Delivery Of Acyclovir Research Articles

Formulating Spray-Dried Albumin-Modified Lipid Nanoparticles Encapsulating Acyclovir for Enhanced Pulmonary Drug Delivery.

Viral pneumonia, a pressing global health issue, necessitates innovative therapeutic approaches. Acyclovir, a potent ring-opening antiviral agent with broad-spectrum activity, faces water solubility, oral bioavailability, and drug resistance challenges. The aim of this study was to increase the efficacy of acyclovir through respiratory delivery by encapsulating it within albumin-modified lipid nanoparticles and formulate it as a spray. Nanoparticles was synthesized via the reverse evaporation method; its physicochemical characteristics were rigorously evaluated, including particle size, zeta potential, morphology, encapsulation efficiency, drug loading, and release profile. Furthermore, the cytotoxicity of nanoparticles and its therapeutic potential against viral pneumonia were assessed through cellular and animal model experiments. Result s: Nanoparticles exhibited a spherical morphology, with a mean particle size of 97.48 ± 5.36 nm and a zeta potential of 30.28 ± 4.72 mv; they demonstrated high encapsulation efficiency (93.26 ± 3.27%), drug loading (11.36 ± 0.48%), and a sustained release profile of up to 92% under neutral conditions. Notably, nanoparticles showed low cytotoxicity and efficient intracellular delivery of acyclovir. In vitro studies revealed that nanoparticles significantly reduced interleukin-6 levels induced by influenza virus stimulation. In vivo, nanoparticles treatment markedly decreased mortality, attenuated the inflammatory markers interleukin-6 and tumor necrosis factor-α levels, and mitigated inflammatory lung injury in mice with viral pneumonia. In this study, albumin was modified with polyethylene glycol (PEG) containing cationic lipid nanoparticles (LN) to prepare albumin-modified lipid nanoparticles encapsulating acyclovir (ALN-Acy), which can effectively deliver Acy into tissues and cells, prolong the survival of mice, and reduce lung injury and inflammatory factors. White albumin LN can be used as efficient drug delivery carriers, and the delivery of Acy via albumin LN is expected to be a therapeutic strategy for treating inflammatory diseases.

Formulation and Evaluation of Acyclovir Loaded Transferosomal Gel for Transdermal Drug Delivery

Background: A carrying structure for targeted transdermal drug delivery is a transferosome. These unique liposomes are made of an edge activator and phosphatidylcholine. The most common antiviral drug is acyclovir, a synthetic nucleotide nucleoside analog derived from guanine. It works well to cure the varicella-zoster virus and the virus that causes herpes simplex (HSV), primarily HSV-1 and HSV-2. But its skin permeability is minimal. Therefore, this work aimed to use transferosomes to prepare acyclovir so that it could pass through the skin's barrier function. Objective: This study uses a 32-factorial factorial design to develop a transferosomal gel containing acyclovir through thin-film hydration method for painless acyclovir delivery services for skin disease treatment. Material and Methods: The independent variables are the amount of phospholipid (X1) and tween 80 (X2), while the dependent variables are particle size (Y1) and percentage entrapment efficiency (Y2). To create an ideal formulation, the produced transferosomes were assessed for particle size, in vitro drug release amount, and entrapment efficiency (EE%). A Carbopol 934 gel basis was prepared using the optimized acyclovir transferosome formulation, and its drug concentration, pH, spreadability, viscosity, and stability were assessed. Results: With small particles ranging from 176.6 to 324.4 nm, the produced acyclovir transferosomes had a high EE% range from 66.34 to 76.42 %. According to the in vitro release study, there is a negative correlation between in vitro release and EE%. The formulation TF5, including 1%w/w of carbopol 940, provides a superior profile of drug absorption in vitro. Consequently, acyclovir can enter the skin as transferosomes and cross the stratum corneum barrier. Conclusion: Acyclovir can be transformed into a transfersomal gel, which will improve antiviral efficacy, get over the skin's protective layer, prevent adverse oral reactions, and eventually improve patient adherence. Keywords: Transferosome, Transdermal drug delivery system, Acyclovir, 32 Fractional factorial design, Carbopol 934

Development and characterization of stimuli responsive quince gum/β-CD grafted poly (methacrylate) hydrogels for controlled delivery of acyclovir

Development and characterization of stimuli responsive quince gum/β-CD grafted poly (methacrylate) hydrogels for controlled delivery of acyclovir

Detailed pharmacokinetic characterization of advanced topical acyclovir formulations with IVPT and in vivo Open Flow Microperfusion

Successful treatment of herpes simplex viruses is currently limited by a lack of effective topical drugs. Commonly used topical acyclovir products only reduce the duration of lesions by a few days. Optimizing topical formulations to achieve an enhanced acyclovir solubility and penetration could increase the efficacy of topically applied acyclovir, but new formulations need to show reliable acyclovir delivery into at least the epidermis/dermis and need to provide sustained acyclovir release for extended time periods. The aim of this study was to compare pharmacokinetic data from in vitro permeation testing (IVPT) and preclinical dermal open flow microperfusion (dOFM) experiments regarding the penetration behavior of different acyclovir formulations relative to the reference product Zovirax® 5% cream. Four test formulations that delivered the best penetration data in IVPT were further tested using continuous dOFM in vivo dermal sampling. The use of dOFM identified one of the four tested formulations to perform significantly better than the other three tested formulations and the reference product. In vivo dOFM data showed differences in the dermal acyclovir concentration that had not been detected by using IVPT. Improved acyclovir delivery to the dermis was likely achieved by the new formulation that uses a much lower drug load compared to the reference product. This optimized formulation was able to achieve a dermal concentration similar to oral application and can thus provide the opportunity of more efficacious topical HSV-1 treatment with less side effects than oral systemic treatment.

Preparation and Characterization of Poly(vinyl acetate-co-2-hydroxyethyl methacrylate) and In Vitro Application as Contact Lens for Acyclovir Delivery.

A series of poly(vinyl acetate-co-2-hydroxyethylmethacrylate)/acyclovir drug carrier systems (HEMAVAC) containing different acyclovir contents was prepared through bulk free radical polymerization of 2-hydroxyethyl methacrylate with vinyl acetate (VAc) in presence of acyclovir (ACVR) as the drug using a LED lamp in presence of camphorquinone as the photoinitiator. The structure of the drug carrier system was confirmed by FTIR and 1HNMR analysis, and the uniform dispersion of the drug particles in the carrier was proved by DSC and XRD analysis. The study of the physico-chemical properties of the prepared materials, such as the transparency, swelling capacity, wettability and optical refraction, was carried out by UV-visible analysis, a swelling test and measurement of the contact angle and the refractive index, respectively. The elastic modulus and the yield strength of the wet prepared materials were examined by dynamic mechanical analysis. The cytotoxicity of the prepared materials and cell adhesion on these systems were studied by LDH assay and the MTT test, respectively. The results obtained were comparable to those of standard lenses with a transparency of 76.90-89.51%, a swelling capacity of 42.23-81.80% by weight, a wettability of 75.95-89.04°, a refractive index of 1.4301-1.4526 and a modulus of elasticity of 0.67-1.50 MPa, depending on the ACVR content. It was also shown that these materials exhibit no significant cytotoxicity; on the other hand, they show significant cell adhesion. The in vitro dynamic release of ACVR in water revealed that the HEMAVAC drug carrier can consistently deliver uniformly adequate amounts of ACVR (5.04-36 wt%) over a long period (7 days) in two steps. It was also found that the solubility of ACVR obtained from the release process was improved by 1.4 times that obtained by direct solubility of the drug in powder form at the same temperature.

Fabrication and Preliminary Assessment of Neem Fruit Mucilage as Mucoadhesive Abetting Assets with Methpol-934P for Acyclovir Delivery from Mucoadhesive Microcapsules

In this study, we investigated the mucoadhesive properties of neem fruit mucilage by incorporating it into mucoadhesive microcapsules with Acyclovir (ACR). Methpol-934P and Neem fruit mucilage (NFM) was used to construct 12 different mucoadhesive microcapsules. We assessed FTIR and DSC capabilities for compatibility with ACR and NFM. ACR mucoadhesive microcapsules (ANMM) were characterized for mucoadhesion and ACR release Physico-chemical characteristics. CR was found to be compatible with NFM in the research. The entrapment increased as the levels of NFM in the formulations increased, and mucoadhesion time was longer in formulations with higher levels of NFM. As levels of NFM increase in formulations, the release of drugs is slightly reduced. NFM may be responsible for this due to its release retarding properties. An additive of neem fruit mucilage allowed for the retention of ACR after ingestion when a mucoadhesive polymer (methpol 934P) was used.

Development and Optimization of Tamarind Gum-β-Cyclodextrin-g-Poly(Methacrylate) pH-Responsive Hydrogels for Sustained Delivery of Acyclovir.

Acyclovir has a short half-life and offers poor bioavailability. Its daily dose is 200 mg five times a day. A tamarind gum and β-cyclodextrin-based pH-responsive hydrogel network for sustained delivery of acyclovir was developed using the free-radical polymerization technique. Developed networks were characterized by FTIR, DSC, TGA, PXRD, EDX, and SEM. The effect of varying feed ratios of polymers, monomers, and crosslinker on the gel fraction, swelling, and release was also investigated. FTIR findings confirmed the compatibility of the ingredients in a new complex polymer. The thermal stability of acyclovir was increased within the newly synthesized polymer. SEM photomicrographs confirmed the porous texture of hydrogels. The gel fraction was improved (from 90.12% to 98.12%) with increased reactant concentrations. The pH of the dissolution medium and the reactant contents affected swelling dynamics and acyclovir release from the developed carrier system. Based on the R2 value, the best-fit model was zero-order kinetics with non-Fickian diffusion as a release mechanism. The biocompatibility of the developed network was confirmed through hematology, LFT, RFT, lipid profile, and histopathological examinations. No sign of pathology, necrosis, or abrasion was observed. Thus, a pH-responsive and biocompatible polymeric system was developed for sustained delivery of acyclovir to reduce the dosing frequency and improve patient compliance.

Enhanced Transdermal Delivery of Acyclovir via Hydrogel Microneedle Arrays

Hydrogel microneedles represent a promising approach to deliver drug molecules across skin into systemic circulation in a sustained release manner and without any polymer residue within skin. Acyclovir is an antiviral drug used for the treatment of several viral infections. However, the oral administration of acyclovir may cause gastrointestinal tract (GIT) disturbances with low bioavailability and poor patient compliance due to its requirement of five daily administrations to produce the desired effect. Therefore, it is thought that the preparation of hydrogel microneedle arrays containing acyclovir would improve the bioavailability and patient compliance by reducing the frequency of administration to once daily as well as overcome the GIT side effects associated with oral administration. A mixture of PEG 10,000 Da and PMVE/MA co-polymer 1,980,000 Da at a ratio of 1:3 (7.5%:22.5% w/w) with Na2CO3 3% w/w was found to produce the optimum hydrogel microneedle array formulation (F8) which showed suitable needle formation with an appropriate mechanical strength and excellent insertion ability, high drug content, sufficient swelling property and a sustained drug release over a period of 24 hours. The Ex vivo permeation study across human skin has demonstrated that the permeation of acyclovir from F8 hydrogel microneedle array was significantly (P≤ 0.05) increased by 39 times in comparison with microneedle-free film (control). The microneedle array has delivered 75.56% ± 4.2 of its loading dose over 24 hours, while the control film was only able to deliver 1.94% ± 0.14 of the total loading dose during the same period. Accordingly, these findings propose the potential application of hydrogel microneedle arrays for the transdermal delivery of acyclovir in a sustained release manner over 24 hours.

Feasibility of Enhancing Skin Permeability of Acyclovir through Sterile Topical Lyophilized Wafer on Self-Dissolving Microneedle-Treated Skin.

Acyclovir is an antiviral drug that is frequently prescribed for the herpes virus. However, the drug requires frequent dosing due to limited bioavailability (10–26.7%). The rationale of the present study was to develop a self-dissolving microneedle system for local and systemic delivery of acyclovir using a topical lyophilized wafer on microneedle-treated skin to provide the drug at the site of infection. The microneedles prepared with hydroxypropyl methylcellulose (HPMC) (8% w/w) or HPMC (8% w/w)-polyvinyl pyrrolidone (PVP) (30% w/w) penetrated excised rat skin, showing sufficient mechanical strength and rapid polymer dissolution. The topical wafer was prepared with acyclovir (40% w/w; equivalent to 200 mg of drug), gelatin (10% w/w), mannitol (5% w/w), and sodium chloride (5% w/w). The uniform distribution of acyclovir within the wafer in an amorphous form was confirmed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). No polymer–drug interaction was evident in the lyophilized wafer as per Fourier transform infrared spectroscopy (FTIR) analysis. The wafer showed a sufficiently porous structure for rapid hydration as per scanning electron microscopy (SEM) analysis. During ex-vivo analysis, the skin was pre-treated with a self-dissolving microneedle array for 5 minutes, and the wafer was placed on this microporated-skin. Topical wafer provided ∼7–11 times higher skin concentration than the ID99 reported with a lower lag-time. Based on in-vivo testing, ∼2.58 µg/ml of Cmax was achieved in rabbit plasma during 24 hours’ study. Our findings suggest that the self-dissolving microneedle-assisted topical wafer, proposed for the first time, would be efficacious against the infection residing in the skin layer and for systemic therapy.

Nanocrystals for improved topical delivery of medium soluble drug: A case study of acyclovir

Acyclovir is “difficult-to-deliver” topically owing to low lipophilicity and high melting point. The aim of the present study was to develop nanocrystal-based formulations of acyclovir for improved topical delivery. Nanosuspension was optimized with sodium lauryl sulphate and hydroxypropyl cellulose-LF as stabilizers using high speed homogenizer followed by wet media milling. Nanosuspension was characterized by optical microscopy, differential scanning calorimetry, powder-X ray diffraction, dynamic light scattering. Acyclovir nanocrystals were crystalline in nature and exhibited mean particle size of 400–500 nm. Saturation solubility of nanocrystals was improved 1.6-fold over micronized acyclovir. Skin permeation and ex-vivo dermatokinetic studies of cream formulations were performed on pig ear skin at dose of 5% w/w using Franz diffusion cells. Skin permeation studies revealed non-detectable amount of acyclovir in the receptor compartment of Franz diffusion cell. Nanosuspension showed 2- and 2.3-folds drug penetration into the stratum corneum (SC) and viable layers (viable epidermis, dermis), respectively over microsuspension. Nanocream showed 1.6-fold drug penetration into the SC and viable layers over microcream. Further, nanosuspension and nanocream showed statistically significant improvement of 6.3-fold and 2.4-fold in penetration into the viable layers than Zovirax® cold sore cream. Thus, these nano-formulations are useful to improve topical delivery of acyclovir and can help in the treatment of herpes simplex virus infections.

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.

Synthesis, Characterization and Safety Evaluation of Sericin-Based Hydrogels for Controlled Delivery of Acyclovir

Conventional formulations of antiviral drug acyclovir have various limitations such as low bioavailability. The current study was aimed at developing polymeric matrices for the controlled delivery of acyclovir using sericin as polymer and acrylic acid (AA) as a monomer. The free radical polymerization technique was used for hydrogel formulation. Briefly, sericin was chemically cross-linked with acrylic acid. N′-N′-methylene bis-acrylamide (MBA) and ammonium persulfate (APS) were used as cross-linker and initiator, respectively. FTIR spectra showed that acyclovir was successfully loaded into sericin hydrogel. SEM micrographs revealed that the outer surface was solid-like and smooth. According to DSC thermograms, the developed polymeric network was thermally stable. Amorphous nature of acyclovir was observed in XRD. The pH of medium and reactants’ concentration affected swelling dynamics and acyclovir release pattern. In addition, drug release occurred through a diffusion-controlled process. Sericin hydrogel suspension was well tolerable up to 3800 mg/kg of rabbits’ body weight. Haematology and serum chemistry results were well within the range signifying normal liver and kidney functions. Similarly, histopathology slides of the rabbit’s vital organs were also in normal condition without causing any histopathological change. It was concluded from the findings that sericin-co-AA polymeric matrices are ideal for the pH-dependent delivery of acyclovir.

Poloxamer Modified Chitosan Nanoparticles for Vaginal Delivery of Acyclovir.

The aim of the present study was to design a surface modified chitosan nanoparticle system for vaginal delivery of acyclovir for effective drug uptake into vaginal mucosa. Acyclovir-loaded chitosan nanoparticles, with and without modification by poloxamer 407, were prepared by ionic gelation method. The effects of two independent variables, chitosan to sodium tripolyphosphate mass ratio (X1) and acyclovir concentration (X2), on drug entrapment in nanoparticles were studied using 32 full factorial design. The surface response and counterplots were drawn to facilitate an understanding of the contribution of the variables and their interaction. The nanoparticles were evaluated for drug entrapment, size with zeta potential, morphological analysis by TEM, solid-state characterization by FTIR, DSC, XRD, in vitro dissolution, in vitro cell uptake using HeLa cell line and in vivo vaginal irritation test in Wistar rats. Chitosan nanoparticle formulation with chitosan to sodium tripolyphosphate mass ratio of 2:1 and acyclovir concentration of 2 mg/mL resulted in the highest entrapment efficiency. The resulting nanoparticles revealed spherical morphology with a particle size of 191.2 nm. The surface modification of nanoparticles with poloxamer resulted in higher drug entrapment (74.3±1.5%), higher particle size (391.1 nm) as a result of dense surface coating, lower zeta potential and sustained drug release compared to unmodified nanoparticles. The change in the crystallinity of the drug during nanoparticle formulation was observed in DSC and XRD study. Cellular uptake of poloxamer-modified chitosan nanoparticles was found to be higher than chitosan nanoparticles in HeLa cells. Safety of nanoparticle formulations by vaginal route was evident when tested in female rats. Conclusively, poloxamer-modified CH NP could serve as a promising and safe delivery system with enhanced cellular drug uptake.

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.

MUCOADHESIVE POLYMERIC FILMS OF ACYCLOVIR PRONIOSOMES FOR BUCCAL ADMINISTRATION

Objective: The aim of the present work was to formulate and evaluate proniosomes of the poorly soluble drug, acyclovir incorporated in mucoadhesive polymeric films for improved buccal mucosal permeability of the drug while achieving prolonged release.&#x0D; Methods: Acyclovir was formulated as proniosomes using Span 60 and cholesterol. The prepared proniosomes were loaded into mucoadhesive polymeric films prepared with varying quantities of carbopol 934P and HPMC K15M. The proniosome incorporated films were evaluated for physicomechanical characters, mucoadhesion, swelling index, drug content, in vitro drug release and ex vivo permeation through porcine buccal mucosa.&#x0D; Results: Hydration of the proniosomes produced spherical vesicles or niosomes, which was confirmed by Scanning Electron Microscopy. The optimized formulation selected on the basis of vesicle size, entrapment efficiency PDI, Zetz potential and in vitro drug release was selected for incorporation into mucoadhesive polymeric films. All the films showed excellent physicomechanical characters. Formulations with higher proportions of carbopol produced slower in vitro drug release. The kinetics of release of drug from all the formulations appeared to be zero-order based on their regression coefficient values. Comparative evaluation of ex vivo permeation from niosomal and non-niosomal films indicated that the former demonstrated improved mucosal permeation and drug release was also sustained for the 8 h period.&#x0D; Conclusion: Mucoadhesive films impregnated with acyclovir loaded proniosomes could be a potential approach for buccal delivery of acyclovir for improving its absorption and bioavailability.

Synthesis and Application of ZIF‐8 MOF Incorporated in a TiO2@Chitosan Nanocomposite as a Strong Nanocarrier for the Drug Delivery of Acyclovir

AbstractRecently, metal‐organic frameworks (MOFs) have been effectively established as potential nanocarriers for the drug delivery. In this study, we have examined a novel framework containing TiO2@Chitosan@ZIF‐8 for the delivery of acyclovir (ACV). The structure elucidation and physicochemical characterization of the prepared nanocarrier were investigated by various spectroscopic techniques such as Fourier‐transform infrared spectroscopy (FT‐IR), ultraviolet‐visible spectroscopy (UV‐Vis), energy‐dispersive X‐ray spectroscopy (EDX), X‐ray diffraction (XRD), field emission scanning electron microscopy (FE‐SEM), brunauer‐emmett‐teller (BET), and thermal gravimetric analysis (TGA). The obtained results demonstrated that 90 % of the acyclovir was loaded on the TiO2@Chitosan@ZIF‐8 framework. The drug release study was performed in PBS (phosphate buffer saline, pH:7.4) and AB (acetate buffer, pH:5) solutions, which showed 78 % and 82 % release within 3 days.

Formulation and Evaluation of Microemulsion Based in Situ Gel of Acyclovir for Vaginal Delivery

The purpose of the present study was to formulate and evaluate microemulsion based in situ gel of Acyclovir (ACV) for the vaginal delivery. The solubility of ACV in oils and surfactants and co-surfactant was evaluated to identify the components of the microemulsion. Microemulsion region was determined by using the pseudo-ternary phase diagrams for different formulations. Microemulsion formulation was prepared using Labrafil M1994C as oil phase, Cremophor RH40 as surfactant and Polyethylene glycol 400 and Transcutol P as co-surfactant and water. Microemulsion formulations were evaluated for pH, viscosity, conductivity and stability study. In situ gel of ACV, microemulsion was prepared using thermosensitive polymer, poloxamer.In situ gelwas characterized for viscosity, gelling temperature, the effect of dilution on gelling temperature, gelling ability, and in vitro drug release and release kinetics. The globule size of developed microemulsion was less than 100 nm with PDI in the range 0.307 to 0.641. The optimized microemulsion based in situ gel demonstrated shear thinning behaviour, the gelation temperature with and without dilution was in the range of 30-35ºC, and the drug release was sustained over eight hours. Mucoadhesive properties of microemulsion based in situ gel formulations were determined with a texture analyzer using a goat vaginal tissue, and the results indicated that the presence of microemulsion increased the mucoadhesion significantly. Microemulsion based in situ gel was successfully developed for vaginal delivery of Acyclovir.

Development of Dose Sipping Technology, a New Design Approach for Improving Drug Delivery of Acyclovir in Pediatric Medication

Development of Dose Sipping Technology, a New Design Approach for Improving Drug Delivery of Acyclovir in Pediatric Medication

N,N,N-trimethylchitosan-poly (n-butylcyanoacrylate) core-shell nanoparticles as a potential oral delivery system for acyclovir

This study investigated the feasibility of polysaccharide-coated poly(n-butyl cyanoacrylate) (PBCA) nanoparticles for oral delivery of acyclovir (ACV). PBCA nanoparticles were obtained by the emulsion polymerization method. Chitosan was chemically modified to obtain N,N,N-trimethylchitosan (TMC), which was used to coat the nanoparticles (PBCA-TMC). Nanoparticles were characterized by dynamic light scattering, zeta potential, differential scanning calorimetry (DSC), atomic force microscopy (AFM), cytotoxicity, and the effect on the transepithelial electrical resistance (TEER) of the Caco-2 cells. The size of the coated nanoparticles (296.2 nm) was significantly larger than uncoated (175.0 nm). Furthermore, PBCA nanoparticles had a negative charge (-11.7 mV), which was inverted to highly positive values (+36.5 mV) after coating. DSC analysis suggested the occurrence of the coating, which was confirmed by AFM images. The MTT assay revealed concentration-dependent cytotoxicity for the core-shell nanoparticles. Additionally, PBCA-TMC caused a significant but reversible decrease in the Caco-2 cell monolayer TEER. Entrapped ACV (PBCA-ACV-TMC), a Biopharmaceutical Classification System class III drug substance, increased approximately 3.25 times the Papp of ACV in the Caco-2 permeability assay. The nanoparticles were also able to provide in vitro ACV controlled release using media with different pH values (1.2; 6.8; 7.4). Accordingly, this new core-shell nanoparticle showed the potential to improve the oral delivery of ACV.

Fabrication of temperature and pH sensitive decorated magnetic nanoparticles as effective biosensors for targeted delivery of acyclovir anti-cancer drug

Magnetic nanoparticles are promising materials for a variety of applications, especially in the delivery and controlled release of various drugs. These compounds present a major obstacle to the treatment of many diseases and have a pivotal role in the future of personalized medicine. In the present study, adsorption and delivery of acyclovir (ACV) on pristine and modified magnetic nanoparticles are investigated. The as-synthesized magnetite nanoparticles are decorated with 3-(triethoxysilyl)-propylamine prior loading of ACV and samples are characterized by means of SEM, TEM, VSM, DLS, and zetametry studies. VSM and zeta potential studies show that ACV decreases the saturation magnetization and zeta potential of magnetite nanoparticles. Then, adsorption of ACV in phosphate buffered saline was examined and effects of some variables including pH, loading time and temperature are briefly investigated. Our experimental results revealed the best loading (~80%) can be achieved at pH 9 at 39 °C after 5 h. The loading efficacy may be assigned to the increment of hydrogenic interactions under the loading process. Eventually, a DFT study was fully investigated to provide important theoretical parameters related to the adsorption process. The performed computations on pristine and doped Fe3O4 nanoparticles prove strong interactions between nitrogen and oxygen atoms of acyclovir with Fe+3 ions of magnetic nanoparticles. Moreover, additional hydrogen bonds between active sites of the adsorbed drug molecule and Fe3O4 fragments lead to a significant adsorption and stabilization of the obtained configurations. The nature of intermolecular interactions, electron densities, and Laplacians is also fully investigated at the bond critical points. Natural bond orbital analysis confirms that acyclovir can be adsorbed on the surface of Fe3O4 nanoparticle with a charge transfer from acyclovir to the nanoparticle. In addition, the modified and doped Fe3O4 nanoparticles can absorb drug molecules more strongly compared to the pristine counterpart and generate stable configurations. Interestingly, doping with Zn atom results in an electronic hole, hence, the conductivity of the Fe3O4 may be enhanced. Therefore, Zn impurities can introduce local states inside the Eg and improve reactivity of magnetic nanostructures towards adsorption process. Therefore, the examined metal-doped magnetic nanoparticles in this study can be applied as promising nanobiosensors for detection and delivery of ACV in medicine.