The objective of this study is to provide a mechanistic insight into solubility enhancement and dissolution of acyclovir (ACY) by polyethylene glycol20000 (PEG20000).
The bioavailability of a generic preparation of acyclovir (Avorax) was compared with the innovator product, Zovirax. Twelve healthy volunteers participated in the study, conducted according to a randomized, two-way crossover design. The preparations were compared using the parameters area under the plasma concentration time curve (AUC(0-infinity), peak plasma concentration (Cmax), and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the Tmax or the logarithmic transformed AUC(0-infinity) and C(max) values of the two preparations. In addition, the 90% confidence interval for the ratio of the logarithmic transformed AUC(0-infinity) values of Avorax over those of Zovirax was found to lie between 0.85 and 1.06, while that of the logarithmic transformed Cmax values was between 0.95 and 1.25, being within the bioequivalence limit of 0.80-1.25. Moreover, the elimination rate constant (k(e)), elimination half-life (t(1/2)), and apparent volume of distribution (Vd) values obtained with the two preparations were comparable and not significantly different statistically.
Bell palsy is a non-progressive neurological condition characterized by the acute onset of ipsilateral seventh cranial nerve paralysis. People who suffer from this type of facial paralysis develop a droop on one side of their face, or sometimes both. This condition is distinguished by a sudden onset of facial paralysis accompanied by clinical features such as mild fever, postauricular pain, dysgeusia, hyperacusis, facial changes, and drooling or dry eyes. Epidemiological evidence suggests that 15 to 23 people per 100,000 are affected each year, with a recurrence rate of 12%. It could be caused by ischaemic compression of the seventh cranial nerve, which could be caused by viral inflammation. Pregnant women, people with diabetes, and people with respiratory infections are more likely to have facial paralysis than the general population. Immune, viral, and ischemic pathways are all thought to play a role in the development of Bell paralysis, but the exact cause is unknown. However, there is evidence that Bell's hereditary proclivity to cause paralysis is a public health issue that has a greater impact on patients and their families. Delay or untreated Bell paralysis may contribute to an increased risk of facial impairment, as well as a negative impact on the patient's quality of life. For management, antiviral agents such as acyclovir and valacyclovir, and steroid treatment are recommended. Thus, early diagnosis accompanied by treatment of the uncertain etiology of the disorder is crucial. This paper reviews mechanistic approaches, and emerging medical perspectives on recent developments that encounter Bell palsy disorder.
A micellar electrokinetic chromatography (MEKC) method for the simultaneous determination of the antiviral drugs acyclovir and valacyclovir and their major impurity, guanine, was developed. The influences of several factors (surfactant and buffer concentration, pH, applied voltage, capillary temperature and injection time) were studied. Using tyramine hydrochloride as internal standard, the analytes were all separated in about 4 min. The separation was carried out in reversed polarity mode at 28 degrees C, 25 kV and using hydrodynamic injection (15 s). The separation was effected in a fused-silica capillary 100 microm x 56 cm and a background electrolyte of 20 mM citric acid-1 M Tris solution (pH 2.75), containing 125 mM sodium dodecyl sulphate and detection at 254 nm. The method was validated with respect to linearity, limit of detection and quantification, accuracy, precision and selectivity. Calibration curves were linear over the range 0.1-1 microg/mL (guanine) and from 0.1 to 120 microg/mL for both valacyclovir and acyclovir. The relative standard deviations of intra- and inter-day migration times and corrected peak areas were less than 5.0%. The proposed method was successfully applied to the determination of the analytes in tablets and creams. From the previous study it is concluded that the stability-indicating method developed for acyclovir and valacyclovir can be used for analysis of the drug in various stability samples.
We report a case of Japanese encephalitis that occurred in a woman who had spent only a few days in an area where she could have been exposed to the virus. The risks and protective efficacy of vaccination against Japanese encephalitis virus for travellers who visit endemic areas for only a short period are discussed.
Matched MeSH terms: Acyclovir/administration & dosage; Acyclovir/therapeutic use
A simple high-performance liquid chromatographic method using fluorescence detection was developed for the determination of acyclovir in human plasma. The method entailed direct injection of the plasma sample after deproteination. It is both specific and sensitive with a detection limit of 30 ng/ml at a signal-to-noise ratio of 3:1, and is thus suitable for use in pharmacokinetic studies of acyclovir. The method had a mean absolute recovery of 96%, while the within-day and between-day coefficients of variation and percentages error were all less than 8%. The calibration curve was linear over a concentration range of 62.5-4000 ng/ml.
This study conducted on the structure of modified acrylamide-based hydrogel by synthesizing the nano composites. The hydrogels employed in this study were provided through a combination of acrylamide monomers, sodium carboxymethyl cellulose (NaCMC) and magnesium oxide (MgO) nanoparticles by crosslinking polymerization. N,N,N',N'-tetramethylethylenediamine and ammonium persulfate as the initiator was applied in the structure of the polymer. Findings of the study considered the nano composites consisting of MgO have the highest swelling ratio compared to pure Aam hydrogels. Thus, MgO is an appropriate nanoparticle to be used in the nano composites. Response surface methodology (RSM) based on a central composite design (CCD Design) was applied to optimize the preparation variables of a hydrogel consisted of MgO, NaCMC. With the swelling ratio for acrylamide-based hydrogel as the response, the effects of two variables, i.e. MgO and NaCMC were investigated. The effects of pH, temperature, MgO, and NaCMC on the drug release were investigated using the CCD design. The predicted appropriate drug release conditions for the hydrogel at the highest rate of temperature (37.50 °C) and pH: 4.10, is at its highest value, while the lower drug release is at temperature 38 °C and pH 3.50. With the desired value of MgO (0.01 g) and amount of NaCMC (0.1 g).
Currently, pharmaceutical research is directed wide range for developing new drugs for oral administration to target disease. Acyclovir formulation is having common issues of short half-life and poor permeability, causing messy treatment which results in patient incompliance. The present study formulates a lipid polymeric hybrid nanoparticles for antiviral acyclovir (ACV) agent with Phospholipon® 90G (lecithin), chitosan, and polyethylene glycol (PEG) to improve controlled release of the drugs. The study focused on the encapsulation of the ACV in lipid polymeric particle and their sustained delivery. The formulation developed for the self-assembly of chitosan and lecithin to form a shell encapsulating acyclovir, followed by PEGylation. Optimisation was performed via Box-Behnken Design (BBD), forming nanoparticles with size of 187.7 ± 3.75 nm, 83.81 ± 1.93% drug-entrapped efficiency (EE), and + 37.7 ± 1.16 mV zeta potential. Scanning electron microscopy and transmission electron microscopy images displayed spherical nanoparticles formation. Encapsulation of ACV and complexity with other physical parameters are confirmed through analysis using Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. Nanoparticle produced was capable of achieving 24-h sustained release in vitro on gastric and intestinal environments. Ex vivo study proved the improvement of acyclovir's apparent permeability from 2 × 10-6 to 6.46 × 10-6 cm s-1. Acyclovir new formulation was achieved to be stable up to 60 days for controlled release of the drugs. Graphical abstract.
This is a retrospective study. The objective of this study is to review the factors influencing the outcome of treatment for the patients presented with idiopathic facial nerve paralysis. The demographic data, clinical presentation and management of 84 patients with idiopathic facial nerve paralysis (Bell's palsy) were collected from the medical record office, reviewed and analyzed from 2000 to 2005. Thirty-four (72.3%) out of 47 patients who were treated with oral prednisolone alone, fully recovered from Bell's palsy meanwhile 36 (97%) out of 37 patients who were treated with combination of oral prednisolone and acyclovir fully recovered. The difference was statistically significant. 42 (93.3%) out of 45 patients who presented within three days to our clinic, fully recovered while 28 (71.8%) out of 39 patients presented later then three days had full recovery from Bell's palsy. The difference was statistically significant. The outcome of full recovery is better with the patients treated with combined acyclovir and prednisolone compared with prednisolone alone. The patients who were treated after three days of clinical presentation, who were more than 50 years of age, who had concurrent chronic medical illness and facial nerve paralysis HB Grade IV to VI during initial presentation have reduced chance of full recovery of facial nerve paralysis.
We describe a case of adult chickenpox which was complicated by severe varicella pneumonia, mild hepatitis and thrombocytopenia. The hepatitis and the thrombocytopenia were asymptomatic clinically and were diagnosed on biochemistry and blood count results. These eventually improved without specific interventions. The pneumonia, however, deteriorated rapidly despite the early commencement of oxygen supplementation, acyclovir and antibiotic. Subsequently, systemic corticosteroid therapy was initiated and the patient was ventilated in the intensive care unit. The patient eventually recovered.
Bell's palsy is a benign lower motor neuron facial nerve disorder. It is almost always unilateral. We report a 20-year-old nulliparous woman with five episodes of recurrent Bell's palsy. A review of recent medical literature revealed a paucity of case reports involving an individual with five episodes of recurrent Bell's palsy, with none found in Asian neurology medical literature. Despite the multiple episodes of Bell's palsy recurrences, the patient did not suffer much neurological sequelae from the disease.
Introduction:Acyclovir, a widely marketed antiviral drug is used for the treatment of Herpes Simplex infection. High doses of acyclovir are prescribed to patients to attain its maximum therapeutic effect due to its poor absorption and low oral bioavailability. The current therapeutics regiment of acyclovir are known to cause unwarranted adverse effects, thus prompted the need for a suitable drug carrier to improve the pharmacokinetic limitations. Develop-ment of solid lipid nanoparticles for oral delivery of acyclovir proposed in this study aimed to enhance acyclovir oral bioavailability. Methods: Comprehensive experiments and a series of optimization process were carried out to ensure reproducibility and assurance of product quality. The physicochemical characteristics of the solid lipid nanoparticles developed from plant-based solid lipid, Biogapress Vegetal 297 ATO with polysorbate 80 as an emul-sifying agent were also evaluated. Results: The spherical-shaped nanoparticles had an average size of 123 nm with good drug entrapment efficiency, up to 80%. The in vitro drug release study showed that solid lipid nanoparticles had prolonged acyclovir release in simulated intestinal fluid for 24 hours. The nanoparticles formulation was con-sidered stable during storage at refrigerated temperature for at least three months. In vivo oral bioavailability study showed that acyclovir-loaded solid lipid nanoparticles possessed superior oral bioavailability when compared with the commercial acyclovir suspension. Conclusion: In conclusion, this study exhibited the feasibility of solid lipid nanoparticles as an oral delivery vehicle for acyclovir and therefore represent a new promising therapeutic concept of nanoparticulate delivery system.
Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral bioavailability is low; therefore, frequent and high doses are prescribed for optimum therapeutic efficacy. Moreover, the current therapeutic regimen of acyclovir is associated with unwarranted adverse effects, hence prompting the need for a suitable drug carrier to overcome these limitations. This study aimed to develop solid lipid nanoparticles (SLNs) as acyclovir carriers and evaluate their in vivo pharmacokinetic parameters to prove the study hypothesis. During the SLN development process, response surface methodology was exploited to optimize the composition of solid lipid and surfactant. Optimum combination of Biogapress Vegetal 297 ATO and Tween 80 was found essential to produce SLNs of 134 nm. The oral bioavailability study showed that acyclovir-loaded SLNs possessed superior oral bioavailability when compared with the commercial acyclovir suspension. The plasma concentration of acyclovir-loaded SLNs was four-fold higher than the commercial suspension. Thus, this investigation presented promising results that the method developed for encapsulation of acyclovir offers potential as an alternative pathway to enhance the drug's bioavailability. In conclusion, this study exhibited the feasibility of SLNs as an oral delivery vehicle for acyclovir and therefore represents a new promising therapeutic concept of acyclovir treatment via a nanoparticulate drug delivery system.
To report a rare case of an elderly gentleman who presented with herpes zoster ophthalmicus, complicated with persistent hyphema and orbital apex syndrome. A 75-year-old Malay gentleman presented with left herpes zoster ophthalmicus that was complicated with complete ophthalmoplegia and ptosis. He developed total hyphema in the affected eye with a secondary elevated intraocular pressure after a week. He was treated with oral acyclovir and topical corticosteroids. However, the total hyphema persisted that required an anterior chamber washout surgery. Herpes Zoster Ophthalmicus complicated with persistent hyphema and orbital apex syndrome is rare and very challenging to manage. Radiological imaging is important to exclude other causes of OAS. It is recommended to treat HZO with systemic acyclovir for a longer duration in view of ocular and neurological involvement.
Eleven strains of acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) were generated from HSV-1 clinical isolates by exposure to ACV. Genotype of the thymidine kinase (TK) and DNA polymerase (pol) genes from these mutants were further analyzed. Genotypic analysis revealed four non-synonymous mutations in TK gene associated with gene polymorphism and two to three non-synonymous mutations in DNA pol gene. Seven and six strains contained at least one resistance-associated mutation at TK and DNA pol gene, respectively. Resistance-associated mutations within the TK gene consisted of 64% of non-synonymous frameshift mutations within the homopolymer region of G's and C's, and 36% of non-synonymous nucleotide substitutions of the conserved gene region (C336Y, R51W and R222H), nucleotide that produced stop codon (L288Stop) and two amino acid substitutions outside the conserved region (E39G & L208F). There were 10 non-synonymous amino acid substitutions located outside the conserved region with the unclear significance to confer resistance observed. Resistance-associated mutations in DNA pol gene include insertion of G at the homopolymer region of G's (794-797) and amino acid substitutions inside (V621S) or outside (H1228D) the conserved region. In silico analysis of the mutated TK (C336Y, R51W and L208F), and DNA pol (V621S and H1228D) suggested structural changes that might alter the stability of these proteins. However, there were several mutations with unclear significance to confer ACV-resistance identified, especially mutations outside the conserved region.
Acute retinal necrosis (ARN) is known to occur in conjunction with primary varicella or chickenpox infection. The majority of ARN cases reported in the literature were of milder form with mild to moderate vitritis, limited retinitis, and rare occurrence of retinal breaks or detachment that responded well to intravenous acyclovir, with or without oral prednisolone. We report a case of unilateral ARN with marked vitritis and retinal necrosis leading to retinal breaks following chickenpox in a 32-year-old healthy lady. This patient was successfully treated with intravenous acyclovir followed by oral acyclovir and orbital floor triamcinolone injections to contain the inflammation with barrier laser therapy to secure the retinal breaks with good visual outcome. This case is unusual in its severity, and to our knowledge, orbital floor triamcinolone therapy was not used earlier to contain ARN inflammation.
Introduction: Varicella pneumonitis is a rare but lethal complication of varicella zoster infection. Case description:We report a case of a 42 year old gentleman who presented with fever, rash, cough and worsening shortness of breath after exposure to his daughter who just recovered from varicella zoster infection. He is an active smoker with no comorbidities. He presented on day 4 of illness with generalised vesicular eruption and respiratory examination revealed reduced vesicular breath sounds bilaterally. He was intubated in view of worsening respiratory distress and was transferred to ICU. Chest X-ray and ABG was suggestive of acute respiratory distress syndrome(ARDS). He was treated with IV Acyclovir and broad spectrum antibiotics in view of subsequent hospital acquired infection. He was discharged well after 3 weeks of hospitalisation. Discussion: Varicella zoster infection is caused by Human alpha-herpesvirus 3, one of eight herpes viruses known to infect humans. Diagnosis of varicella pneumonitis with ARDS was made on the basis of rash, respiratory symptoms and contact with a child who just recovered from varicella zoster infection and rapid worsening of radiological changes. The risk factor of developing severe pneumonitis can be attributed to active smoking. Conclusion: High degree of suspicion and timely diagnosis is crucial for a favourable outcome in a patient with this rare complication.
Acute retinal necrosis (ARN) is a rare, blinding disease that typically affects adults. However, in this case report, we highlight the diagnosis, management and outcome of herpes simplex acute retinal necrosis in a 13-year-old healthy girl, who presented with painful right eye, redness and blurring of vision for one week. Examination of the right eye showed features of granulomatous panuveitis. Optic disc was swollen and retina appeared pale. There were multiple patches of retinitis and haemorrhages at mid-periphery of the fundus with inferior serous detachment observed. Rapidly progressive inflammation in just four days along with secondary cataract that obscured fundus view, imposed greater challenge to the diagnosis and management. Intravenous acyclovir 300mg, 3 times a day was initiated promptly while vitreous fluid was sent for polymerase chain reaction, which identified Herpes Simplex Virus-1. Inflammation improved, but she developed vitreous haemorrhage secondary to proliferative retinopathy, which required panretinal photocoagulation. ARN is therefore, principally a clinical diagnosis and high index of suspicion is crucial particularly, in children for prompt diagnosis and treatment. Complications should also be addressed timely to improve the chances of preserving vision.
The transdermal delivery of sparingly soluble drugs is challenging due to of the need for a drug carrier. In the past few decades, ionic liquid (IL)-in-oil microemulsions (IL/O MEs) have been developed as potential carriers. By focusing on biocompatibility, we report on an IL/O ME that is designed to enhance the solubility and transdermal delivery of the sparingly soluble drug, acyclovir. The prepared MEs were composed of a hydrophilic IL (choline formate, choline lactate, or choline propionate) as the non-aqueous polar phase and a surface-active IL (choline oleate) as the surfactant in combination with sorbitan laurate in a continuous oil phase. The selected ILs were all biologically active ions. Optimized pseudo ternary phase diagrams indicated the MEs formed thermodynamically stable, spherically shaped, and nano-sized (<100 nm) droplets. An in vitro drug permeation study, using pig skin, showed the significantly enhanced permeation of acyclovir using the ME. A Fourier transform infrared spectroscopy study showed a reduction of the skin barrier function with the ME. Finally, a skin irritation study showed a high cell survival rate (>90%) with the ME compared with Dulbecco's phosphate-buffered saline, indicates the biocompatibility of the ME. Therefore, we conclude that IL/O ME may be a promising nano-carrier for the transdermal delivery of sparingly soluble drugs.
This study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus, Synechococcus elongatus, and Spirulina platensis against Epstein-Barr virus (EBV) in three Burkitt's lymphoma (BL) cell lines, namely Akata, B95-8, and P3HR-1. The antiviral activity was assessed by quantifying the cell-free EBV DNA using real-time polymerase chain reaction (PCR) technique. The methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in reducing cell-free EBV DNA (EC(50)<0.01 µg/ml) with a high therapeutic index (>28000). After fractionation by column chromatography, the fraction from Synechococcus elongatus (SEF1) reduced the cell-free EBV DNA most effectively (EC(50)=2.9 µg/ml, therapeutic index>69). Upon further fractionation by high performance liquid chromatography (HPLC), the sub-fraction SEF1'a was most active in reducing the cell-free EBV DNA (EC(50)=1.38 µg/ml, therapeutic index>14.5). This study suggests that microalgae could be a potential source of antiviral compounds that can be used against EBV.