Treatment Of Herpesvirus Infections Research Articles

Formulation and Evaluation of Famciclovir Microsphere Loaded Capsule for the Treatment of Herpes Virus Infection

Formulation and Evaluation of Famciclovir Microsphere Loaded Capsule for the Treatment of Herpes Virus Infection

Enhanced Topical Co-delivery of Acyclovir and Lidocaine Gel Formulation Across Dermatomed Human Skin.

Acyclovir a widely used drug in the treatment of herpes simplex virus (HSV) infections and lidocaine a local anesthetic were combined in a topical gel formulation. The topical gel with Transcutol P (TP) or N-methyl 2-pyrrolidone (NMP) was prepared and tested for in vitro skin permeation across the intact and microneedle-treated human cadaver skin. The topical gels containing 5% each of acyclovir and lidocaine showed optimal pH, spreadability, and 100% drug release. The transdermal flux and skin retention of the gels were significantly higher compared to Generic 5% acyclovir ointment (Zovirax) (p < 0.001), and 5% lidocaine gel (numb gel) (p < 0.05). As expected, topical gels showed a very high increase in the skin permeation across microporated skin versus intact skin. In viral infections, skin is inflamed, and barrier integrity may be disrupted. The results of the present study are significant because the co-delivery formulation showed a very high increase in the skin permeation across intact and microporated skin (versus respective commercial formulations). The results of this study demonstrate enhanced co-delivery of acyclovir and lidocaine in a topical formulation across skin (intact or barrier compromised) for the treatment of herpes virus infections.

In vitro antiviral activities of fruit extract from Lycium barbarum and methylxanthines extracted from Pu-erh and Bancha tea leaves.

Based on traditional medicine, many countries use various plant products (fruits, leaves and other plant parts) as food supplements or in the form of tea. The use of these plant sources has been established through the years of use and the proven benefits of their ingredients to improve human health.

Acyclovir Induced Neurotoxicity in Patients With Chronic Kidney Disease

Acyclovir is highly useful for treatment of herpes virus infection. It is excreted primarily by kidneys. Therefore it gets accumulated in patients with renal dysfunction. There are reports to suggest that acyclovir usage could lead to neurotoxicity characterized by disorientation, decreased level of consciousness, dysarthria, tremors, seizures, hallucinations and coma. Acyclovir induced neurotoxicity has been found with patients on dialysis or not on dialysis. We present here five cases of CKD who developed neurotoxicity after use of acyclovir for herpes zoster. They had disorientation, decreased level of consciousness, dysarthria, tremors, seizures and hallucinations 2-4 days after administration of acyclovir. Acyclovir induced neurotoxicity was suspected because we could not find any other cause for neurological symptoms in these patients. Acyclovir was discontinued in all cases and haemodialysis sessions were given. One patient was managed by increasing number of exchanges of peritoneal dialysis. All patients recovered in 3-5 days after discontinuation of drug. Main factors for acyclovir induced neurotoxicity are advance age , renal failure, inappropriate dose of acyclovir in relation to creatinine clearance. Acyclovir induced neurotoxicity should be suspected in patients with renal dysfunction those present with neurological symptoms 2=4 days after taking of drug. These patients should be treated with discontinuation of acyclovir and judicious use of haemodialysis. Physicians should adjust the dose of acyclovir according to creatinine clearance to minimize toxicity.

Antiviral activity of the organic germanium complex with aciclovir against herpes simplex virus (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1/2) in the in vitro and in vivo systems

A significant increase in the incidence of various forms of herpesvirus infection (HVI) determines the need to search for new approaches to the modification of one of the basic antiviral drugs aciclovir (ACV) and its dosage forms to improve their biopharmaceutical characteristics and increase the effectiveness of therapy. In this aspect, an innovative organic germanium complex with aciclovir (OGCA) is promising.The aim of the study was to assess the antiviral activity of OGCA against the herpes simplex virus (HSV) (human herpes virus, HHV) on the HVI models both in vitro and in vivo. We studied the activity of OGCA in a therapeutic regimen against HSV-1 (HHV-1) (Kl strain), HSV-2 (HHV-2) (VN strain) using virological and statistical research methods in the in vitro model of HVI on Vero cell culture and the model of genital herpes (GH) caused by HHV-2 (VN strain) in male guinea pigs (Canis porcellus). It was found OGCA inhibits the replication of HHV-1 and HHV-2 in Vero cells, and has anti-HHV activity in the GH model in male guinea pigs, leading to a decrease in the severity and duration of the disease, the intensity and duration of viral shedding. The most pronounced activity was detected when preparation was applied topically 5 times a day for 5 days at the early stages of infection (3% gel). The delayed use of OGCA (48 hours after infection) also had statistically significant efficacy compared to commercial reference drugs containing aciclovir or its pro-drugs: aciclovir (5% cream), AIL (acyclovir+interferon alfa-2b+lidocaine, 3% ointment), penciclovir (1% cream). OGCA significantly reduced the number of days of the pathogen shedding, as well as its infectivity, compared to animals in the control group and ones receiving placebo. The activity of OGCA, apparently, is due to its improved biopharmaceutical characteristics compared to aciclovir, as well as the presence of a number of biological activities of its constituent components. The results of the study allow us to consider OGCA as the basis for the development of antiviral agents for the treatment of HVI.

Современные проблемы, диагностика и лечение герпесвирусных инфекций

В статье приводятся данные современной литературы об актуальности, проблемах, сложности диагностики и лечения герпесвирусных инфекций.

Герпесвирусы. Часть 2

The clinical manifestations of herpes infection depend on the pathogenic properties of the pathogen and on the state of immunity of the infected organism. Herpesviruses type 1-3 are predominantly neurotropic and cause diseases of the nervous system. The reproduction of the virus is carried out in the neurons of the nerve ganglia and epithelial cells, as they have a common ectodermal origin. Herpesviruses type 4, 5 and 8 are predominantly lymphotropic and cause diseases of the immune system. In a latent and persistent state, viruses are found in lymphocytes, monocytes, polymorphonuclear leukocytes, as they exhibit tropism for cells of mesenchymal origin. When the infection is reactivated, the virus is reproduced in cells of ectodermal origin, which leads to characteristic organ lesions. Type 6 and 7 viruses are both neurotropic and lymphotropic. They are capable to infect T-lymphocytes, B-lymphocytes, epithelial cells, endothelial cells, hepatocytes, fibroblasts, glial cells, stem cells, monocytes, macrophages, leukocytes, etc. They are able to promote the reactivation of other viruses, forming mixed forms, which leads to an aggravation of the clinical picture of the disease. Therapy of herpesvirus infections should be scientifically grounded, consistent, gradual, complex and include: specific antiviral treatment; immunotherapy; antibacterial therapy; detoxification therapy; symptomatic treatment and therapeutic measures aimed to eliminate various complications. Antiviral drugs for the treatment of herpes infection are divided into 4 groups: nucleoside analogs; drugs that cause the destruction of viruses located extracellularly; drugs that are active against intracellular viruses; drugs with a double effect. Modern therapy of herpesvirus infections is capable to suppress the reproductive activity of the reactivated virus, modulate the body's immune response, prevent and eliminate various complications of herpes infections, but is unable to affect the latent form of viruses. In the complex therapy of herpes infection, along with the specific treatment methods aimed to destroy the virus and to enhance the body's immunity, it is necessary to apply the entire range of therapeutic measures that help eliminate the accompanying symptoms and complications of diseases caused by herpesviruses

Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways.

Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, Epstein–Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases.

Клинико-лабораторное обоснование и оценка эффективности рекомбинантного интерферона α-2b в терапии генитального герпеса

According to the World Health Organization, a significant part of the population is susceptible to diseases caused by herpes viruses, among which genital herpes occupies a leading position in the incidence and severity of clinical manifestations. A promising strategy for the treatment of herpesvirus infections caused by herpes simplex virus (HSV) types 1 and 2 is the use of recombinant interferon-α preparations. Objective. To conduct a comparative analysis of the efficacy of using recombinant interferon α-2b with an active substance content of 1.000.000 IU and 3.000.000 IU in the treatment of genital herpesvirus infection. Patients and methods. A retrospective study of 100 patients with recurrent genital herpes 5.5 ± 1.25 per year at the age from 20 to 52 was carried out. The diagnosis was made based on complaints, clinical examination results and laboratory parameters. The presence of herpes virus antigen in the sample material, clinical status, clinical and biochemical parameters of peripheral blood, and the activity of antioxidant enzymes were assessed. Results. The maximum efficacy of therapy for genital herpesvirus infection was registered in patients who received complex treatment with valacyclovir and recombinant interferon α-2b with antioxidants at a dosage of 3.000.000 IU. Key words: antioxidant status, genital herpes, immunity, interferon α-2b

ОСОБЕННОСТИ ТЕЧЕНИЯ, ПРОФИЛАКТИКА И ЛЕЧЕНИЕ ГЕРПЕТИЧЕСКИХ ИНФЕКЦИЙ В ПЕРИОД БЕРЕМЕННОСТИ

The features of the course of herpetic infections in women during pregnancy and the manifestations of the results of infection of their children are highlighted. The tactics of observation and principles of examination of these women have been determined. Genital herpes is the most common sexually transmitted ulcer disease. In terms of teratogenic significance, herpes viruses rank second after rubella, and CMV is classified as an indisputable viral teratogen. Fetal lesions vary from blasto- and embryopathies, accompanied by early termination of pregnancy, to late fetopathies with damage to various organs and systems in the newborn. The article presents the clinical and pharmacological characteristics of antiviral drugs for the prevention and treatment of herpes infections at the stages of planning and the course of pregnancy in antenatal clinics and hospitals.

Acyclovir in the Treatment of Herpes Viruses - A Review.

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. 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. 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.

Fabrication of Non-Enzymatic Sensor Utilizing Carbon Nanotubes- Nafion Film for Nanoscale Determination of Antiviral Drug

Rapid emergence of viral diseases has posed a consequential threat to all human and veterinary health. Over past two decades these diseases are major cause of death among all infectious diseases worldwide. Acyclovir (ACV) which is a synthetic purine based nucleoside analogue plays a pivotal role in the therapy of viral diseases and possesses the best safety profile of all antivirals licensed so far. ACV is an emerging drug for the clinical treatment against herpes simplex virus, hepatitis B virus, varicella zoster virus and epstein-barr virus. ACV is marketed in the form of ophthalmic ointments, dermal cream, injections, capsules and oral tablets which have been extensively and effectively used for the treatment of herpes virus infections. The drug provides remarkable therapeutic benefit in the therapy of viral diseases like cold sores, keratitis, corneal blindness, encephalitis and virally infected central nervous system. Several adverse outcomes like neurotoxicity, nephrotoxicity, urticaria, phlebophlogosis, diarrhoea, cephalalgia, emesis and swoon are associated with higher intake of ACV and its abuse. Various analytical techniques other than electrochemical have several inconveniences which include lengthy and tedious sample preparation procedures, long analysis time and need of trained technicians. Chromatographic methods suffer from consumption of large volumes of high purity organic solvents and requirement of expensive sophisticated instruments. These methods also suffer from lack of selectivity and sensitivity which makes them unsuitable for routine analysis. In recent years, much attention has been focused on the preparation of a variety of nanomaterials with highly controllable size, shape, surface charge and physicochemical characteristics. The alluring properties of nanomaterial exhibit signal amplification due to which they are prodigiously used for the fabrication of a wide range of electrochemical sensors. Single walled carbon nanotubes (SWNTs) displaying quantum dots and wires at very low temperatures enhances the electrode conductivity and facilitates the electron transfer between myriad electroactive species and the underlying electrode. Nafion which is a sulfonated tetrafluorethylene copolymer possessing pronounced antifouling capacity, chemical inertness, strong adsorption ability, thermal stability and biocompatibility renders it to be extensively employed as an electrode modifier. A simple and sensitive approach is proposed for the accurate monitoring of antiviral drug ACV utilizing glassy carbon electrode (GCE) fabricated with SWNTs and nafion composite film employing square wave voltammetry for the first time. The developed sensor exhibits effective and sustained electron mediating behavior displaying higher peak currents at lower potential than those obtained at bare GCE. The developed sensor engendered ∼2.5 fold larger electroactive surface area in comparison to bare GCE which substantially accelerated the rate of electron transfer via improved electrical conductivity. At optimal experimental conditions, oxidation current showed a wide linear response for ACV in the concentration range from 10 nM to 30 µM. The proposed sensor exhibited pronounced analytical performance for the determination of ACV with limit of detection corresponding to 1.8 nM and high sensitivity of 15.4 µA µM-1. The modified sensor showcased high recognition selectivity, fair reproducibility and long term stability of signal response in the physiological environment. The developed prototype was successfully implemented to quantify ACV in several commercially available pharmaceuticals. The versatile method described herein was efficaciously applied further in detecting ACV in real human urine sample of patient undergoing pharmacological treatment with ACV. The results explicitly demonstrate the applicability of the developed sensor in quality control, pharmacokinetic studies and clinical analysis.

Sensing Platform for Antiviral Drug in Pharmaceuticals and Human Physiology Exploiting Electrocatalytic Properties of Carbon Nanomaterials

In recent years, much attention has been focused on the preparation of a variety of nanomaterials with highly controllable size, shape, surface charge and physicochemical characteristics. The alluring properties of nanomaterial exhibit signal amplification due to which they are prodigiously used for the fabrication of a wide range of electrochemical sensors. Single walled carbon nanotubes (SWNTs) displaying quantum dots and wires at very low temperatures enhances the electrode conductivity and facilitates the electron transfer between myriad electroactive species and the underlying electrode. Nafion which is a sulfonated tetrafluorethylene copolymer possessing pronounced antifouling capacity, chemical inertness, strong adsorption ability, thermal stability and biocompatibility renders it to be extensively employed as an electrode modifier. Rapid emergence of viral diseases has posed a consequential threat to all human and veterinary health. Over past two decades these diseases are major cause of death among all infectious diseases worldwide. Acyclovir (ACV) which is a synthetic purine based nucleoside analogue plays a pivotal role in the therapy of viral diseases and possesses the best safety profile of all antivirals licensed so far. ACV is an emerging drug for the clinical treatment against herpes simplex virus, hepatitis B virus, varicella zoster virus and epstein-barr virus. ACV is marketed in the form of ophthalmic ointments, dermal cream, injections, capsules and oral tablets which have been extensively and effectively used for the treatment of herpes virus infections. The drug provides remarkable therapeutic benefit in the therapy of viral diseases like cold sores, keratitis, corneal blindness, encephalitis and virally infected central nervous system. Several adverse outcomes like neurotoxicity, nephrotoxicity, urticaria, phlebophlogosis, diarrhoea, cephalalgia, emesis and swoon are associated with higher intake of ACV and its abuse. Various analytical techniques other than electrochemical have several inconveniences which include lengthy and tedious sample preparation procedures, long analysis time and need of trained technicians. Chromatographic methods suffer from consumption of large volumes of high purity organic solvents and requirement of expensive sophisticated instruments. These methods also suffer from lack of selectivity and sensitivity which makes them unsuitable for routine analysis. A simple and sensitive approach is proposed for the accurate monitoring of antiviral drug ACV utilizing glassy carbon electrode (GCE) fabricated with SWNTs and nafion composite film employing square wave voltammetry for the first time. The developed sensor exhibits effective and sustained electron mediating behavior displaying higher peak currents at lower potential than those obtained at bare GCE. The developed sensor engendered ∼2.5 fold larger electroactive surface area in comparison to bare GCE which substantially accelerated the rate of electron transfer via improved electrical conductivity. At optimal experimental conditions, oxidation current showed a wide linear response for ACV in the concentration range from 10 nM to 30 µM. The proposed sensor exhibited pronounced analytical performance for the determination of ACV with limit of detection corresponding to 1.8 nM and high sensitivity of 15.4 µA µM-1. The modified sensor showcased high recognition selectivity, fair reproducibility and long term stability of signal response in the physiological environment. The developed prototype was successfully implemented to quantify ACV in several commercially available pharmaceuticals. The versatile method described herein was efficaciously applied further in detecting ACV in real human urine sample of patient undergoing pharmacological treatment with ACV. The results explicitly demonstrate the applicability of the developed sensor in quality control, pharmacokinetic studies and clinical analysis.

39.2 VIRAL EXPOSURES AND SCHIZOPHRENIA

BackgroundEpidemiological, immunological, and microbiological studies indicate that infections with members of the family Herpesviridae may be associated with schizophrenia and with cognitive impairment. Herpesviruses are enveloped, double-stranded DNA viruses which are widely prevalent and which are capable of causing persistent infections. The most highly replicated association is that between the alpha herpesvirus Herpes Simplex Virus Type 1 (HSV-1) and cognitive impairment in schizophrenia. Acute HSV-1 infection results in oral lesions which usually resolve spontaneously. However, latency can occur in nerve root ganglia leading to cycles of reactivation in later life. Other herepsviruses may also be associated with schizophrenia. Epstein Barr virus (EBV) is a gamma herpesvirus usually acquired in childhood or adolescence. Acute EBV infection is often associated with fever and adenopathy leading to a vigorous immune response and the suppression of viral replication. However, latency can occur with long term consequences to the infected individual.MethodsWe examined the association between HSV-1 seropositivity and cognitive functioning in 828 individuals with schizophrenia from the Sheppard Pratt cohort and 573 control individuals. We also studied antibodies to EBV in a recently enrolled subset of the Sheppard Pratt cohort consisting of 397 individuals with schizophrenia and 289 without a psychiatric disorder. Antibodies to HSV-1 and EBV proteins were measured by immunoassay and confirmed by Western blot. Cognitive functioning was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regression models were employed to define the independent association between virus exposure and outcome.ResultsSerological evidence of exposure to HSV-1 was associated with significantly lower levels of cognitive functioning as measured by the RBANS Total score (coefficient =-3.84, 95% CI -5.60, -2.09, p<.0001). The strongest association was in the domain of Immediate Memory (coefficient= -4.95, 95% CI -7.24, -2.66, p<.0001.) There was a smaller but statistical significant relationship between serological evidence of exposure to HSV-1 and RBANS Total score in control individuals. (coefficient =-1.98, 95% CI -3.88, -.094, p=.04).In terms of EBV, we found that individuals with schizophrenia had significantly higher levels of antibodies to the EBV viral capsid antigens (VCA) as compared to controls (coefficient= .57, 95% CI .37- .77, p<1.7 10-8). On the other hand, the level of antibody to the EBV Nuclear Antigen (EBNA) and EBV Early Antigen (EA) did not differ between the groups. Within the schizophrenia group, increased levels of EBV VCA antibodies were associated with older age, female gender, and cigarette smoking but not with clinical or cognitive measures.DiscussionThe mechanism of the association between HSV-1 exposure and cognitive deficits in individuals with schizophrenia may be due to underlying neuroanatomical deficits, immune dysregulation, or gene x environmental interactions. The aberrant immune response to EBV may represent underlying immunopathy or exposure to variant viral strains. Other herpesviruses, such as Cytomegalovirus, Herpes Simplex Virus Type 2 and Human Herpesvirus Type 6 have also been associated with schizophrenia risk or with cognitive impairment in some populations. The prevention and treatment of herpesvirus infections might lead to new therapeutic modalities for schizophrenia.

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies.

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection.

Biophysical and In Silico Studies of the Interaction between the Anti-Viral Agents Acyclovir and Penciclovir, and Human Serum Albumin.

Acyclovir (ACV) and penciclovir (PNV) have been commonly used during the last few decades as potent antiviral agents, especially for the treatment of herpes virus infections. In the present research their binding properties with human serum albumin (HSA) were studied using different advanced spectroscopic and in-silico methods. The interactions between ACV/PNV and HSA at the three investigated temperatures revealed a static type of binding. Extraction of the thermodynamic parameters of the ACV-HSA and PNV-HSA systems from the measured spectrofluorimetric data demonstrated spontaneous interactions with an enthalpy change (∆H0) of −1.79 ± 0.29 and −4.47 ± 0.51 kJ·mol−1 for ACV and PNV, respectively. The entropy change (∆S0) of 79.40 ± 0.95 and 69.95 ± 1.69 J·mol−1·K−1 for ACV and PNV, respectively, hence supported a potential contribution of electrostatic binding forces to the ACV-HSA and PNV-HSA systems. Putative binding of ACV/PNV to HSA, using previously reported site markers, showed that ACV/PNV were bound to HSA within subdomains IIA and IIIA (Sudlow sites I and II). Further confirmation was obtained through molecular docking studies of ACV-HSA and PNV-HSA binding, which confirmed the binding site of ACV/PNV with the most stable configurations of ACV/PNV within the HSA. These ACV/PNV conformers were shown to have free energies of −25.61 and −22.01 kJ·mol−1 for ACV within the HSA sites I and II and −22.97 and −26.53 kJ·mol−1 for PNV in HSA sites I and II, with hydrogen bonding and electrostatic forces being the main binding forces in such conformers.

In vitro antiherpes effect of C-glycosyl flavonoid enriched fraction of Cecropia glaziovii encapsulated in PLGA nanoparticles

In this work is reported a novel and promising approach for the preparation of C-glycosylflavonoid enriched fraction of Cecropia glaziovii (EFF-Cg) loaded PLGA nanoparticles (NP) with antiherpes properties. The purpose of this study was to evaluate and to compare the effect of two nonionic surfactants (poloxamer 188 (PLU) and polyvinyl alcohol (PVA)), and also an emulsion stabilized by solid particles of cellulose nanocrystal (CNC) in place of surfactants. The characterization of these nanoparticles was in terms of size, polydispersity index, zeta potential, morphology, thermogravimetric analysis (TGA), loading capacity and percent yield. Since TGA analysis revealed thermo stability especially for NP-PLU, this formulation was selected for the evaluation of drug release profile, cytotoxicity and antiherpes activity. The drug delivery profile demonstrated a sustained release through the polymer structure and a significant reduction of the polymer molecular weight at 21-day period. The cytotoxicity of these nanoparticles was determined on Vero cells, and the selected formulation did not exhibit cytotoxicity even at the highest tested concentration. The results demonstrated a potential antiherpetic effect of the EFF-Cg loaded NP at 48h of testing. In summary, EFF-Cg loaded NP exhibited a promising system for the effective drug delivery in the treatment of herpes infections.

Development of the suppository form of human immunoglobulin preparation with high titers of antibodies to herpes simplex virus types 1 and 2 for the treatment of chronic forms of herpetic disease

In spite of the vast arsenal of therapeutic agents, therapy of herpes virus infection (HVI) is very difficult, particularly in pregnant women, newborns and children in the first years of life, as well as in patients with immune deficiency. In this regard, possibility of using immunoglobulins for the treatment of HVI is currently attracting the attention of doctors. The aim of this work was to develop a suppository form of the drug containing donor immunoglobulins with high levels of neutralizing antibodies to herpes simplex virus types 1 and 2 for the treatment of chronic forms of herpetic disease. The study included the following steps: 1) selection of gamma-globulins with high antibody titer for HSV-1 and HSV-2 ELISA test; 2) determination of the level of neutralizing antibodies in the selected series of gamma-globulins in tests in tissue cultures and animals; 3) lyophilization of immunoglobulins; 4) development of the suppository form of the preparation containing gamma-globulin donors with high levels of neutralizing antibodies to HSV-1 and HSV-2; 5) study of the safety of the activity of neutralizing antibodies to HSV-1 and HSV-2 in the suppository form of the drug with hyaluronic acid used as immunomodulator. As the result of this work, immunoglobulin preparation in the suppository form was developed. The developed preparation meets the requirements for safety and efficacy. It is not toxic or pyrogenic. The problems of clinical use of this drug as a method of HVI therapy are discussed.

Proteflazid®: clinical and economic substantiation for use in therapy of herpes infection

Epidemiological data indicate the widespread dissemination and constant dynamics of the incidence rate of herpesvirus infections due to a variety of forms and transmission paths of the virus, highly contagious and life-long persistence of the herpes virus in the body of the infected persons and the lack of effectiveness of existing treatments. Acyclic guanosine derivatives are the main group of antiviral drugs traditionally used for the causal treatment of herpes infections. They have a number of disadvantages, in particular formation of the virus resistance in a long-term use, the need to involve immunotherapy, as well as the high cost of treatment. The accumulated clinical experience with the original Ukrainian drug Proteflazid® (drops) in treating viral infections, including HHV- infections, shows its high clinical efficacy and safety. A relative estimation of the course treatment costs of herpes-induced infections using antiviral drugs has demonstrated the economic expediency of Proteflazid® with the purpose of treatment and maintenance therapy. Proteflazid® takes the medium sized niche among other antiherpetic drugs. In addition, due to the multi-vector nature of its pharmacodynamic effects (direct antiviral, immunomodulating, interferon-stimulating, antioxidant, apoptosis-modulating, etc.) Proteflazid® allows to exclude antioxidants, immunomodulators from the antiherpetic therapy scheme, or to adjust their use, and it can significantly reduce the cost per a course of treatment.

Effectiveness of the low-molecular inductor of interferon of Amiksin® in treatment and preventive maintenance of the chronic recurrent inflammatory diseases of the upper respiratory tract

Introduction. In the formation of recurrent and/or prolonged chronic inflammatory diseases of the upper respiratory tract in addition to the known, previously studied, factors that play an important role in the violation of the human immune system at the level of local (mucosal) and systemic immunity and activation of herpes virus group (Epstein Virus Barr virus, cytomegalovirus, herpes simplex virus type 6). In the treatment of herpesvirus infections, activation of antiviral immunity in domestic medicine used drugs interferon inducer. Objective. To evaluate the efficacy of interferon inductor Amiksin® in patients with chronic recurrent inflammatory diseases of the upper respiratory tract. Materials and methods. Based on separation of “Allergy and Immunotherapy” SSC “Institute of Immunology” FMBA studied low-molecular interferon inductor Amixin® (JSC “Pharmstandard-Tomskhimpharm”, Russia) in the treatment of chronic recurrent inflammatory diseases of the upper respiratory tract. The study included 40 patients between men and women, aged 18 to 65years old with a history of recurrent chronic inflammatory diseases of the upper respiratory tract. Clinical research methods included a medical history, previous efficiency of the treatment, the presence of comorbidities. Laboratory methods include bacteriological crop on flora in the material from the oropharynx and the detection of DNA viruses of herpes group in saliva. Patients of the main group, after clinical and laboratory examination, prescribed therapy with Amixin®. Patients in both groups received symptomatic therapy. The total duration of observation of each patient was 3 months. Results. Amiksin® receiving the drug in patients with acute exacerbation of chronic recurrent upper respiratory tract inflammatory diseases contributed to a more rapid relief of general and local symptoms. Also it found that reduces performance Amiksin® average viral load against Epstein-Barr virus. Over the next 3 months follow-up, 25 % of patients the main group marked exacerbation study pathology of the upper respiratory tract, in the control group of patients with recurrent exacerbations were more - 60 %, indicating that preventive action Amiksin® therapy. Conclusions: The use of low-molecular interferon inductor Amiksin®(JSC “Pharmstandard-Tomskhimpharm”, Russia) in the combined therapy showed good efficacy in reducing the concentration of chronic viral infections in the oropharynx and prevention of chronic relapsing inflammatory diseases of the upper respiratory tract.