Topical application of acyclovir-loaded microparticles: quantification of the drug in porcine skin layers (original) (raw)
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AAPS PharmSciTech, 2009
The present investigation aims at developing microemulsion-based formulations for topical delivery of acyclovir. Various microemulsions were developed using isopropyl myristate/Captex 355/ Labrafac as an oil phase, Tween 20 as surfactant, Span 20 as cosurfactant, and water/dimethylsulfoxide (1:3) as an aqueous phase. Transcutol, eucalyptus oil, and peppermint oil were used as permeation enhancers. In vitro permeation studies through laca mice skin were performed using Franz diffusion cells. The optimum formulation containing 2.5% Transcutol as the penetration enhancer showed 1.7-fold enhancement in flux and permeation coefficient as compared to marketed cream and ointment formulation. In vivo antiviral studies were performed in female Balb/c mice against induced herpes simplex virus I infection. A single application of microemulsion formulation containing 2.5% Transcutol given 24 h post-injection resulted in complete suppression of development of herpetic skin lesions.
European Journal of Pharmaceutics and Biopharmaceutics, 2003
Acyclovir is one of the most effective and selective agents against viruses of the herpes group. In order to increase its antiviral activity, acyclovir loaded microparticles, prepared by an O/W solvent evaporation method were developed. Their antiviral activity against herpes simplex virus type 1 (HSV-1) and toxicity were evaluated on Vero cells and then compared with those presented by a drug solution. The 50% inhibitory concentration (IC 50 ) values for acyclovir loaded microspheres determined by plaque reduction assays at 48 and 96 h, were found to be 1.06^0.01 mM and 0.15^0.03 mM, respectively, while the equivalent values obtained for an acyclovir solution were 1.28^0.04 mM at 48 h and 0.27^0.02 mM at 96 h. These results indicate that acyclovir shows a higher antiviral activity, against herpes simplex virus type 1, when this drug was loaded in microparticles rather than as a drug solution, especially after 96 h of incubation. The toxicity of these microparticles was determined by the MTT test at 48 and 96 h. At 48 h only a small toxicity was found (cell viability ranged from 72 to 82%, with the higher concentration tested) and it could not be attributed to the microparticles, since the acyclovir control solution showed similar toxicity values. However, after 96 h a higher toxicity was observed with acyclovir microparticles as well as with the unloaded ones (cell viability located between 60 and 70%). In summary, acyclovir-loaded microparticles have shown to be promising carriers for the effective delivery of acyclovir in the treatment of HSV-1 infections in cells so they can have a potential use in vivo. q
BMC Dermatology, 2009
Background: Herpes simplex virus infection (HSV) is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis) or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the in vitro skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores), using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm 2 of acyclovir 5% cream or penciclovir 1% cream. Methods: After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physicochemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips. Results: Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells. Conclusion: Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of penciclovir through the epidermis into the deeper basal cells.
The microsponge delivery system of Acyclovir:Preparation, characterization and in-vitro evaluation
2011
The aim of the present study was to develop and evaluate microsponge based topical delivery system of acyclovir for sustained and enhanced drug deposition in the skin. Microsponges containing acyclovir were prepared by an emulsion solvent diffusion method. The effect of formulation variable such as drug: polymer ratio, stirring speed, internal phase on the physical characteristics of microsponges were analyzed in order to optimize the formulation. These two microsponge formulation were prepared as gel in 0.35 %w/w carbopol and studied for pH, viscosity, spreadability, drug content, and in vitro release. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. The formulations were subjected to in vitro release studies and the results were evaluated kinetically and statistically. Developed microsponges were spherical and porous, and there was no interaction between drug and polymer molecules. Drug release through cellulose dialysis membrane s...
Enhanced dermal delivery of acyclovir using solid lipid nanoparticles
The present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir (ACV) and evaluate their potential as the carrier for dermal delivery. ACV-loaded SLNs (ACV-SLNs) were prepared by the optimized double emulsion process using Compritol 888 ATO as solid lipid. The prepared SLNs were smooth and spherical in shape with average diameter, polydispersity index, and entrapment efficiency of 262 ± 13 nm, 0.280 ± 0.01, and 40.08 ± 4.39% at 10% (w/w) theoretical drug loading with respect to Compritol 888 ATO content. Differential scanning calorimetry and powder X-ray diffraction pattern revealed that ACV was present in the amorphous state inside the SLNs. In vitro skin permeation studies on human cadaver and Sprague–Dawley rat skin revealed 17.65 and 15.17 times higher accumulation of ACV-SLNs in the dermal tissues in comparison to commercially available ACV cream after 24 h. Mechanism of topical permeation and dermal distribution was studied qualitatively using confocal laser scanning microscopy. While free dye (calcein) failed to penetrate skin barrier, the same encapsulated in SLNs penetrated deeply into the dermal tissue suggesting that pilosebaceous route was followed by SLNs for skin penetration. Histological examination and transdermal epidermal water loss measurement suggested that no major morphological changes occurred on rat skin surface due to the application of SLNs. Overall, it was concluded that ACV-loaded SLNs might be beneficial in improving dermal delivery of antiviral agent(s) for the treatment of topical herpes simplex infection.
Formulation And Evaluation Of Acyclovir Sodium Solid Lipid Microparticles
American Journal of Advanced Drug Delivery, 2016
Acyclovir sodium is an antiviral drug used to treat herpes, chicken pox and herpes skin infections. Acyclovir sodium potential as an antiviral drug is limited by its low oral bioavailability (20-30%) with short half-life (2-3 hours) with poor plasma protein binding. There is an opportunity to utilize Acyclovir sodium as an antiviral drug by enhancing the bioavailability by formulation technology. In this paper solid microparticle (o/w) of Acyclovir was prepared by melt dispersion technique. The characterization of drug using scanning electron microscopy, FT-IR, particle size, percentage yield, drug loading capacity, hausner's ratio and carr's index, bulk density and tapped density. In vitro drug release studies using phosphate buffer has shown as formulation F5 sustained release for 17 hrs.
International journal of pharmaceutics, 2004
The aim of this study was to characterize and compare the pharmacokinetics of acyclovir (ACV) in skin and plasma after iontophoresis, i.v.-bolus, and ointment administrations in rabbit. On five occasions, each separated by at least 1-week washout, rabbits received a 10 mg/kg dose of ACV as i.v.-bolus, ACV iontophoresis for 1 h at different current densities (100, 200, 300 microA/cm2) or a commercially available ointment for two hours. Blood samples were collected serially up to 6 h. Skin ACV concentrations were monitored via microdialysis using linear microdialysis probes (1 cm window). Cathodic iontophoresis was performed using commercially available patches (10 cm2 contact area). Following i.v.-bolus, C(max) in skin occurred with a delay of 38 +/- 4 min compared with plasma. No quantifiable concentration of ACV was detected in the skin on passive drug delivery. Following iontophoresis, skin exposure to ACV was 40, 22, and 11% of that following i.v.-bolus. Conversely, systemic expo...
Quantification of uptake and clearance of acyclovir in skin layers
Antiviral Therapy, 2015
Background Quantification of drug uptake and clearance in the skin layers could provide better insight into the skin kinetics of dermatological formulations aimed for deeper skin tissues. This study assessed the skin kinetics of acyclovir in different skin layers following topical application on the abdominal region of Wistar rats. Methods In vivo skin pharmacokinetics parameters were determined by two different protocols such as post drug load assessment and subsequent drug load assessment following topical application of 500 mg of cream formulation containing 5% (w/w) of acyclovir. Results Topical application of acyclovir exhibited concentration gradient between the skin layers (stratum corneum > viable epidermis > dermis) which were inconsistent over the time-course of the study. The rate and extent of drug reaching target site (basal epidermis) was relatively low. The drug uptake and clearance pro-files were found to be distinct in all the three skin layers suggesting no d...
Objective of present work was to formulate polymeric microparticles of acyclovir using β-cyclodextrin by solvent evaporation method and kneading technique. Four different ratios were fabricated in each case. Sodium lauryl sulfate (4%) was utilized as intestinal permeation enhancer in this study. Prepared microparticles were characterized for micromeritic properties i.e., angle of repose, Hausnerís ratio, Carrís index, bulk density and tapped density, entrapment efficiency, zeta size and zeta potential, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction, scanning electron microscopy, transmission electron microscopy, optical microscopy and permeability studies across chicken intestine. Kinetic mod- els: zero order, first order, Higuchi and Korsmeyer Peppas were applied on release data. Based upon the results of entrapment efficiency (81.25% and 74.50%), product yield (92.50% and 85.50%), permeability (85.18% and 82.05%), x-ray diffraction (amorphous nature), and solubility etc., (1 : 2) drug-polymer ratio was declared the best. Moreover, solid dispersions (1 : 2) had shown promising results. A new potential approach for solubility, bioavailability and permeability enhancement of acyclovir and other BCS class IV drugs was successfully established.