Effect of herbal cream containing Fumaria officinalis and silymarin for treatment of eczema: A randomized double-blind controlled clinical trial.

Objective: Atopic dermatitis (AD) is a common skin disorder with symptoms including severe pruritus and eczematous lesions. AD affects between 5 and 20% of people in their life. Silymarin (SM) is a polyphenolic flavonoid from Silybum marianum L. and has several therapeutic characteristics including antiallergic, anticancer, and anti-inflammatory properties. Fumaria officinalis is a small plant that has a high antioxidant power and modulating effects on the immune system. Therefore, the current study intended to examine the influence of these two herbs extract on severity and symptoms of AD in patients. Materials and Methods: 40 patients with mild to moderate eczema randomly received mometasone 0.1% or the herbal cream. Treatment course was 2 weeks and patients were examined before and after 2 weeks of treatment using the SCORAD system. Results: The reduction of SCORAD score was significant in both groups (p=0.04 in the herbal group and p=0.03 in the mometasone group) but no significant difference was observed between the groups. Mean SCORAD score was 27.66±5.9 before therapy and 4.77±1.6 after therapy in the mometasone group and mean SCORAD score was 26.05±7.1 before therapy and 6.944±2.6 after therapy in the herbal group. Conclusion: The current study indicated the impact of these two herbs extract on severity and symptoms of AD in patients; these plants may be a new treatment in reducing eczema symptoms and its problems.

Dermal pharmacokinetics of rivastigmine-loaded liposomes: an ex vivo-in vivo correlation study.

The aim of the present study was to develop a topical liposomal formulation as a transdermal delivery of rivastigmine for the treatment of Alzheimer's disease as an alternative to the oral dosage form and to achieve smooth continuous drug delivery and maintain plasma levels within the therapeutic window. Rivastigmine-loaded liposomes were prepared by a thin layer hydration technique that was applied in ex vivo-in vivo correlation study. Permeability parameters through rat skin in ex vivo study and pharmacokinetic parameters in the in vivo study were evaluated. The ex vivo permeation study showed that liposomes provided steady-state flux 0.11 ± 0.01 mg/cm.h that were more than 2-fold the aqueous control. In the in vivo experiments, after topical application of optimized rivastigmine liposomes, the Cmax 208 ng/ml and AUC0-24 3605 (ng.h/ml) were also significantly higher than the control group (both p < 0.01). A point-to-point significant linear correlation was found between ex vivo and in vivo parameters, meaning in vivo pharmacokinetic parameters can be predicted by ex vivo permeation parameters. These data suggest that a liposomal formulation could be an effective carrier to enhance rivastigmine permeation through the skin and maintain plasma levels within the therapeutic window.

Preparation and optimization of silibinin-loaded chitosan-fucoidan hydrogel: an in vivo evaluation of skin protection against UVB.

PURPOSE: The objective of this study was to develop silibinin-loaded hydrogel for skin protection against UVB damage. METHOD: Physical grafting was used to prepare hydrogel based on chitosan-fucoidan. Then, hydrogel properties, such as swelling, drug release rates, morphology, and structure, were evaluated to determine the optimum hydrogel for in vivo studies. In in vivo experiments, the silibinin permeability parameters were investigated through normal and UV-irradiated skin, anti-inflammatory property, and antioxidant effects after application of optimum hydrogel. RESULTS: The silibinin completely dispersed in the hydrogel, and FT-IR results showed that silibinin reacted with the chitosan and fucoidan and demonstrated a slow release pattern. The 50% and less than 70% of the drug-loaded on hydrogel were passed through normal and irradiated skin after 48 h, respectively. In vivo studies showed the effectiveness of optimized hydrogel in preventing the production of oxidative species and H2O2 after UVB radiation. Histological studies have shown that silibinin-loaded optimized hydrogel can prevent the hyperkeratosis, acanthosis, and infiltration of neutrophils into the dermis by UVB. CONCLUSION: Optimized hydrogel effectively reduced the inflammation mediators interleukin-22 and TNF-α, which signify tissue destruction. Therefore, silibinin-loaded hydrogel can be introduced as an effective sun-protective product.

Metformin loaded cholesterol-lysine conjugate nanoparticles: A novel approach for protecting HDFs against UVB-induced senescence.

Cellular senescence is one of the hallmarks of aging. Since senescence of dermal fibroblasts has been reported in vivo, reduction of the deleterious effects of these cells, has been considered an important intervention to counteract skin aging. Promising anti-aging effect of metformin has been reported. However, permeation of metformin due to its high hydrophilicity through skin epidermal barriers is limited. In this study, solid lipid nanoparticles (SLNs) of metformin were designed with the newly synthesized cholesterol-lysine conjugate as lipid for topical delivery of metformin. Characterization of SLNs strongly confirmed the effect of cholesterol-lysine conjugate on increasing entrapment of metformin. The designed SLNs with particle size of 283 nm and spherical morphology represented controlled drug release up to 18 days. Fluorescent tracking of SLNs on mice skin samples showed an increase in epidermal penetration. SLNs containing metformin showed anti-senescence effects on UVB-induced senescence of human dermal fibroblasts, this effect was confirmed by senescence-associated ß-galactosidase staining, RT q-PCR and cell cycle analyses. Furthermore, our drug-free SLNs showed anti-senescence effects, suggesting that they can be a suitable carrier for phytochemicals with anti-aging effect or other hydrophilic compounds which have constraints permeating skin.

Anti-microbial Effect and in Vivo Ocular Delivery of Ciprofloxacin-loaded Liposome through Rabbit's Eye.

Purpose: The main purpose of this study was to increase the concentration and bioavailability of Ciprofloxacin (CPX) in the rabbit eye by liposomal formulation. Methods: CPX- loaded liposomes with and without Carbomer 934 (carbomer) were prepared by a thin-layer hydration method. Liposomal formulations after evaluation for characters such as particle size and entrapment efficiency were used in in-vivo experimental for installation into the rabbit's eyes. This experimental study consisted of 10 rabbits divided into two groups. Group 1 (liposomes without coating) and group 2 (carbomer coated liposomes) received one drop per h of liposomes consists of 0.3% CPX in the right eye and commercial CPX eye drop in the left eye until 6 h. Aqueous humor and vitreous samples were collected from all rabbits at the baseline, 1, 3 and 6 h and the drug concentration determined by high pressure liquid chromatography (HPLC). On the other hand, minimum inhibitor concentration (MIC) and minimum bactericidal concentration (MBC) of CPX-loaded in liposomes were determined. Results: liposomal formulations increased ocular bioavailability of CPX around four-folds compared with a commercial CPX eye drop. The increase in the ocular bioavailability may be effective and help to treat bacterial endophthalmitis as well as can be used in prophylaxis of post-operative endophthalmitis. Conclusion: The concentrations of CPX on the aqueous humor and vitreous after liposomes application were more than MIC of CPX against pseudomonas auroginosa and staphylococcus aurous but for commercial eye drop was less than MIC. Therefore liposomes modified the pharmacokinetics of CPX and improved pharmacodynamics property.

Loratadine-Loaded Thermoresponsive Hydrogel: Characterization and Ex-vivo Rabbit Cornea Permeability Studies.

Poor bioavailability of ophthalmic drops is mainly due to drainage through the nasal-lacrimal duct and a very low permeability through corneal epithelium. The aim of our study was to prepare and characterize an ocular hydrogel of loratadine, as an example of a lipophilic drug, to increase drug concentration and residence time at the site of action in the eye. In this study, a 23 full factorial design was employed to design and compare the properties of eight different loratadine containing hydrogel formulations. Results showed a significant correlation between the swelling and porosity ratios of the hydrogels and the Pluronic percentage and Pluronic/carbomer ratio in the formulations. Moreover, the release profiles showed fast and sustained release of all the formulations. Evaluation of hydrogels structure by the FT-IR technique indicated that Pluronic interacts with hydroxyl and carboxylic groups in carbomer, which is the main reason of the hydrogel network formation and interacts with loratadine.The permeation of loratadine through rabbit cornea showed that drug permeation percentages for the F2 and F7 formulations were 15 and 70 folds more than that of the control.

Indomethacin electrospun nanofibers for colonic drug delivery: In vitro dissolution studies.

Generally, although the conventional drug delivery systems, such as using only pH-dependent polymers or time-dependent release systems are popular, the individuals' variations of physiological conditions usually lead to premature or imperfect drug release from each of these systems. Therefore, a combination of pH- and time-dependent polymers could be more reliable for delivering drugs to the lower GI tract such as colon. To this end, electrospinning method was used as a fabrication approach for preparing electrospun nanofibers of indomethacin aimed for colon delivery. Formulations were prepared based on a 32 full factorial design. Independent variables were the drug:polymer ratio (with the levels of 3:5, 4.5:5 and 6:5w/w) and Eudragit S:Eudragit RS w/w ratio (20:80, 60:40 and 100:0). The evaluated responses were drug release at pH 1.2, 6.4, 6.8 and 7.4. Combinations of Eudragit S (ES), Eudragit RS (ERS) and drug based on factorial design were loaded in 10ml syringes. Electrospinning method was used to prepare electrospun nanofibers from electrospinning solutions. Conductivity and the viscosity of the solutions were analyzed prior to electrospinning. After collection, the nanofibers were evaluated in terms of morphology and drug release. It was shown that the ratio of drug:polymer and polymer:polymer were pivotal factors to control the drug release from nanofibers. A formulation containing Eudragit S:Eudragit RS (60:40) and drug:polymer ratio of 3:5 exhibited the most appropriate drug release as a colon delivery system with a minor release at pH 1.2, 6.4 and 6.8 and major release at pH 7.4. Nanofibers resulted from this formulation were also more uniform and contained fewer amounts of beads. It was demonstrated that the electrospinning could be regarded as a modern approach for the preparation of colon drug delivery systems leading to marketable products.

Evaluation of the Antimicrobial Effect of Chitosan/Polyvinyl Alcohol Electrospun Nanofibers Containing Mafenide Acetate.

BACKGROUND: Chitosan, an important biodegradable and biocompatible polymer, has demonstrated wound-healing and antimicrobial properties. OBJECTIVES: This study aimed to evaluate the antimicrobial properties of mafenide acetate-loaded nanofibrous films, prepared by the electrospinning technique, using chitosan and polyvinyl alcohol (PVA). MATERIALS AND METHODS: A 3(2) full factorial design was used for formulating electrospinning solutions. The chitosan percentage in chitosan/PVA solutions (0%, 10%, and 30%) and the drug content (0%, 20%, and 40%) were chosen as independent variables. The release rate of mafenide acetate from nanofibrous films and their microbial penetration were evaluated. The antimicrobial activity of different nanofibrous film formulations against Staphylococcus aureus and Pseudomonas aeruginosa was studied. RESULTS: The results indicated that all nanofibrous films, with and without drug, can prevent bacterial penetration. Incorporation of mafenide acetate into chitosan/PVA nanofibers enhanced their antimicrobial activity against P. aeruginosa and S. aureus. CONCLUSIONS: Overall, the results showed that chitosan/polyvinyl alcohol (PVA) nanofibrous films are applicable for use as a wound dressing with protective, healing, and antimicrobial effects.

Development and evaluation of a solid self-nanoemulsifying drug delivery system for loratadin by extrusion-spheronization.

PURPOSE: Recently the liquid nanoemulsifying drug delivery systems (SNEDDS) have shown dramatic effects on improving oral bioavailability of poorly soluble drugs. The main purpose of this study was to prepare a solid form of self-nanoemulsifying drug delivery system of loratadin by extrusion-spheronization. The liquid SNEDDS are generally prepared in a soft or hard gelatin capsules which suffers from several disadvantages. Therefore incorporation of SNEDDS into solid dosage form is desirable to get together the advantages of SNEDDS and solid multiparticualte systems. METHODS: The SNEDDS was consisted of liquid paraffin, capriole, span 20, transcutol and loratadin as a poorly soluble drug. A multilevel factorial design was used to formulation of SNEDDS pellets, liquid SNEDDS (20 and 30%) was mixed with lactose, microcrystallin cellulose (40%) and silicon dioxide (0, 5 and 10%), and Na- crosscarmelose (0, 5 and 10%). The resulting wet mass transformed into pellets by extrusion-spheronization. The pellets were dried and characterized for size (sieve analysis), shape (image analysis), mechanical strength (friability test), droplet size (laser light scattering) and drug release rate (dissolution test). Selected SNEDDS pellets were also compared with conventional loratadin pellet or tablet formulation. RESULTS: The resulting SNE pellets exhibited uniform size and shape. Total friability of pellets did not affected by formulation variables. The in vitro release of SNE pellets was higher than the liquid SNE and powder tablets. CONCLUSION: Our studies demonstrated that extrusion-spheronization is a viable technology to produce self-emulsifying pellets in large scale which can improve in vitro dissolution with better solubility.

Indomethacin electrospun nanofibers for colonic drug delivery: preparation and characterization.

PURPOSE: The objective of this study was to prepare a suitable form of nanofiber for indomethacin using polymers Eudragit RS100 (ERS) and Eudragit S100 (ES) and to evaluate the effect of some variables on the characteristics of resulted electrospunnanofibers. METHODS: Electrospinning process was used for preparation of nanofibers. Different solutions of combinations of ERS, ES and indomethacin in various solvents and different ratios were prepared. The spinning solutions were loaded in 10 mL syringes. The feeding rate was fixed by a syringe pump at 2.0 mL/h and a high voltage supply at range 10-18 kV was applied for electrospinning. Electrospunnanofibers were collected and evaluated by scanning electron microscopy, differential scanning calorimetry and FTIR for possible interaction between materials used in nanofibers. The effect of solvent and viscosity on the characteristics of nanofibers also was investigated. RESULTS: Fiber formation was successful using a solvent ethanol and mixture of ERS and ES. Increase in viscosity of ethanolic solutions of ERS followed by addition of ES in the solution led to preparation of smooth fibers with larger diameters and less amounts of beads. DSC analysis of fibers certified that indomethacin is evenly distributed in the nanofibers in an amorphous state. FTIR analysis did not indicate significant interaction between drug and polymer. CONCLUSION: It was shown that drug-loaded ERS and ES nanofibers could be prepared by exact selection of range of variables such as type of solvent, drug: polymer ratio and solution viscosity and the optimized formulations could be useful for colonic drug delivery.

Percutaneous absorption of salicylic Acid after administration of trolamine salicylate cream in rats with transcutol(®) and eucalyptus oil pre-treated skin.

PURPOSE: This study was conducted to assess the effect of skin pre-treatment with Transcutol(®) and eucalyptus oil on systemic absorption of topical trolamine salicylate in rat. METHODS: Pharmacokinetic parameters of salicylic acid following administration of trolamine salicylate on rat skin pre-treated with either Transcutol(®) or eucalyptus oil were determined using both non-compartmental and non-linear mixed effect modeling approaches and compared with those of control group. RESULTS: Median (% of interquartile range/median) of salicylic acid AUC0-8hr (ng/mL/hr) values in Transcutol(®) or eucalyptus oil treated rats were 2522(139%) and 58976(141%), respectively as compared to the 3023(327%) of the control group. Skin pre-treatment with eucalyptus oil could significantly decrease extravascular volume of distribution (V/F) and elimination rate constant (k) of salicylic acid. CONCLUSION: Unlike Transcutol(®), eucalyptus oil lead to enhanced transdermal absorption of trolamine salicylate through rat skin.

Optimization of Ibuprofen Delivery through Rat Skin from Traditional and Novel Nanoemulsion Formulations.

The topical delivery of non-steroidal anti-inflammatory drugs (NSAIDS) such as Ibuprofen has been explored as a potential method of avoiding the first pass effects and the gastric irritation, which may occur when used orally. Ibuprofen is formulated into many topical preparations to reduce the adverse effects and simultaneously avoid the hepatic first-pass metabolism as well. However, it is difficult to obtain an effective concentration through topical delivery of Ibuprofen due to its low skin permeability. The aim of this study was to develop two types of nanoemulsions formulations and focused on the screening of Ibuprofen-loaded nanoemulsions and evaluating the influence of these types of nanoemulsions on the skin permeability of the drug. In both nanoemulsion formulations, oil was similar, but the surfactant and co-surfactant were different. The effect of independent variables on skin permeability parameters was evaluated using full factorial design. Results demonstrate that novel formulations were more effective as skin enhancer than traditional formulation. In case of the novel formulation, any increase in percentage of surfactant and co-surfactant had increasing effect on flux (Jss). On the other hand, the proportion of surfactant/co-surfactant (S/C) demonstrated reverse correlation with Jss. While, in traditional formulations, direct correlation was found between both variables, and Jss. Comparison between two types of nanoemulsion formulations revealed that, novel formulations were more effective as topical Ibuprofen carrier in contrast to traditional type due to lower amounts of surfactant and co-surfactant and less irritating effect.