Acyclovir Research Articles

Acyclovir-Induced Nephrotoxicity: The Protective Benefit of Curcumin

Objective: Nephrotoxicity may decrease the clinical use of acyclovir (ACV). Curcumin (CUM) is used traditionally as treatments for some diseases. This study examined the protective effect of CUM against ACV-induced nephrotoxicity in rats. Materials and Methods: Forty-five male Wistar rats (240–250g) randomized into nine groups (n=5) were used. Group 1(Placebo control) received water (0.2mL/day) intraperitoneally (i.p) whereas group 2 (Solvent control) received corn oil (0.2mL/day) per oral (p.o) for 7 days. Groups 3-5 received CUM (25, 50 and 100 mg/kg/day p.o) for 7 days. Group 6 received ACV (150 mg/kg/day i.p) for 7 days. Groups 7-9 were pre-treated with CUM (25, 50 and 100 mg/kg/day p.o) before the treatment with ACV (150 mg/kg/day i.p) for 7 days. On day 8, the rats were anesthetized; blood samples were collected and evaluated for serum biochemical indices. The k idneys were weighed and assessed for histology and oxidative stress indices. Results: ACV produced no significant (p>0.05) effects on the body and kidney weights of rats when compared to control. ACV caused significant (p

Acyclovir-Loaded Nanoemulsions: Preparation, Characterization and Irritancy Studies for Ophthalmic Delivery

ABSTRACT Objective: The main goal of the present work was to develop and evaluate nanoemulsions (NEs) containing acyclovir (ACV) for ophthalmic drug delivery. Method: Firstly, component screening was performed by determining ACV solubility in various oils, surfactants, and co-surfactants. Different NE formulations were developed based on pseudo-ternary phase diagrams, and physicochemical assets were evaluated. Selected formulations were subjected to the drug release efficacy, stability studies, and ex-vivo trans-corneal permeation test. The safety of NEs was investigated by the modified Draize test and hen’s egg test-chorioallantoic membrane (HET-CAM). Results: Based on the solubility studies, Tween 20, Triacetin, and Tramsectol®P were chosen to prepare NE formulations. Developed NEs showed desirable physiochemical properties, including a droplet size of less than 15 nm. Selected formulations (F1 and F2) exhibited a sustained drug release pattern compared to the control group (P < .001). ACV penetration from F1 and F2 to the excised bovine cornea was 2.85 and 2.9-fold more than the control, respectively. Furthermore, HET-CAM and modified Draize test confirmed that F1 and F2 were safe for ocular administration. Conclusion: Present investigation revealed that ACV-loaded NEs could be effective, and safe platform for ophthalmic delivery of ACV.

Transdermal Film Loaded with Garlic Oil-Acyclovir Nanoemulsion to Overcome Barriers for Its Use in Alleviating Cold Sore Conditions.

The exponentially mounting cases of herpes simplex virus infection or cold sores have become a serious global concern. Acyclovir (ACV) and garlic oil (GO)-loaded lipid nanocarrier could be a promising therapeutic approach in alleviating cold sores, as well as limiting the biopharmaceutical constraints associated with ACV absorption and therapeutic efficacy. Therefore, the objective of the current research study was to formulate an ACV-GO self-nanoemulsifying drug delivery system (ACV-GO-SNEDDS) as transdermal films. The prepared SNEDDS was optimized using an experimental mixture design. The optimized ACV-GO SNEDDS was loaded in transdermal film and was evaluated for ex vivo skin permeation and in vivo pharmacokinetic prospects. An optimized ACV-GO SNEDDs formulation constituted of 10.4% (w/w) of GO, 64.8% (w/w) of surfactant mixture (Tween 20®-Span 20®); 24.8%(w/w) of co-surfactant (Propylene glycol®), and 200mg of ACV, respectively, were prepared and characterized for particle size (Y). The observed globule size of the optimized ACV-GO SNEDDS is 170 ± 13.45 nm. The results of stability studies indicated that the stability index of optimized ACV-GO-SNEDDS was more than 92 ± 3%. This optimized ACV-GO SNEDDS was loaded in hydroxypropyl cellulose transdermal film. The outcome of the ex vivo skin permeation study demonstrated a 2.3-fold augmented permeation of ACV from the optimized ACV-GO SNEDDS HPC transdermal film in comparison to the raw ACV transdermal film. There was a 3-fold increase in the relative bioavailability of the optimized ACV-GO SNEDDS transdermal film compared to the raw ACV-HPC film. The study findings confirmed that the ACV-GO SNEDDS transdermal film exhibited excellent potential to enhance the bioavailability of ACV.

An Updated Overview of Herpes Simplex Virus-1 Infection: Insights from Origin to Mitigation Measures

Purpose: High prevalence of recurrent HSV-1 (Herpes Simplex Virus 1) and its facile mode of transmission requires an elaborated understanding of the virus for mollification. To mitigate its pervasive nature that greatly affects both men and women, a thorough understanding of the viral genome and epidemiology are prerequisites. The review focuses on the existing facts of HSV-1 and acknowledges the prospect of ongoing epidemiological studies. Findings: Recent data indicates a surge of HSV-1 infection in the age ranged 30-50 years along with the emergence of neonatal cases. The newfound receptors indicate the effect and degree of susceptibility of the host and support the statistical data of HSV-1 seropositivity. Recent studies also show that the evolving virus has gained resistance against widely used antiviral drugs such as Acyclovir (ACV). Therefore, trials of several vaccines (eg. GEN-003and HerpV) are garnering attention as a possible prevention method. Summary: As most natural viruses are radically evolving, ensuing rather fatal consequences than previous wild types, every virus requires to be tackled with equal importance. Developing vaccines and potent drugs to eradicate viruses from infected subjects’ systems can be the only way to prevent future viral epidemics or pandemics. Therefore, early detection of the virus with accurate assay following immediate treatment can only prevent the cases from future catastrophe.

CHEMICAL MODIFICATION AND CHARACTERIZATION OF CHITOSAN FOR PHARMACEUTICAL APPLICATIONS

Nine crosslinked chitosan derivatives (CLCS) were prepared using three different types of crosslinkers: glutaraldehyde, glyoxal and terephthaldehyde. The prepared CLCS were used to control the acyclovir (ACV) release in order to improve its oral bioavailability. The CLCS were prepared by Schiff based reaction and characterized by means of infrared spectroscopy (FTIR), x-ray diffraction measurements, thermogravimetric inspection, differential scanning calorimetry, and scanning electron microscopy (SEM). Establishment of an imine (C=N) bond was evidenced in FTIR. Compared to raw chitosan, the crosslinked chitosan derivatives showed more amorphous structure and exhibited more water holding capacity that increased with raising the crosslinking percent. In SEM, the CLCS demonstrated areas with rough surfaces and grooves that did not present in the smooth chitosan surface. The difference in swelling degree with varying crosslinker amount was also examined. The crosslinked chitosan displayed less swelling and the degree of swelling decreased with increasing the density of crosslinking agent. The CLCS investigated in controlling the release of acyclovir by being incorporated with ACV in granules formulations. In vitro drug release results exhibited sustained release of ACV affected by the type and percent of crosslinker.

Novel nanoparticle-size metal complexes derived from acyclovir. Spectroscopic characterization, thermal analysis, antitumor screening, and DNA cleavage, as well as 3D modeling, docking, and electrical conductivity studies

Novel nano-sized Cr(III), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes derived from acyclovir (ACV) were synthesized in different media. The synthesized metal complexes were characterized by different analytical and spectroscopic techniques. The ACV behaves as a bidentate (NO) chelating ligand. All complexes showed octahedral geometry, except Zn(II) complex which exhibited a tetrahedral geometry. The TGA results confirmed thermally stability of these complexes. The XRD patterns and TEM images indicated that the particles of the investigated complexes were situated in nano-scale range. The data obtained from the computational estimation agree well with the experimental results. The results of antimicrobial screening revealing enhancement in activity upon complex formation. All investigated compounds exhibited an inhibition of HEPG-2 cell growth. Additionally, the antitumor activity of the nano-scale complexes were enhanced after heating of them at 200 °C for 1 hour. The DNA cleavage study showed that the Cu(II) complex XXVII may be able to induce cellular death in cancer cells through apoptosis/necrosis pathways. The docking analysis revealed that the nano-sized Cu(II) complex V has stronger binding affinity to DNA than the free ligand ACV. Furthermore, the electrical conductivity measurements indicated that the ACV and its investigated nano-sized complexes behave as semiconductors, and the hopping model is applicable to describe the mechanism of conduction process.

In vitro anticancer activity of thiazole based β-amino carbonyl derivatives against HCT116 and H1299 colon cancer cell lines; study of pharmacokinetics, physicochemical, medicinal properties and molecular docking analysis

The present study describes the synthesis and anticancer evaluation of certain substituted rac-(2S)-2-[(R)-[(4-substitutedphenyl){[4-(4-substitutedphenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone derivatives. The in vitro anti-cancer assay indicating substituted β-amino carbonyl derivatives 4g and 4r are particularly active in both tests (HCT116 and H1299). The 4f, 4o , and 4t are the least functioning; 4m and 4n are marginally active; 4b and 4c are more cytotoxic when the growth inhibition percent is compared with standard drugs Camptothecin (CPT.), Acyclovir (ACV), Cisplatin (CDDP.), Vinblastine (VBL) and Trichothecene (TCT.). Among them, 2-((4- p -tosylthiazol-2-ylamino)(4-hydroxyphenyl)methyl) cyclohexanone 4u exhibits selective cytotoxicities for IC 50 µg/mL against HCT116 and H1299, respectively. Simulation of virtually designed 21 compounds has been studied for active binding sites of Crystal Structure of the Cancer Genomic DNA Mutator APOBEC3B (PDB ID- 5CQD) enzyme using molecular modelling of protein-ligand interactions. The in-depth sequencing studies reveal that the involvement of APOBEC3B in cancer mutagenesis. For comparison, the binding behaviour of known standard drugs has also studied. The new SwissADME web utensil that gives free access to a pool of quick yet reliable analytical models is presented for physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry. Among them, in-house capable technique, for example, BOILED-Egg, iLOGP, and Bioavailability Radar, are readily available on the web.

Cucumis melo pectin as potential candidate to control herpes simplex virus infection.

The herpes simplex virus, also known as HSV, is an important human pathogen. Acyclovir (ACV) is the first-line antiviral for the treatment of HSV infections; nevertheless HSV resistance to ACV has been increasingly reported and, therefore, search for alternative drugs have been encouraged. Herein, the effect of Cucumis melo sulfated pectin (SPCm) was evaluated in the HSV-1 infection. Pectin cytotoxicity and its antiherpetic action were determined by assays of MTT and plaque reduction, respectively. The SPCm concentration that reduced the cell viability by 50% (CC50) was 1440μg/mL, while the concentration that reduced PFU in 50% (IC50) was 6μg/mL against ACV-sensitive (KOS) strain and 12μg/mL for ACV-resistant (AR-29) strain. The pectin showed high selectivity index (SI) for both viral strains. Therefore, we suggest that SPCm has been effective for HSV-1, strenghten by viral protein and DNA syntheses inhibition. In conclusion, we have found that SPCm is a promising alternative compound to control HSV infection.

Development of Lipid-Drug Conjugate Nanoparticles for Hydrophilic and Lipophilic Drug: A Comparative Ex vivo Gut and Caco-2 Cell Permeability Study

Background: The lipid-drug conjugate nanoparticles (LDC NPs), amongst other lipidbased nanoparticles, are the most accepted ones for the oral delivery of both hydrophilic and hydrophobic drugs with poor bioavailability. Besides, the LDC NPs show altered physicochemical properties of the drug and have the potential applications in targeting the drug to a specific organ. Objective: To synthesize hydrophilic Valacyclovir (VACV)-stearic acid (SA) and lipophilic Acyclovir (ACV)-stearic acid conjugates (VACV-SAC and ACV-SAC), and develop their nanoparticles (VACV-LDC-NPs and ACV-LDC-NPs) for improved intestinal permeability. Methods: Both VACV-SAC and ACV-SAC were synthesized and confirmed using FTIR, NMR, and DSC techniques and characterized for assay. The lipid drug conjugate nanoparticles (LDC NPs) were prepared using cold high-pressure homogenization technique and characterized for drug content, mean particle size, zeta potential, ex vivo gut permeability using rat gut sac model, and Caco-2 cell permeability. Results: The FTIR, NMR, and DSC results confirmed the successful synthesis of LDCs. The assay of VACV-SAC and ACV-SAC was found to be 51.48±5.6% and 41.2±6.2%, respectively. The VACV-LDC-NPs and ACV-LDC-NPs showed %EE of 99.10±6.71% and 86.84±5.32%, the mean particle size of 338.7±8nm and 251.3±7nm and zeta potential of -10.8±2.31mV and -11.2±3.52mV respectively. About 91±5.2% of VACV and 84±6.5% of ACV were found permeated across the rat intestine after 480 minutes from their respective NPs. Furthermore, VACV-LDC-NPs and ACVLDC- NPs displayed a significantly higher permeability coefficient (61.5×10-6 and 59.8×10-6 cm/s, respectively) than their plain solutions. Conclusion: The obtained remarkable permeability characteristics indicate developed LDC NPs are the potential, promising and translational approaches for effective oral delivery of poorly bioavailable hydrophilic and lipophilic drugs. Furthermore, this approach may result in moderately to significantly enhanced oral bioavailability of hydrophilic drugs as the conjugation results in amphiphilic molecules, which are further absorbed through different mechanisms across the intestinal mucosa (mainly through passive diffusion mechanism).

In vitro, ex vivo, and in vivo studies of binary ethosomes for transdermal delivery of acyclovir: A comparative assessment

The study investigated a comparative assessment of binary ethosomes (ETHOs) and elastic liposomes (ELPs) for transdermal delivery of acyclovir sodium (ACV-Na). Optimized binary ETHO (ETHO2) and ELPs (ELP3) were evaluated for vesicle size, entrapment efficiency, elasticity, extruded volume, in vitro drug release, morphology, ex vivo skin permeation, and drug deposition (albino rat skin). In vivo studies were performed to evaluate transepidermal water loss (TEWL) and skin irritation. The components of ELP3 and ETHO2 (ethanol, propylene glycol, Tween 80, lipids) had a significant impact on in vitro and in vivo parameters. ETHO2 showed convincing findings as compared to ELP3. The permeation steady-state flux (Jss) and enhancement ratio (ER) were significantly (p˂0.05) enhanced in ETHO2 (Jss = 87.6 ± 4.8 μg/cm2/h and ER = 7.3) as compared to drug solution (DS) (Jss = 12 ± 2.6 μg/cm2/h) and marketed cream (Jss = 52 ± 7.0 μg/cm2/h and ER = 4.3). The findings of TEWL and scanning electron microscopy confirmed better permeation of ETHO2. Hemolysis and Draize studies confirmed the hemocompatibility and non-irritant behavior of formulations, respectively. Conclusively, ETHO2 can be a suitable alternative to classical vesicular systems for transdermal application against infections caused by the herpes simplex virus.

Antimicrobial prophylaxis in patients with immune thrombocytopenia treated with rituximab: a retrospective multicenter analysis.

The primary aim of this study was to describe the use of primary anti-infective prophylaxis (AP) in common clinical practice in patients affected by immune thrombocytopenia (ITP) and treated with RTX. Population studied consisted of patients affected by ITP (age ≥ 18years) who had received at least one dose of RTX from January 2008 to June 2018. Five Italian haematology centres participated in the current study. Data were retrospectively collected: demographic data (age, gender), concomitant comorbidities and previous therapies for ITP, characteristics of AP, the occurrence of infections and their management. The ITP cohort consisted of 67 patients sub-grouped into two categories according to the administration of AP: (1) treated with AP (N= 34; 51%) and (2) not treated with AP (N=33, 49%). AP consisted of combined trimethoprim/sulfamethoxazole (TMP/SMX) and acyclovir (AC) in half of patients. TPM/SMX as a single agent was adopted in 32% patients and one patient received only AC. Overall, infections were experienced in 15% of patients during follow-up with a similar proportion in the 2 groups (treated and not treated) of patients (14.7% vs 15%). Clinical course of infections was however, less severe in patients treated with AP, where all infections were grade 2 and did not require hospitalization. In neither group of patients was reported Pneumocystis pneumonia. In conclusion, despite the absence of clear evidence, our analysis shows that AP in patients with ITP receiving RTX is frequently adopted, even if in the absence of well-defined criteria. Prophylaxis administration is quite consistent within the same haematological Center; thus, it seems related to clinicians' experience.

Pluronic F127-tailored lecithin organogel of acyclovir: preclinical evidence of antiviral activity using BALB/c murine model of cutaneous HSV-1 infection.

Herpes is a well-known contagious infection equally affecting both sexes. Among many antiviral drugs employed for its treatment, acyclovir (ACY) is the drug of choice. The currently available therapies of ACY suffer from limitations like poor oral bioavailability (10-15%) and high-dose requirement. The present scientific study aims to explore pluronic lecithin organogel (PLO) as a novel drug delivery platform for ACY to bring an improvement in its delivery through topical route. The properties of organogel like biocompatibility and amphiphilic nature which facilitates dissolution of various drugs of different solubility characteristics along with enhancing the permeation potential of active molecules make it a favorable drug delivery platform for the management of topical diseases. The developed PLO formulations were characterized for micromeritic characteristics, viz., zeta potential, percentage drug content, organogel morphology, skin permeation, retention, and stability studies. The selected topical formulation was further compared with the marketed one for its therapeutic efficacy by inducing cutaneous Herpes simplex virus type 1 infection followed by confirmation of viral load by immunofluorescence and PCR analyses. The developed formulation showed significant improvement over the marketed product as reflected in lesion scoring index and PCR analysis. Further, it proved better to the marketed formulation in t.i.d. treatment regimen in comparison to control. The improvement in overall performance leading to enhanced bioavailability and safety is attributed to the synergism between excipient properties and formulation characteristics. The drug ACY in this micro environment not only finds an improved delivery vehicle but it also offers enhanced drug-target interactions.

Acyclovir As a Potential Add-On Treatment for COVID-19; A Narrative Review

Introduction: There are successful reports of the concomitant management of herpes infection and coronavirus disease 2019 (COVID-19), using both acyclovir (ACV) and COVID-19 treatment regimens. Furthermore, ACV has been proposed to effectively treat COVID-19, through various mechanisms, such as inhibition of viral proteases, multiple viral gene expressions, and RNA-dependent RNA polymerase (RdRP). Therefore, this study aimed to review the reported cases of patients with concomitant herpes infection and COVID-19, receiving concurrent antiviral drugs for herpetic lesions. Methods: A search was done to find the relevant articles, published between December 2019 and December 2020, with no language limitations, in the PubMed database, using the Medical Subject Headings (MeSH) terms related to herpes simplex virus or herpes zoster (namely, shingles) combined with COVID-19. Accordingly, the reports of the concomitant herpes infection and COVID-19, receiving concurrent antiviral drugs for herpetic lesions were included. Results: Out of 90 articles, 11 records reporting the cases of herpes infection and concurrent laboratory-confirmed COVID-19, receiving antiherpetic therapies, were reviewed. There were 28 patients (age range of 7-82 years) with laboratory-confirmed COVID-19, concomitant with reactivation of herpes infection, receiving antiviral drugs alongside candidate COVID-19 treatment regimens, but no mortality. The mean (standard deviation [SD] range) age of these 28 patients during treatment was 56.4 (18.6 [7-82]) years, and the majority were male (n=18, 64.3%). A total number of 20 patients had also received ACV and eight cases had been administered with other two antiviral compounds, including seven cases with valacyclovir, and one case with famciclovir, with no mortality. Conclusion: The potential use of ACV, as an add-on therapy, along with candidate COVID-19 treatment regimens was proposed in this study. However, further clinical trials are recommended to test this hypothetical adjuvant therapy.

Pentostatin antagonizes the antiviral activity of MBX-2168 by inhibiting the biosynthesis of the active compound

MBX-2168 has a mechanism of action similar to that of acyclovir (ACV) and ganciclovir (GCV), but two unique steps differentiate this drug from ACV/GCV. First, MBX-2168 is, at least partially, phosphorylated by the endogenous cellular kinase TAOK3 to a monophosphate. The second involves the removal of a moiety at the 6-position of MBX-2168-MP by adenosine deaminase like protein-1 (ADAL-1). It has been previously demonstrated that co-incubation with pentostatin (dCF), an ADAL-1 inhibitor, antagonizes the anti-viral activity of MBX-2168. We therefore hypothesize that inhibiting ADAL-1 results in a reduction of active compound produced in virus-infected cells. To test this, we examined the effect dCF has on the conversion of MBX-2168 to a triphosphate in HSV-1 and HCMV-infected cells. Our results demonstrate incubation of MBX-2168 alone or with dCF in HCMV-infected cells resulted in 53.1 ± 0.7 and 39.4 ± 1.5 pmol triphosphate/106 cells at 120 h, respectively. Incubation of MBX-2168 alone or with dCF in Vero cells resulted in 12.8 ± 0.1 and 6.7 ± 0.7 pmol triphosphate/106 cells at 24 h, respectively. HSV-1-infected Vero cells demonstrated no statistical difference in triphosphate accumulation at 24 h (13.1 ± 0.3 pmol triphosphate/106 cells). As expected, incubation with dCF resulted in the accumulation of MBX-2168-MP in both HFF (9.8 ± 0.9 pmol MBX-2168-MP/106 cells at 120 h) and Vero cells (4.7 ± 0.3 pmol MBX-2168-MP/106 cells at 24 h) while no detectable levels of monophosphate were observed in cultures not incubated with dCF. We conclude that dCF antagonizes the anti-viral effect of MBX-2168 by inhibiting the production of triphosphate, the active compound.

Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice.

Herpes simplex virus type 1 (HSV-1) causes a lifelong latent infection with an estimated global prevalence of 66%. Primary and recurrent HSV infections are characterized by a tingling sensation, followed by an eruption of vesicles, which can cause painful erosions. Commonly used antiviral drugs against HSV infection are nucleoside analogues including acyclovir (ACV), famciclovir, and valacyclovir. Although these nucleoside analogues reduce morbidity and mortality in immunocompetent individuals, ACV-resistant HSV strains (ACVR-HSV) have been isolated from immunocompromised patients. Thus, ACVR-HSV infection poses a critical emerging public health concern. Recently, we reported that ginkgolic acid (GA) inhibits HSV-1 by disrupting viral structure, blocking fusion, and inhibiting viral protein synthesis. Additionally, we showed GA affords a broad spectrum of fusion inhibition of all three classes of fusion proteins, including those of HIV, Ebola, influenza A and Epstein Barr viruses. Here we report GA’s antiviral activity against HSV-1 skin infection in BALB/cJ mice. GA-treated mice demonstrated a significantly reduced mortality rate and decreased infection scores compared to controls treated with dimethylsulfoxide (DMSO)-vehicle. Furthermore, GA efficiently inhibited ACVR-HSV-1 strain 17+ in vitro and in vivo. Since GA’s mechanism of action includes virucidal activity and fusion inhibition, it is expected to work alone or synergistically with other anti-viral drugs, and we anticipate it to be effective against additional cutaneous and potentially systemic viral infections.

Influência dos excipientes nas propriedades de fluxo e dissolução de cápsulas manipuladas de aciclovir.

Acyclovir (ACV) is used to treat infectious diseases caused by the herpes virus. Its high cohesiveness makes encapsulation difficult and compromises the final quality of the compounded product. The aim of this work was to select excipients capable of improving the flow properties of ACV in relation to the preparation of compounded capsules with 400 mg of the active pharmaceutical ingredient (API) and to guarantee the recommended dissolution rate. Eight blends of excipients (A – H) distinctly composed of colloidal silicon dioxide (DSC), sodium starch glycolate, purified talc, hydroxypropyl cellulose and microcrystalline cellulose (MCC) were evaluated for flowability, where four of them (A, B, C and E) were selected to compose the capsule formulations because they exhibit the lowest values referring to the Hausner Factor and the Carr index. The ACV assay showed purity content of 99.3%. Although all formulations have approved the weight determination criteria, only capsules containing ACV and E blend (DSC:MCC) achieved the specified dissolution rate. This indicates that the association of such excipients provided appropriate porosity to the ACV particles through the reduction of interparticular cohesion, a fact that favored the penetration of water in the packaged powder blend. Finally, it is suggested that the production of compounded capsules containing ACV 400 mg be carried out employing capsule shells of size No00 with approximately 190 mg of DSC and MCC (2.5:97.5) in order to aid the flow of the API, provide adequate weight uniformity and achieve the desired dissolution rate to promote an effective antiviral therapy

Neem Fruit Mucilage Impact on Acyclovir Release at Different Intervals : A Central Composite Design Screening

The drive of this exploration is to look into the supportive mucoadhesive assets of neem (Azadirachta indica) fruit mucilage by incorporating it into mucoadhesive microspheres by taking Acyclovir (ACR) as a model drug. Nine interpretations of mucoadhesive microspheres were made with Methocel 934P and varying proportions of Neem fruit mucilage (NFM). A central composite design with design expert software to check the impact of independent variables (neem mucilage and methocel 934 P levels) on ACR

β-cyclodextrin chitosan-based hydrogels with tunable pH-responsive properties for controlled release of acyclovir: design, characterization, safety, and pharmacokinetic evaluation

In this work, series of pH-responsive hydrogels (FMA1–FMA9) were synthesized, characterized, and evaluated as potential carrier for oral delivery of an antiviral drug, acyclovir (ACV). Different proportions of β-cyclodextrin (β-CD), chitosan (CS), methacrylic acid (MAA) and N′ N′-methylenebis-acrylamide (MBA) were used to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy confirmed fabrication of new polymeric network, with successful incorporation of ACV. Scanning electron microscopy (SEM) indicated presence of slightly porous structure. Thermal analysis indicated enhanced thermal stability of polymeric network. Swelling studies were carried out at 37 °C in simulated gastric and intestinal fluids. The drug release data was found best fit to zero-order kinetics. The preliminary investigation of developed hydrogels showed a pH-dependent swelling behavior and drug release pattern. Acute oral toxicity study indicated no significant changes in behavioral, clinical, or histopathological parameters of Wistar rats. Pharmacokinetic study indicated that developed hydrogels caused a significant increase in oral bioavailability of ACV in rabbit plasma as compared to oral suspension when both were administered at a single oral dose of 20 mg kg−1 bodyweight. Hence, developed hydrogel formulation could be used as potential candidate for controlled drug delivery of an antiviral drug acyclovir.

Lupeol impairs herpes simplex virus type 1 replication by inhibiting the promoter activity of the viral immediate early gene α0.

Herpes simplex virus type 1 (HSV-1) is an important human pathogenic virus. It is urgent to develop novel antiviral targets because of the limited treatment options and the emergence of drug resistant strains. In this study, we tested the antiviral activity of lupeol, a triterpenoid compound, against HSV-1 and acyclovir (ACV) resistant strains. Lupeol significantly inhibited HSV-1 (F strain) and ACV-resistant strains including HSV-1/106, HSV-1/153, and HSV-1/Blue. Lupeol activity of the HSV-1α0 and α4 promoters, therefore down regulating the expression of the α0, α4, and α27 genes. Collectively, lupeol showed strong antiviral activity against HSV-1 and ACV-resistant strains, and could be a promising therapeutic candidate for HSV-1 pathogenesis. Keywords: herpes simplex virus 1; lupeol; ACV-resistant strains; promoter.

Effects of epigallocatechin-3-gallate and acyclovir on herpes simplex virus type 1 infection in oral epithelial cells

Herpes simplex virus type 1 (HSV-1) is the pathogenic agent of human diseases, including gingivostomatitis and herpes labialis. The anti-viral activities of the tea polyphenol, epigallocatechin-3-gallate (EGCG), have been demonstrated. This study examined the combined effects of EGCG and the antiviral drug, acyclovir (ACV), on infection of HSV-1 in oral epithelial cells. Cell viability was examined using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide. Viral yields were determined using the plaque assay. Viral proteins were detected using Western blotting analysis or confocal laser scanning microscopy. Viral DNA was detected using the real-time polymerase chain reaction. Cytotoxic effects of HSV-1 on the viability of oral epithelial cells were evidently reduced in the presence of EGCG (25μg/ml) or/and ACV (50μg/ml). Viral yields were also significantly reduced by treatment of cells with EGCG or/and ACV. Expression of viral immediate early protein, infected cell protein 0 (ICP0), was greatly inhibited when cells were treated with EGCG. Combined effects of EGCG and ACV were more evident for the expression of viral thymidine kinase, ICP5 and glycoprotein D. EGCG, but not ACV, significantly reduced the levels of viral particles and viral DNA during viral entry phase. However, at 20h post infection, the intracellular viral DNA was evidently reduced in HSV-1 infected cells treated with EGCG and ACV. Moreover, the stimulatory effects of HSV-1 on phosphorylation of c-Jun N-terminal kinase could be reduced by ACV. The results demonstrated the additive effects of EGCG and ACV on HSV-1 infection in oral epithelial cells.