Development of a PVA/PCL/CS-Based Nanofibrous Membrane for Guided Tissue Regeneration and Controlled Delivery of Doxycycline Hydrochloride in Management of Periodontitis: In Vivo Evaluation in Rats.

Antibiotic administration is an adjacent therapy to guided tissue regeneration (GTR) in the management of periodontitis. This is due to the major role of pathogen biofilm in aggravating periodontal defects. This study aimed to fabricate a GTR membrane for sustained delivery of doxycycline hydrochloride (DOX) while having a space-maintaining function. The membranes were prepared using a polymeric blend of polycaprolactone/polyvinyl alcohol/chitosan by the electrospinning technique. The obtained membranes were characterized in terms of physicochemical and biological properties. Nanofibers showed a mean diameter in the submicron range of < 450 nm while having uniform randomly aligned morphology. The obtained membranes showed high strength and flexibility. A prolonged in vitro release profile during 68 h was observed for manufactured formulations. The prepared membranes showed a cell viability of > 70% at different DOX concentrations. The formulations possessed antimicrobial efficacy against common pathogens responsible for periodontitis. In vivo evaluation also showed prolonged release of DOX for 14 days. The histopathological evaluation confirmed the biocompatibility of the GTR membrane. In conclusion, the developed nanofibrous DOX-loaded GTR membranes may have beneficial characteristics in favour of both sustained antibiotic delivery and periodontal regeneration by space-maintaining function without causing any irritation and tissue damage.

Exercise training reduces systemic inflammation and improves general health status in female migraineurs: a randomised controlled trail.

OBJECTIVES: The objectives of this study were to assess the effect of 8 weeks of moderate-intensity aerobic training on permeability inflammatory indicators of matrix metalloproteinases (MMPs) and specific tissue inhibitors of MMPs in female migraineurs. METHODS: Female migraineurs (n = 28, age 32 ± 6) were randomised into two groups: migraine with exercise training (EXE + Mig, n = 13) and migraine without exercise training (NON-EXE + Mig, n = 15). Matched healthy women were also recruited as a healthy control group (CON, n = 15). The EXE-Mig group performed 8 weeks of aerobic training. Pre and post intervention, serum matrix metalloproteinases (MMP-2 and 9) and specific tissue inhibitors of MMPs (TIMP-1 and 2) were measured. In addition, body composition indices and VO2max were determined. RESULTS: Exercise training reduced serum MMP-9 in female migraineurs with between-group changes and a time x group interaction (p < 0.05). In addition, exercise training reduced the serum MMP-9/TIMP-1 ratio in female migraineurs with between-group changes and time x group interaction (p < 0.05). However, no training-induced effect was observed in serum TIMP-1, TIMP-2, MMP-2 contents (p > 0.05) and MMP-2/TIMP-2 ratio (p > 0.05). Finally, exercise training reduced body fat content, WHR and BMI, and improved VO2max (p < 0.01). CONCLUSIONS: Our results demonstrated beneficial effects of aerobic exercise training on some circulatory inflammation factors (MMP9, MMP-9/TIMP-1) and some health indicators in female migraineurs, suggesting that such training can be employed as a non-pharmacological therapeutic method.

Preparation and functional evaluation of electrospun polymeric nanofibers as a new system for sustained topical ocular delivery of itraconazole.

Due to the rapid clearance of external agents from the surface of the cornea, conventional ocular formulations usually require frequent and long duration of administration to achieve a therapeutic level of the drug on the cornea which can be conquered using prolonged-release nanofibrous inserts. In the present study, for the first time, polymeric nanofibers of itraconazole (ITZ), a potent triazole antifungal agent, were prepared as ocular inserts to enhance the topical ocular delivery of the drug. Three different nanofibers were prepared by electrospinning using polyvinyl alcohol-cellulose acetate and polycaprolactone-polyethylene glycol 12 000 polymeric blends. Nanofibers indicated uniform structures with the mean diameter ranging between 137 and 180 nm. Differential scanning calorimetry and Fourier-transform infrared spectroscopy confirmed the amorphous state of the drug in the formulations and the no drug-polymer interaction. Appropriate stability, suitable flexibility, and 2.2-3.9 MPa tensile strength were observed. Formulations indicated antifungal efficacy against Candida albicans and Aspergillus fumigatus and cell viability >70% at different concentrations. Results of bioassay against Candida albicans exhibited prolonged in vitro release of 50-70% of ITZ for almost 55 days. The results suggested that the nanofibers could be considered suitable for prolonged delivery of the ITZ as an antifungal requiring frequent and long duration of administration.

Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation.

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

Preparation of polycaprolactone and polymethacrylate nanofibers for controlled ocular delivery of ketorolac tromethamine: Pharmacokinetic study in Rabbit's Eye.

Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 µg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC0-144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.

Design and development of dual drug-loaded nanofibrous inserts for ophthalmic sustained delivery of AMK and VAN: Pharmacokinetic study in rabbit's eye.

Bacterial corneal keratitis is a damage to the corneal tissue that if not treated, can cause various complications like severe vision loss or even blindness. Combination therapy with two antibiotics which are effective against Gram-positive and Gram-negative bacteria offers sufficient broad-spectrum antibiotic coverage for the treatment of keratitis. Nanofibers can be a potential carrier in dual drug delivery due to their structural characteristics, specific surface area and high porosity. In order to achieve a sustained delivery of amikacin (AMK) and vancomycin (VAN), the current study designed, assessed, and compared nanofibrous inserts utilizing polyvinyl alcohol (PVA) and polycaprolactone (PCL) as biocompatible polymers. Electrospinning method was utilized to prepare two different formulations, PVA-VAN/AMK and PCL/PVA-VAN/AMK, with 351.8 ± 53.59 nm and 383.85 ± 49 nm diameters, respectively. The nanofibers were simply inserted in the cul-de-sac as a noninvasive approach for in vivo studies. The data obtained from the physicochemical and mechanical properties studies confirmed the suitability of the formulations. Antimicrobial investigations showed the antibacterial properties of synthesized nanofibers against Staphylococcus aureus and Pseudomonas aeruginosa. Both in vitro and animal studies demonstrated sustained drug release of the prepared nanofibers for 120 h. Based on the in vivo findings, the prepared nanofibers' AUC0-120 was found to be 20 to 31 times greater than the VAN and AMK solutions. Considering the results, the nanofibrous inserts can be utilized as an effective and safe system in drug delivery.

Development of fexofenadine self-microemulsifying delivery systems: an efficient way to improve intestinal permeability.

Aim: The present study aimed to prepare and evaluate fexofenadine self-microemulsifying drug-delivery systems (SMEDDS) formulation and to determine and compare its intestinal permeability using in situ single-pass intestinal perfusion (SPIP) technique.Methods: Fexofenadine-loaded SMEDDS were prepared and optimized. Droplet size, polydispersity index, zeta potential, drug release and intestinal permeability were evaluated.Results: Optimized formulation consisted of 15% oil, 80% surfactant and 5% cosolvent. Droplet size and drug loading of optimized formulation was 13.77 nm and 60 mg/g and it has released 90% of its drug content. Intestinal permeability of fexofenadine was threefold enhanced in SMEDDS compared with free fexofenadine.Conclusion: The results of our study revealed that SMEDDS could be a promising tool for oral delivery of fexofenadine with enhanced dissolution rate and intestinal permeability.

[Box: see text].

Macrolide-loaded nanofibrous inserts with polycaprolactone and cellulose acetate base for sustained ocular delivery: Pharmacokinetic study in Rabbit's eye.

The present study aimed to prepare nanofibrous inserts for sustained ocular drug delivery of Azithromycin (AZM) toward conquering the obstacles of conventional topical drug delivery. Nanofibers were fabricated by electrospinning using polycaprolactone (PCL) and cellulose acetate (CA) which are biocompatible and biodegradable polymers. Prepared nanofibers were evaluated in terms of physicochemical, morphological properties, pharmacokinetic study and ocular irritation. SEM images revealed average diameters of about 160 nm and 190 nm for CA and PCL nanofibers, respectively. These ocular drug delivery systems were strong, flexible, and stable under humid and dry conditions. Quantification was performed using microbiological assay by M. luteus as a microorganism. While PCL-based nanofibrous inserts released AZM in a two-step manner initiated by a burst release via Peppas kinetical model, CA-based inserts showed a gradual release profile without any burst release which followed the first-order model. Results showed that these inserts were non-cytotoxic and non-irritating. The nanofibers showed antibacterial efficacy against Escherichia coli and Staphylococcus aureus. In addition, according to a pharmacokinetic study in Rabbit's Eye, a higher Cmax and lower Tmax were achieved by PCL nanofibers compared to CA-based ones. The pharmacokinetic study of nanofibers in rabbit eyes showed that all formulations were able to maintain the effective concentration of AZM for about 6 days. In conclusion, the prepared nanofibers can be effectively utilized for prolonged ocular delivery of AZM in the treatment of conjunctival infections.

Fabrication of Anti-glaucoma Nanofibers as Controlled-Release Inserts for Ophthalmic Delivery of Brimonidine Tartrate: In Vivo Evaluation in Caprine Eye.

Purpose: Chronic ailments usually decrease the quality of life due to the requirement for repetitive administration of drugs. Glaucoma is a chronic eye disease occurred because of increased intraocular pressure (IOP). Controlled-release inserts can overcome this challenge by a gradual release of the antiglaucoma drugs. This study aimed to fabricate ocular inserts of brimonidine tartrate (BMD) for the management of glaucoma. Methods: Different polymers including poly (D, L-lactide), polycaprolactone, cellulose acetate, and Eudragit RL100® were used to develop the BMD-loaded nanofibrous inserts by electrospinning technique. The inserts were characterized. The morphology and drug-polymer compatibility were examined by scanning electron microscopy (SEM), and Fourier-transform infrared (FTIR) spectroscopy and in vitro drug release in PBS. The IOP-lowering efficacy and irritancy of optimized formulation were assessed in the caprines. Results: SEM images demonstrated nanofibers with uniform morphology and a mean diameter<300 nm were fabricated. The nanofibers were high-strength and flexible enough to be placed in the conjunctival sac. FTIR showed drug-polymer compatibility. In vitro release study indicated a sustained-release profile of the drug during 6 days for inserts. In vivo evaluation indicated that the optimized formulation is capable of maintaining the IOP in a non-glaucomatous range for an extended duration of 6 days. In addition, the formulation was non-irritant to the caprine eye. Conclusion: Due to the prolonged IOP-lowering efficiency, BMD-loaded nanofibrous inserts can be considered suitable for the controlled release of drugs and thus enhance patient compliance by reducing the frequency of administration.

Optimization of a Self-microemulsifying Drug Delivery System for Oral Administration of the Lipophilic Drug, Resveratrol: Enhanced Intestinal Permeability in Rat.

Purpose: This study aimed to formulate Resveratrol, a practically water-insoluble antioxidant in a self-microemulsifying drug delivery system (SMEDDS) to improve the solubility, release rate, and intestinal permeability of the drug. Methods: The suitable oil, surfactant, and co-surfactant were chosen according to the drug solubility study. Utilizing the design of experiment (DoE) method, the pseudo-ternary phase diagram was plotted based on the droplet size. In vitro dissolution study and the single-pass intestinal perfusion were performed for the investigation of in vitro and in-situ permeability for drugs formulated as SMEDDS in rat intestine using High-Performance Liquid Chromatography. Results: Castor oil, Cremophor® RH60, and PEG 1500 were selected as oil, surfactant, and co-surfactant. According to the pseudo-ternary phase diagram, nine formulations developed microemulsions with sizes ranging between 145-967 nm. Formulations passed the centrifuge and freeze-thaw stability tests. The optimum formulation possessed an almost 2.5-fold higher cumulative percentage of in vitro released resveratrol, in comparison to resveratrol aqueous suspension within 120 minutes. The results of the in-situ permeability study suggested a 2.6-fold higher intestinal permeability for optimum formulation than that of the resveratrol suspension. Conclusion: SMEDDS can be considered suitable for the oral delivery of resveratrol according to the observed increased intestinal permeability, which could consequently enhance the bioavailability and therapeutic efficacy of the drug.

Preparation and Evaluation of Nanofibrous and Film-Structured Ciprofloxacin Hydrochloride Inserts for Sustained Ocular Delivery: Pharmacokinetic Study in Rabbit's Eye.

Conventional anti-infective eye drops are the most common forms of drugs prescribed for the management of topical ocular infections. Despite their convenience, topical eye drops face multiple challenges, including limited bioavailability and repetitive administration. The present study aimed to prepare, evaluate, and compare film-structured and nanofibrous ocular inserts using biocompatible polymers of polyvinyl alcohol (PVA) and polycaprolactone (PCL) to achieve sustained ciprofloxacin Hydrochloride (CIP) delivery. The nanofibrous formulations were prepared by electrospinning and glutaraldehyde crosslinking while the film formulation was prepared by solvent casting. Nanofibrous inserts had mean diameters in the range 330-450 nm. Both film and nanofibrous inserts were strong, although the nanofibers had higher flexibility. In vitro antibacterial efficacy against Staphylococcus aureus and Escherichia coli was observed for all formulations and cell viability of more than 70% confirmed their non-toxicity. In vitro release studies showed prolonged release of 2 days for the film and 5 days for the nanofibers compared with a 10-h release of CIP from the eye drop. Pharmacokinetic studies of rabbits' eyes showed 4.5-5-folds higher AUC for the nanofiber formulations compared with the eye drop. Thus, prolonged-release film-structured and nanofibrous inserts are suitable carriers for ocular delivery of CIP.

Preparation and characterization of alginate and psyllium beads containing Lactobacillus acidophilus.

This paper describes preparation and characterization of beads of alginate and psyllium containing probiotic bacteria of Lactobacillus acidophilus DMSZ20079. Twelve different formulations containing alginate (ALG) and alginate-psyllium (ALG-PSL) were prepared using extrusion technique. The prepared beads were characterized in terms of size, morphology and surface properties, encapsulation efficiency, viabilities in acid (pH 1.8, 2 hours) and bile (0.5% w/v, 2 hours) conditions, and release in simulated colon pH conditions. The results showed that spherical beads with narrow size distribution ranging from 1.59 ± 0.04 to 1.67 ± 0.09 mm for ALG and from 1.61 ± 0.06 to 1.80 ± 0.07 mm for ALG-PSL with encapsulation efficiency higher than 98% were achieved. Furthermore, addition of PSL into ALG enhanced the integrity of prepared beads in comparison with ALG formulations. The results indicated that incorporation of PSL into alginate beads improved viability of the bacteria in acidic conditions as well as bile conditions. Also, stimulating effect of PSL on the probiotic bacteria was observed through 20-hour incubation in simulated colonic pH solution. According to our in vitro studies, PSL can be a suitable polymer candidate for partial substitution with ALG for probiotic coating.

Design of Novel Nanoemulsion Formulations for Topical Ocular Delivery of Itraconazole: Development, Characterization and In Vitro Bioassay.

Purpose: The objective of this study was to design and develop nanoemulsion formulations of Itraconazole (ITZ), a water-insoluble, potent antifungal drug using the spontaneous emulsification method, to improve the ocular delivery and achieve a sustained release of the drug. Methods: The oil was selected on the basis of the ITZ solubility while the surfactant and co-surfactant were selected based on the thermodynamic stability and globule size. Following the selection of components, a pseudo-ternary phase diagram was constructed for the most promising formulation (F11) using benzyl benzoate (BB) as the oil, Eumulgin CO40 as the surfactant, and propylene glycol as the co-surfactant, by the design of experiments (DoE). Results: F7 and F11 formulations were found to have an average globule size of 223.5 ± 10.7 nm and 157.5 ± 14.2 nm, besides thermodynamic stability and suitable physicochemical properties. F11 possessed an almost seven-fold higher cumulative percentage of in vitro released ITZ, in comparison to ITZ aqueous suspension after 24 hours. The release data suggested that the best fitted kinetical model for F11 and F7 was the Higuchi and Korsmeyer-Peppas model. Conclusion: The extended-release of the drug beside an acceptable amount of loaded ITZ suggested that nanoemulsion is suitable for the delivery of the ITZ.

Design and Development of Antibacterial/Anti-inflammatory Dual Drug-Loaded Nanofibrous Inserts for Ophthalmic Sustained Delivery of Gentamicin and Methylprednisolone: In Vitro Bioassay, Solvent, and Method Effects' Evaluation.

Purpose: To overcome the challenges caused by the use of conventional ophthalmic dosage forms such as the fast elimination of the drug from the surface of the eye, in this study, dual drug-loaded nanofibers were developed for sustained ophthalmic delivery of gentamicin (GNT) and methylprednisolone (MP). Moreover, the solvent effects, polymer mixtures, and method of preparation on the release profile of the prepared nanofibers, were evaluated. Methods: The nanofibers were prepared using polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and polyvinyl alcohol (PVA) using electrospinning technique. Thereafter, seven optimized formulations were developed with different solvent mixtures and polymer concentrations using various electrospinning methods. The physicochemical and mechanical properties of nanofibers were also evaluated, and the morphology of formulations was observed. The antibacterial efficacy was investigated and the in vitro release amounts of GNT and MP from nanofibers were estimated using the bioassay and ultraviolet-visible (UV-Vis) spectroscopy. Results: The developed G1, G4, G5, G6, and G7 had suitable mechanical properties and morphologies with diameter ranging between 70-350 nm. The 1:1 v/v ratio of DMF/DCM in the solvent mixture and using core-shell technique for the preparation, formed nanofibers with more favorable release profiles. The optimized formulations indicated sustained-release manner for both drugs during 3-9 days and the antibacterial efficacy against Staphylococcus aureus. Conclusion: Among all the prepared formulations, the nanofiber with core-shell structure possessed the best sustained-release profiles of GNT and MP. The obtained results suggest that these nanofibers have a potential to be used as an insert in the eye for long-term release of the drug.

Preparation of Azithromycin Nanofibers as Controlled Release Ophthalmic Drug Carriers Using Electrospinning Technique: In Vitro and In Vivo Characterization.

Purpose: Conventional topical dosage forms face with some challenges like low intraocularbioavailability, which could be overcome by application of novel drug delivery systems.Therefore, this study was conducted to prepare azithromycin (AZM)-loaded chitosan/polyvinylalcohol/polyvinyl pyrrolidone (CS/PVA-PVP) nanofibers with the prolonged antibacterialactivity by electrospinning method. Methods: After preparation of nanofibers, they were characterized in terms of physicochemicaland morphological properties. In vitro and in vivo release of the drug from nanofibers wereevaluated using microbial assay against the Micrococcus luteus. Antibacterial efficacy of thenanofibers was assessed. The ophthalmic irritation test was also performed. MTT test wascarried out to evaluate cytotoxicity of the formulations. Results: All the formulations were found to be stable with uniform thickness, weight, and drugcontent. Nanofibers had a diameter range from 119 ± 29 to 171 ± 39 nm. The inserts were nonirritantand non-toxic to the rabbits' eye. Based on the obtained results, the crosslinked AZMnanofibers showed slower and more controlled drug release in tear fluid compared to the noncrosslinkedones, within 184 hours. Conclusion: Our results revealed that the prepared nanofibers could be considered as suitableand non-invasive inserts for the prolonged ophthalmic delivery of AZM.

Eudragit® L100/Polyvinyl Alcohol Nanoparticles Impregnated Mucoadhesive Films as Ocular Inserts for Controlled Delivery of Erythromycin: Development, Characterization and In Vivo Evaluation.

The fast elimination of drugs from the cornea is one of many challenges associated with the topical administration of conventional dosage forms. The present manuscript aimed to prepare modified-release inserts containing erythromycin (ERY) to enhance drug delivery and address the aforementioned limitation. Film formulations were developed using Eudragit® L100 (EUD) and Polyvinyl Alcohol (PVA) polymers. ERY-loaded EUD-based nanoparticles were developed by the colloidal dispersion method using PVA as the emulsifier. The film-casting method was applied to form the mucoadhesive films using sodium alginate, gelatin, cyclodextrin-α, and ß as polymeric film matrices. Different physicochemical properties of the optimized formulations and in vitro release profiles were evaluated. The in vivo evaluation was performed by collecting tear samples of rabbits using a novel, non-invasive method following the administration of inserts in the cul-de-sac. The ERY amount was assayed using a microbiological assay. The developed films showed prolonged in vitro and in vivo release profiles over five to six days; they had suitable physicochemical properties and a tensile strength of 2-3 MPa. All formulations exhibited antibacterial efficacy against E. coli and S. aureus with more than 20 mm diameter of inhibited growth zones. None of the formulations caused irritation to the rabbit's eye. The inserts showed promising pharmacokinetics with AUC0-120 of 30,000-36,000 µg·h/mL, a Cmax of more than 1800 µg/mL at 4 h, and maintained drug concentration over the threshold of 5 µg/mL during the following 120 h of study. Nanoparticle-containing, mucoadhesive films could be fabricated as ocular inserts and can prolong the topical ocular delivery of ERY.

A novel drug delivery system using acyclovir nanofiber patch for topical treatment of recurrent herpes labialis: A randomized clinical trial.

OBJECTIVES: Topical treatment with acyclovir cream has shown low efficacy in recent studies. Nano drug delivery systems, have received much attention in recent decades. The aim of this study was to compare the efficacy of acyclovir nanofiber patch with acyclovir cream. MATERIAL AND METHODS: In this double-blind three-armed randomized clinical trial, a total of 60 patients with recurrent labial herpes, were randomly divided into three groups, each consisting of 20. The patients in the first, second, and third groups were treated with acyclovir nanofiber patch, placebo nanofiber patch, and acyclovir cream, respectively. A numerical scale was used by the patients to record the self-reported symptoms. Symptoms score, crusting time and healing time were assessed by the clinician. Kruskal-Wallis test was used to compare the symptoms between the three groups, a survival test was also performed to evaluate the crusting and healing time. Data were analyzed in SPSS V22 at P-value < 0.05. RESULTS: The mean scores of symptoms at baseline were 1.6, 1.5, and 1.4 in the first, second, and third groups, respectively. The symptoms were not significantly different between the three groups on different treatment days. The mean crusting time was 2.3, 2.4, and 2.6 days in the three groups, and the mean healing time was 7.4, 7.2, and 7.7 days, respectively. Crusting time and healing time were not significantly different between the three groups. CONCLUSIONS: Acyclovir nanofiber patches are recommended for accelerating symptom relief in recurrent labial herpes, however, they are not effective in shortening the crusting or healing time. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20141124020073N2. Registered in: Iranian Registry of Clinical Trials (www.irct.ir).

Development and evaluation of polycaprolactone-based electrospun nanofibers containing timolol maleate as a sustained-release device for treatment of glaucoma: in vivo evaluation in equine eye.

Background and purpose: Prolonging the drug release can be a suitable approach to overcome the challenges related to topical ophthalmic administration of drugs especially the ones prescribed for chronic ailments. The sustained delivery of the drug would reduce the required frequency of administration which could extremely improve patient compliance and feeling of well-being. This study aimed to develop nanofibrous inserts for sustained ophthalmic delivery of timolol maleate (TIM) for the treatment of glaucoma. Experimental approach: Polycaprolactone-based nanofibers containing TIM were prepared using pure polycaprolactone or a blend of it with cellulose acetate or Eudragit RL100 polymers by the electrospinning method. Following the preparation, polymeric inserts were evaluated for morphological and physicochemical properties. The in vitro drug release was assessed and the in vivo efficacy of a selected insert in decreasing the intraocular pressure (IOP) was also evaluated in the equine eyes. Findings / Results: Prepared nanofibers indicated diameter ranged between 122-174 nm. The formulations showed suitable physicochemical properties and stability for ophthalmic administration. In vitro release study showed prolonged release of drug during more than 3 days. In vivo evaluation revealed that the prepared insert is non-irritant and non-toxic to the equine eyes while having suitable efficacy in decreasing the IOP during 6 days. Conclusions and implication: Prepared TIM inserts indicated a higher efficacy than commercial TIM eye drop in lowering IOP during a prolonged period. Thus, these formulations can be considered suitable for enhancing patient compliance by reducing the frequency of administration in the treatment of glaucoma.

The formulation and efficacy of topical Dorema ammoniacum in treating Melasma: a randomized double-blind, placebo-controlled trial.

OBJECTIVES: An acquired melanin-related hyperpigmentation that occurs in sun exposure areas is Melasma which presents as gray-brown ridges and macules with prominent margins on the skin. The aim of this assay was to assess the formulation and efficacy of topical Dorema ammoniacum among Melasma patients. METHODS: This study was a 30 days double-blind, randomized clinical trial in Melasma with a placebo group. The study was carried out on 49 patients with Melasma attending Haji Daii Nursing Center in Kermanshah, Iran. Optimized topical formulation of D. ammoniacum gum extract was prepared by evaluating the characteristics of different topical formulations of this plant. Mean Melasma severity index (MMASI) instrument was applied to assess the product effectiveness and to determine the skin stains. Patients were pursued to receive the treatment throughout the 30 days trial. This scaling was accomplished before the intervention and 30 days after the use of the herbal product. To analyze the quantitative variables, t-test and Mann-Whitney test were evaluated by SPSS 21 software, and p-value <0.05 was considered as the statistically significant. RESULTS: The survey was performed on 40 female subjects (81.6%) and nine male subjects (18.4%) with the mean age of 32.18 ± 8.69. According to the results, the mean MSI in the drug group was significantly lower than before treatment and decreased from 86.98 ± 69.48 to 31.03 ± 32.62 (p-value <0.05). CONCLUSIONS: In compliance with findings this survey revealed a positive effect of the cream formulation of D. ammoniacum extract on Melasma. As it was represented no side effects, this formulation is appropriate for the treatment of Melasma.