura, C.A. Synthesis and physico-chemical characterization of a β-cyclodextrin conjugate for sustained release of Acyclovir. Carbohydr. Polym., 2015, 131, 159-167.
[] [PMID: 26256172]
Wolinsky, J.B.; Colson, Y.L.; Grinstaff, M.W. Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers. J. Control. Release, 2012, 159(1), 14-26.
[] [PMID: 22154931]
Lembo, D.; Swaminathan, S.; Donalisio, M.; Civra, A.; Pastero, L.; Aquilano, D.; Vavia, P.; Trotta, F.; Cavalli, R. Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent’s antiviral efficacy. Int. J. Pharm., 2013, 443(1-2), 262-272.
[] [PMID: 23279938]
Malik, N.S.; Ahmad, M.; Minhas, M.U. Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir. PLoS One, 2017, 12(2),e0172727.
[] [PMID: 28245257]
Jana, S.; Sharma, R.; Maiti, S.; Sen, K.K. Interpenetrating hydrogels of O-carboxymethyl Tamarind gum and alginate for monitoring delivery of acyclovir. Int. J. Biol. Macromol., 2016, 92, 1034-1039.
[] [PMID: 27514441]
Azizi, M.; Seyed Dorraji, M.S.; Rasoulifard, M.H. Influence of structure on release profile of acyclovir loaded polyurethane nanofibers: Monolithic and core/shell structures. J. Appl. Polym. Sci., 2016, 133(41)
Wu, Y.-H.; Yu, D.-G.; Li, H.-P.; Wu, X.-Y.; Li, X.-Y. Medicated structural PVP/PEG composites fabricated using coaxial electrospinning. e-Polymers,, 2017,, 17(1), 39-44.
Tamayo, A.; Mazo, M.A.; Ruiz-Caro, R.; Martín-Illana, A.; Bedoya, L.M.; Veiga-Ochoa, M.D.; Rubio, J. Mesoporous silicon oxycarbide materials for controlled drug delivery systems. Chem. Eng. J., 2015, 280, 165-174.
Maniya, N.H.; Patel, S.R.; Murthy, Z. Controlled delivery of acyclovir from porous silicon micro-and nanoparticles. Appl. Surf. Sci., 2015, 330, 358-365.
Jain, N.; Rajoriya, V.; Jain, P.K.; Jain, A.K. Lactosaminated-N-succinyl chitosan nanoparticles for hepatocyte-targeted delivery of acyclovir. J. Nanopart. Res., 2014, 16(1), 2136.
Yao, J.; Zhang, Y.; Ramishetti, S.; Wang, Y.; Huang, L. Turning an antiviral into an anticancer drug: nanoparticle delivery of acyclovir monophosphate. J. Control. Release, 2013, 170(3), 414-420.
[] [PMID: 23791977]
Anand, B.S.; Mitra, A.K. Mechanism of corneal permeation of L-valyl ester of acyclovir: targeting the oligopeptide transporter on the rabbit cornea. Pharm. Res., 2002, 19(8), 1194-1202.
[] [PMID: 12240946]
Canbolat, M.F.; Celebioglu, A.; Uyar, T. Drug delivery system based on cyclodextrin-naproxen inclusion complex incorporated in electrospun polycaprolactone nanofibers. Colloids Surf. B Biointerfaces, 2014, 115, 15-21.
[] [PMID: 24316584]
Zhang, Y.; Zhang, J.; Jiang, T.; Wang, S. Inclusion of the poorly water-soluble drug simvastatin in mesocellular foam nanoparticles: drug loading and release properties. Int. J. Pharm., 2011, 410(1-2), 118-124.
[] [PMID: 20674729]
Hung, S.F.; Hsieh, C.M.; Chen, Y.C.; Wang, Y.C.; Ho, H.O.; Sheu, M.T. Characterizations of plasticized polymeric film coatings for preparing multiple-unit floating drug delivery systems (muFDDSs) with controlled-release characteristics. PLoS One, 2014, 9(6),e100321.
[] [PMID: 24967594]
Ghosh, P.K.; Majithiya, R.J.; Umrethia, M.L.; Murthy, R.S. Design and development of microemulsion drug delivery system of acyclovir for improvement of oral bioavailability. AAPS PharmSciTech, 2006, 7(3), 77.
[] [PMID: 17025257]
Pavelić, Z.; Skalko-Basnet, N.; Filipović-Grcić, J.; Martinac, A.; Jalsenjak, I. Development and in vitro evaluation of a liposomal vaginal delivery system for acyclovir. J. Control. Release, 2005, 106(1-2), 34-43.
[] [PMID: 15979189]
Cavalli, R.; Donalisio, M.; Civra, A.; Ferruti, P.; Ranucci, E.; Trotta, F.; Lembo, D. Enhanced antiviral activity of Acyclovir loaded into beta-cyclodextrin-poly(4-acryloylmorpholine) conjugate nanoparticles. J. Control. Release, 2009, 137(2), 116-122.
[] [PMID: 19361545]
Sithole, M.N.; Choonara, Y.E.; du Toit, L.C.; Kumar, P.; Marimuthu, T.; Kondiah, P.P.D.; Pillay, V. Development of a novel polymeric nanocomposite complex for drugs with low bioavailability. AAPS PharmSciTech, 2018, 19(1), 303-314.
[] [PMID: 28717975]
Tavakoli, N.; Varshosaz, J.; Dorkoosh, F.; Motaghi, S.; Tamaddon, L. Development and evaluation of a monolithic floating drug delivery system for acyclovir. Chem. Pharm. Bull. (Tokyo), 2012, 60(2), 172-177.
[] [PMID: 22293475]
Bahri-Najafi, R.; Mostafavi, A.; Tavakoli, N.; Taymouri, S.; Shahraki, M.M. Preparation and in vitro-in vivo evaluation of acyclovir floating tablets. Res. Pharm. Sci., 2017, 12(2), 128-136.
[] [PMID: 28515765]
Palombo, M.; Deshmukh, M.; Myers, D.; Gao, J.; Szekely, Z.; Sinko, P.J. Pharmaceutical and toxicological properties of engineered nanomaterials for drug delivery. Annu. Rev. Pharmacol. Toxicol., 2014, 54, 581-598.
[] [PMID: 24160695]
De Koker, S.; Hoogenboom, R.; De Geest, B.G. Polymeric multilayer capsules for drug delivery. Chem. Soc. Rev., 2012, 41(7), 2867-2884.
[] [PMID: 22282265]
Gandhi, A.; Jana, S.; Sen, K.K. In-vitro release of acyclovir loaded Eudragit RLPO(®) nanoparticles for sustained drug delivery. Int. J. Biol. Macromol., 2014, 67, 478-482.
[] [PMID: 24755259]
Davies, N.M. Biopharmaceutical considerations in topical ocular drug delivery. Clin. Exp. Pharmacol. Physiol., 2000, 27(7), 558-562.
[] [PMID: 10874518]
Rajawat, G.S.; Shinde, U.A.; Nair, H.A. Chitosan-N-acetyl cysteine microspheres for ocular delivery of acyclovir: Synthesis and in vitro/in vivo evaluation. J. Drug Deliv. Sci. Technol., 2016, 35, 333-342.
Desai, S.; Blanchard, J. An encyclopedia of pharmaceutical technology; Marcel Dekker: New York, USA, 1995.
Bourlais, C.L.; Acar, L.; Zia, H.; Sado, P.A.; Needham, T.; Leverge, R. Ophthalmic drug delivery systems--recent advances. Prog. Retin. Eye Res., 1998, 17(1), 33-58.
[] [PMID: 9537794]
Noomwong, P.; Ratanasak, W.; Polnok, A.; Sarisuta, N. Development of acyclovir-loaded bovine serum albumin nanoparticles for ocular drug delivery. Int. J. Drug Deliv., 2011, 3(4), 669.
Sharma, G.; Thakur, K.; Setia, A.; Amarji, B.; Singh, M.P.; Raza, K.; Katare, O.P. Fabrication of acyclovir-loaded flexible membrane vesicles (FMVs): evidence of preclinical efficacy of antiviral activity in murine model of cutaneous HSV-1 infection. Drug Deliv. Transl. Res., 2017, 7(5), 683-694.
[] [PMID: 28801835]
Aniagyei, S.E.; Sims, L.B.; Malik, D.A.; Tyo, K.M.; Curry, K.C.; Kim, W.; Hodge, D.A.; Duan, J.; Steinbach-Rankins, J.M. Evaluation of poly(lactic-co-glycolic acid) and poly(dl-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection. Mater. Sci. Eng. C, 2017, 72, 238-251.
[] [PMID: 28024582]
Gavini, E.; Chetoni, P.; Cossu, M.; Alvarez, M.G.; Saettone, M.F.; Giunchedi, P. PLGA microspheres for the ocular delivery of a peptide drug, vancomycin using emulsification/spray-drying as the preparation method: in vitro/in vivo studies. Eur. J. Pharm. Biopharm., 2004, 57(2), 207-212.
[] [PMID: 15018976]
Baskakova, A.; Awwad, S.; Jiménez, J.Q.; Gill, H.; Novikov, O.; Khaw, P.T.; Brocchini, S.; Zhilyakova, E.; Williams, G.R. Electrospun formulations of acyclovir, ciprofloxacin and cyanocobalamin for ocular drug delivery. Int. J. Pharm., 2016, 502(1-2), 208-218.
[] [PMID: 26899973]
Al-Dhubiab, B.E.; Nair, A.B.; Kumria, R.; Attimarad, M.; Harsha, S. Formulation and evaluation of nano based drug delivery system for the buccal delivery of acyclovir. Colloids Surf. B Biointerfaces, 2015, 136, 878-884.
[] [PMID: 26547315]
Xu, X.; Al-Ghabeish, M.; Krishnaiah, Y.S.; Rahman, Z.; Khan, M.A. Kinetics of drug release from ointments: Role of transient-boundary layer. Int. J. Pharm., 2015, 494(1), 31-39.
[] [PMID: 26241753]
Al-Subaie, M.M.; Hosny, K.M.; El-Say, K.M.; Ahmed, T.A.; Aljaeid, B.M. Utilization of nanotechnology to enhance percutaneous absorption of acyclovir in the treatment of herpes simplex viral infections. Int. J. Nanomedicine, 2015, 10, 3973-3985.
[] [PMID: 26109856]
El-Feky, G.S.; El-Rafie, M.; El-Sheikh, M.; El-Naggar, M.E.; Hebeish, A. Utilization of crosslinked starch nanoparticles as a carrier for indomethacin and acyclovir drugs. J. Nanomed. Nanotechnol., 2015, 6(1), 1-8.
Ijaz, M.; Griessinger, J.A.; Mahmood, A.; Laffleur, F.; Bernkop-Schnürch, A. Thiolated cyclodextrin: development of a mucoadhesive vaginal delivery system for acyclovir. J. Pharm. Sci., 2016, 105(5), 1714-1720.
[] [PMID: 27112405]

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