Efficacy of Oral Mucoadhesive N-Acetylcysteine Tablets in Treatment of Recurrent Aphthous Stomatitis: A Randomized Double-Blind, Placebo-Controlled Clinical Trial.

Objectives: This study aimed to assess the efficacy of oral mucoadhesive N-acetylcysteine (NAC) tablets for treatment of recurrent aphthous stomatitis (RAS). Materials and Methods: Forty-nine patients with RAS were randomized to receive mucoadhesive NAC tablets (n=25) or placebo (n=24). Tablets were prescribed three times a day for 7 days in each group. Pain intensity was evaluated with visual analog scale (VAS) three times a day from day 1 to day 7. Also, patients were clinically examined on days 0 (before entering the study), 3, 5, and 7 using a metal caliper to measure the diameter of the lesions. The data were statistically analyzed and P<0.05 was considered statistically significant. Results: Regarding the VAS score, all participants in the treatment group showed complete recovery on day 7 (P<0.01). Also, the diameter of the lesions was significantly smaller in the treatment group than the placebo group at the end of the study (P<0.001). Conclusion: The results of this clinical trial showed for the first time that mucoadhesive NAC tablets can significantly decrease pain and the diameter of RAS lesions without any systemic complications.

Hyaluronic Acid-Coated Chitosan/Gelatin Nanoparticles as a New Strategy for Topical Delivery of Metformin in Melanoma.

Metformin is a multipotential compound for treating diabetes II and controlling hormonal acne and skin cancer. This study was designed to enhance metformin skin penetration in melanoma using nanoparticles containing biocompatible polymers. Formulations with various concentrations of chitosan, hyaluronic acid, and sodium tripolyphosphate were fabricated using an ionic gelation technique tailored by the Box-Behnken design. The optimal formulation was selected based on the smallest particle size and the highest entrapment efficiency (EE%) and used in ex vivo skin penetration study. In vitro antiproliferation activity and apoptotic effects of formulations were evaluated using MTT and flow cytometric assays, respectively. The optimized formulation had an average size, zeta potential, EE%, and polydispersity index of 329 ± 6.30 nm, 21.94 ± 0.05 mV, 64.71 ± 6.12%, and 0.272 ± 0.010, respectively. The release profile of the optimized formulation displayed a biphasic trend, characterized by an early burst release, continued by a slow and sustained release compared to free metformin. The ex vivo skin absorption exhibited 1142.5 ± 156.3 µg/cm2 of metformin deposited in the skin layers for the optimized formulation compared to 603.2 ± 93.1 µg/cm2 for the free metformin. Differential scanning calorimetry confirmed the deformation of the drug from the crystal structure to an amorphous state. The attenuated total reflection Fourier transform infrared results approved no chemical interaction between the drug and other ingredients of the formulations. According to the MTT assay, metformin in nanoformulation exhibited a higher cytotoxic effect against melanoma cancer cells than free metformin (IC50: 3.94 ± 0.57 mM vs. 7.63 ± 0.26 mM, respectively, P < 0.001). The results proved that the optimized formulation of metformin could efficiently decrease cell proliferation by promoting apoptosis, thus providing a promising strategy for melanoma therapy.

Wound Healing Properties of Pelargonium Graveolens L'Hér Extract Lipogel: In-Vivo Evaluation in an Animal Burn Model.

BACKGROUND: Pelargonium graveolens L'Hér has traditionally been used to reduce skin inflammation, and recent studies have confirmed antioxidant compounds in the plant's extract. The present study aimed to prepare a lipogel formulation from P. graveolens hydroalcoholic extract and evaluate its efficacy on the wound healing process in an animal model. MATERIAL AND METHODS: The aerial part extract of P. graveolens was prepared through percolation. Additionally, plastibase was prepared by mixing 5% of low-molecular-weight polyethylene with hot mineral oil (130°C). The extract (5%) was levigated in the mineral oil (5-15%) and dispersed in the cooled plastibase. The physical properties of the lipogel, thermal stability, and microbial limits were tested. Further, the effect of the lipogel in the wound healing rate was examined among male Wistar rats, and skin tissue samples were assessed histologically. RESULTS AND DISCUSSION: The results represented the best rheological and thermal stability characteristics in the formulation with 5% mineral oil (as the levigator). The lipogel-treated group had the least burn area compared to the silver sulfadiazine and negative control groups (p<0.05). The microscopic examination of tissue samples revealed increased collagen fiber production and maturation and significantly also faster epithelial repair among lipogel-treated rats than in the other two groups(p<0.05). CONCLUSION: The results indicated the significant therapeutic effects of P. graveolens lipogelon burn healing. The suitable physicochemical properties and the low lipogel production cost facilitate further scale-up studies.

Design and optimization of metformin-loaded solid lipid nanoparticles for neuroprotective effects in a rat model of diffuse traumatic brain injury: A biochemical, behavioral, and histological study.

BACKGROUND AND PURPOSE: Following traumatic brain injury, inflammation, mitochondrial dysfunction, oxidative stress, ischemia, and energy crisis can cause mortality or long-term morbidity. As an activator of AMP-activated protein kinase, metformin reduces the secondary injuries of traumatic brain injury by compensating for the lack of energy in damaged cells. But the blood-brain barrier prevents a hydrophilic drug such as metformin from penetrating the brain tissue. Solid lipid nanoparticles with their lipid nature can cross the blood-brain barrier and solve this challenge. so This study aimed to investigate the effect of metformin-loaded lipid nanoparticles (NanoMet) for drug delivery to the brain and reduce complications from traumatic brain injury. METHOD: Different formulations of NanoMet were designed by Box-Behnken, and after formulation, particle size, zeta potential, and entrapment efficiency were investigated. For in vivo study, Male rats were divided into eight groups, and except for the intact and sham groups, the other groups underwent brain trauma by the Marmarou method. After the intervention, the Veterinary Coma Scale, Vestibular Motor function, blood-brain barrier integrity, cerebral edema, level of inflammatory cytokines, and histopathology of brain tissue were assessed. RESULTS: The optimal formula had a size of 282.2 ± 9.05 nm, a zeta potential of -1.65 ± 0.33 mV, and entrapment efficiency of 60.61 ± 6.09% which released the drug in 1400 min. Concentrations of 5 and 10 mg/kg of this formula improved the consequences of trauma. CONCLUSION: This study showed that nanoparticles could help target drug delivery to the brain and apply the desired result.

Preparation and Evaluation of the Antibacterial Effect of Chitosan Nanoparticles Containing Ginger Extract Tailored by Central Composite Design.

Purpose: The ginger root extract has shown remarkable antimicrobial effects. Nanocarriers based on biodegradable polymers (like chitosan) are promising drug delivery vehicles for antibacterial compounds. In this study, aqueous and methanolic extracts of ginger root were prepared, loaded on chitosan nanoparticles (NPs), and their antimicrobial effects were investigated. Methods: The NPs were prepared using the ionic gelation technique. The central composite design model was employed to optimize the formulation variables and achieve the minimum particle size and maximum zeta potential. The total phenol content of the powdered extracts was determined. The antimicrobial activity of the NPs was evaluated by the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: The optimum size of NPs containing methanolic or aqueous extract were 188.3 and 154.7 nm, with a zeta potential of 29.1 and 32.1 mv, and entrapment efficiency percent (E.E.%) of 61.57±3.12% and 44.26±2.57%, respectively. Transmission electronic microscopy images confirmed the spherical particles in the low nanometer range. The phenol content of methanol extract was higher than the aqueous one (60.216 ± 1.83 and 39.835 ± 1.72 mg gallic acid equivalent/100 g), respectively). According to the results of the MIC and MBC, methanol extract NPs showed more potent antimicrobial effects, which seems to be associated with higher concentrations of phenolic compounds. The FTIR spectrophotometry showed no chemical interaction between the extracts and other ingredients. Conclusion: The results demonstrated that current NPs significantly increased the antibacterial effects of ginger extracts and could be selected for further evaluation.

Preparation, characterisation and comparative toxicity of nanopermethrin against Anopheles stephensi and Culex pipiens.

OBJECTIVES: To assess the effectiveness of nanopermethrin as a potential new formulation for pest and vector control. METHODS: Permethrin nanoparticles were prepared by the ionic gelation method and its structure and the formulations were designed using Box-Behnken statistical technique. The effect of independent variables (Chitosan/Permethrin ratio, tripolyphosphate quantity, sonication time) on the properties of nanoparticles was investigated to determine the optimal formulation. RESULTS: The size of the nanoparticles ranged from 135.27 ± 5.88 to 539.5 ± 24.01 nm and the insecticide entrapment efficiency per cent (EE%) ranged from 7.72 ± 1.36 to 63.59 ± 3.17%. Anopheles stephensi larvae were then bioassayed with the nanopermethrin and compared with the results of the bioassay with the mother molecule of permethrin using a standard WHO-recommended mosquito larval bioassay kit. LC50 with permethrin and nanopermethrin on larvae of An. stephensi were 0.125 and 0.026 ppm showing a 4.8 times difference. The LC50 for permethrin and nanopermethrin on Culex pipiens were 0.003 and 0.00032 ppm, respectively, showing a 9.4-fold difference. CONCLUSION: Nanopermethrin is much more potent than its mother molecule against larvae of An. stephensi and Cx. pipiens.

A promising technology for wound healing; in-vitro and in-vivo evaluation of chitosan nano-biocomposite films containing gentamicin.

Aim: This paper aims to study in-vitro and in-vivo evaluation of chitosan (CHI) biocomposite of gentamicin nanoparticles (GNPs) for wound healing. Methods: In this study, CHI nanoparticles (NPs) were prepared using the ionic gelation technique. GNP biocomposites were examined on the excision wound model in Wistar rats to determine the in-vivo efficiency. Results: The diameter and zeta potential of NPs were between 151-212.9 nm and 37.2 - 51.1 mV, respectively. The entrapment efficiency was in an acceptable range of 36.6-42.7% w/w. The release test information was fitted to mathematical models (Zero, First order, Higuchi, and Korsmeyer-Peppas), and according to calculations, the kinetics of drug release followed the Korsmeyer-Peppas model. A comparison of thermograms revealed that the drug was present in the formulation in a non-crystalline form. Conclusion: Histological studies of the wound showed that the rate of skin tissue repair was higher in the GNP biocomposite treatment group than in the others.

Solid Dispersion Pellets: An Efficient Pharmaceutical Approach to Enrich the Solubility and Dissolution Rate of Deferasirox.

Deferasirox (DFX) is an oral iron-chelating agent and classified into class II of the Biopharmaceutics Classification System. Low bioavailability of the drug due to insufficient solubility in physiological fluids is the main drawback of DFX. The idea of the current study was to explore the potential of solid dispersion (SD) as an effective method to improve the dissolution rate of DFX in pellets. The SDs were made by the solvent evaporation technique using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K25 with different drug-to-carrier ratios. Then, the dispersion was milled and mixed with other components and the mixture layered on sugar-based cores by pan coating technique. The pellets were evaluated in terms of size distribution, morphology (SEM), and dissolution behaviour. Drug-polymer interactions were studied using differential scanning calorimetry (DSC), X-ray diffraction study (XRD), and Fourier transformation infrared (FTIR) spectroscopy. The pellets coated with SD showed a remarkable rise in the solubility of DFX than that of free drug-loaded pellets. The dispersion with PVP K25 showed a faster dissolution rate as compared to other mixtures. The DSC and XRD analysis indicated that the drug was in the amorphous state when dispersed in the polymer. The FTIR studies demonstrated any ruled out interaction between drug and polymer. The SEM showed smoothness on the surface of the pellets. It is resolved that the SD method considerably enriched the dissolution rate of DFX in pellets, which can also be utilized for other poorly water-soluble drugs.

Methylene blue-loaded niosome: preparation, physicochemical characterization, and in vivo wound healing assessment.

Following skin injury, the overproduction of reactive oxygen species (ROS) during the inflammatory phase can cause tissue damage and delay in wound healing. Methylene blue (MB) decreases mitochondrial ROS production and has antioxidant effects. The authors aimed to prepare MB-loaded niosomes using the ultra-sonication technique as a green formulation method. A Box-Behnken design was selected to optimize formulation variables. The emulsifier to cholesterol ratio, HLB of mixed surfactants (Span 60 and Tween 60), and sonication time were selected as independent variables. Vesicle size, zeta potential (ZP), and drug entrapment capacity percentage were studied as dependent variables. The optimized formulation of niosomes showed spherical shape with optimum vesicle size of 147.8 nm, ZP of - 18.0 and entrapment efficiency of 63.27%. FTIR study showed no observable interaction between MB and other ingredients. In vivo efficacy of optimized formulation was evaluated using an excision wound model in male Wistar rat. Superoxide dismutase (SOD, an endogenous antioxidant) and malondialdehyde (MDA, an end product of lipid peroxidation) levels in skin tissue samples were evaluated. After 3 days, MDA was significantly decreased in niosomal gel-treated group, whereas SOD level was increased. Histological results indicate rats that received niosomal MB were treated effectively faster than other ones. Graphical abstract.

Development and Optimisation of Spironolactone Nanoparticles for Enhanced Dissolution Rates and Stability.

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ∼170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability.