Preparation of Diltiazem Topical Gel for the Treatment of Anal Fissure and In-vitro, Ex-vivo Drug Release Evaluations

Abstract: Introduction: Anal fissures are small tears in the lining skin of the anus presenting with typical symptoms of pain and bleeding during defecation. Several new forms of medicines such as glyceryle trinitrate (GTN) ointments and diltiazem, a calcium channel-blocking agent, have been recently used for the treatment of these fissures. Diltiazem relaxes the muscle of anal sphincter and consequently increases blood flow to promote healing. It does not have GTN side effects like headache, anal burning and hypotension. The objective of this study was to formulate a suitable topical gel from diltiazem and then to investigate its physicochemical stability and also the drug release profiles from the bases. Methods: Various formulations of gel base including Guar 1.25%, Tragacanth 1.5%, HPMC 1%, and HPMC 1.5% were prepared and in vitro release and penetration characteristics of diltiazem from each preparation were studied through a hydrophilic dora pore diffusion barrier and membrane excised rat skin using Franz cell over a period of 5 hours. The amount of drug released from topical preparations was determined spectrophotometrically at ? max=236 nm. Stability studies and shelf life assessments were performed too. Results: Gel formulations containing HPMC, Guar and Tragacanth presented both good chemical and physical stabilities. The rates of cumulative drug release from HPMC 1%, HPMC 1.5%, Guar 1.25% and Tragacanth 1.5% bases using synthetic membrane were 89.7%, 76.7%, 94.9% and 66.1% respectively. For excised rat skin test, the cumulative percent of penetrated drug at the end of each experiment were 52.7 %, 50.9%, 64.6% and 42.6% for HPMC 1%, HPMC 1.5%, Guar 1.25% and Tragacanth 1.5% bases respectively. Conclusion: The comparative study showed that the percent of drug release from synthetic membrane was more than the percent of penetrated drug through excised rat skin for all bases (P<0.05). It was concluded that the kinetics of diltiazem release in vitro was not affected by the kind of gel forming agent and for all of the formulations, Higuchi’s kinetic model was suitable to explain their kinetics. Keywords: Diltiazem, Topical gel, Anal fissur

Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid�Induced Colitis in Rats

Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid�induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid�induced colitis. © 2015, © The Author(s) 2015

Keratinocyte exosomes for topical delivery of tofacitinib in treatment of psoriasis: an in vitro/ in vivo study in animal model of psoriasis

Objective: The present study aimed to formulate and study effectiveness of an exosomal delivery system of tofacitinib (TFC). Methods: TFC was loaded by different methods in exosomes and then characterized for particle size, zeta potential, drug loading efficiency, and release efficiency. By comparing these parameters, the probe sonication method was chosen to load TFC into exosomes. The MTT assay was used to compare the cytotoxicity of the free drug with the TFC-loaded exosomes (TFC-Exo), and Real-time PCR was used to determine the expression levels of several genes involved in psoriasis expressed in the A-431 keratinocyte and their suppression after treatment. Animal model of psoriasis was induced in BALB/c mice by imiquimod and the efficacy of free TFC, and TFC-Exo were studies on macroscopic appearance and histopathological symptoms. Results: Exosomes encapsulating TFC showed lower cytotoxicity in MTT assay, higher suppression the expression of TNF-a, IL-23, IL-6, and IL-15 genes in real-time PCR and better therapeutic effect on animal models compered to free TFC. Conclusions: This method of drug delivery for TFC may be effective on enhancing its therapeutic effects and reduction its side effects favorably in chronic administration

Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid) Bioadhesive Nanoparticles

The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1), iv solution of sCT (5 μg·kg−1), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly

Anti-inflammatory effect of Pistacia atlantica subsp. kurdica volatile oil and gum on acetic acid-induced acute colitis in rat

Background and objectives: Baneh tree or Pistacia atlantica subsp. kurdica is an endemic plant of Iran which belongs to Anacardiaceae family. It has various traditional uses including astringent and anti-diarrheal as well as improving some of the symptoms of gastrointestinal upsets. In this study we decided to investigate the effects of various fractions of baneh gum with different doses in an animal model of ulcerative colitis as one of the important chronic inflammatory bowel diseases of the gastrointestinal tract. Methods: The volatile oil and aqueous baneh gum suspensions were prepared and the constituents of the volatile oil were analyzed by GC/MS. They were used to treat colitis induced by acetic acid 4% in rats. Three doses of gum (100, 200 and 400 mg/kg) were administered both orally (p.o.) and intra-rectally (i.r.) while volatile oil was administered p.o. with doses 100, 200 and 400 µl/kg for four constitutive days. Anti-inflammatory effects of the test compounds were compared with oral prednisolone and hydrocortisone enema. Wet colon weight/ length ratio and tissue damage scores and area as well as indices of colitis and tissue myeloperoxidase activity were evaluated for each specimen. Results: Alpha-pinene was the main constituent of baneh volatile oil (41.23%). We observed therapeutic effects in applied doses of oral gum as well as volatile oil to reduce all indices of colitis and myeloperoxidase activity. Unlike the oral form of gum, its rectal administration was not significantly effective to improve colitis. Conclusion: This research has proved the anti-inflammatory potential of oral gum of Pistacia atlantica subsp. kurdica and its volatile oil in an experimentally induced colitis

Clinical Evaluation of a Topical Doxepin Cream (5%) in Treatment of Eczema

ABSTRACT: Introduction & Objective: Eczema is one of the most common pruritic skin disorders for which various treatments are used to relieve the symptoms. There are several reports about the efficacy and in part safety of topical doxepin in the treatment of pruritic dermal diseases. However, lack of a suitable topical preparation from this drug in our country persuaded us to design the present trial. Materials & Methods: A randomized, double blind, placebo- controlled and multi- centeral clinical trial was carried out in Isfahan during the years of 1383-84 by using 60 volunteers and both the drug and placebo were given QID for 8 days. The efficacy, side effects and their relevance to sex and age of subjects were assessed before, during and after the treatment. The data were analyzed using non-parametric tests including Mann-Whitney, Wilcoxon, and Kendall Tau where appropriate. Results: Results indicated that doxepin cream effectively reduced disease symptoms including pruritus (75.5%), inflammation (43.8%) skin dryness (37.5%) exudates (59.5%), lichenification (41.5%), and eczema (41.5%) after the course of treatment (the day of 8). Same results were obtained by using placebo. Stinging as an adverse effect was occurred in both the drug (30 %) and placebo (27%) groups. Conclusion: Although there was no significant difference between the two groups, it can be concluded that doxepin cream (5 %) is effective in depressing the signs and symptoms of pruritic skin disorders. A larger clinical trial is needed to evaluate the efficacy and safety of the product more precisely