Cell organelle-shaped liposomes: A novel approach to present the stable intracellular drug delivery systems

Caveolae are lipid raft-enriched flask-shaped, expose in the plasma membrane of various cell types. It has become clear now that caveolae and their caveolin “marker proteins” are associated in a several cellular procedures including endocytosis, lipid homeostasis, signal transduction, and tumorigenesis. Caveolin has been shown to have high binding affinity for cholesterol and sphingolipids. Caveolin oligomers construct filamentous networks that are believed to stabilize the membrane. Liposomes are the well-known drug delivery systems with spherical shape that can be produced from natural non-toxic phospholipids and cholesterol. Liposomes have been used as a considerable tool in biology, biochemistry, medicine, and drug delivery. The utilization of liposomes as a drug-delivery system has become more attractive in carrying systemically administered drugs with narrow therapeutic windows. The similarity between plasma membrane and liposomes from several points of view gives hope that the incorporation of caveolin in the phospholipid bilayer structures of liposomes can result in tightening and therefore stabilizing and long circulation of these structures.</p

Chitosan Dextran Microparticles as the Potential Carrier for Colon Specific Delivery of 5- Fluorouracil

Introduction: Colorectal cancer is one of the most commonly diagnosed cancers in the world. The main and classic treatment of this cancer is 5-fluorouracil (5-Fu) that its cytotoxicity and low systemic absorption restricted its therapeutic efficacy. To overcome these problems, mucoadhesive and colonic microbially degradable formulations based on chitosan and dextran sulphate hydrogels could be effective. Methods and Results: 5-Fu loaded hydrogel microparticles were formed via polyelectrolyte complexation technique using chitosan and dextran sulphate solutions. It was optimized by a systematic multi-objective optimization approach in terms of the particle size and loading efficiency of the resulting microparticles. Under this condition, the molecular weight of chitosan and 5-Fu concentration are the two factors which significantly influence the particle size and loading efficiency, respectively. Then the optimized microparticles were prepared and were characterized based on particle size, zeta potential, drug loading and drug release behavior. Finally the cytotoxicity of optimized microparticles was assessed by MTT assay (SW742 cell line) compare to free drug solution. Therefore, spherical particles of 51.33±0.95 μm mean diameter and a narrow size distribution were obtained under optimal conditions. The zeta potential, loading efficiency and loading capacity of optimized microparticles were 18.1±0.87mv, 26.96±0.38 and 13.12±0.65%, respectively. The in vitro drug release profile was fitted on Higuchi model and the cytotoxicity MTT results indicated the higher cytotoxicity of studied formulation on cells compare to free drug. The hydrogel microparticles were further lyophilized to prepare the enteric coated tablets and all tests endorsed that the coating process was suited. Conclusions: The designed formulations have provided appropriate properties and offer a potential mean for colon specific delivery of 5-Fu via oral administration

The Potential Role of Metformin in Relieving Acne Vulgaris by Modifying the Impaired Cellular Signaling Pathway, Responsible for Acne Pathogenesis

&nbsp;Introduction: Acne vulgaris is one of the most common skin disorders, which various factors are involved in its pathogenesis. Recent investigations on intracellular signaling pathway show that the over expression of mTORC1 complex (mammalian target of rapamycin), leads to increased sebum production and altered keratinization, therefore it has an important role in acne pathogenesis. Another studies also showed that the expression of mTORC1 is significantly increased in the skin cells of the patients, which confirm the linkage between acne pathogenesis and mTORC1 over expression. The aim of this study is to represent a way to confront the impaired endocrine signaling, in order to relieve the acne symptoms. Methods and Results: The linkage between acne pathogenesis and endocrine signaling pathway was demonstrated through the collected signaling data from popular scientific databases such as www.Kegg.Jp. Insulin resistance is one of the major factors that leads to mTORC1 over expression. Metformin, a biguaniide that increases the cell's sensitivity to insulin, is the drug of choice for this condition, as it is able to suppress mTORC1 over expression through AMPK (5' adenosine monophosphate-activated protein kinase) activation. So, applying a topical form of the drug on acne spots, may lead to relieve the symptoms. Topical semi solid formulation of metformin was prepared with the use of suitable thickening polymers and formulation was optimized through the point of viscosity and rheological behaviors of the aqueous gel, so the optimum ratio of the thickening polymers was determined. Conclusions: Signaling pathways show that acne pathogenesis is mediated through mTORC1 over activation, so we were aimed to design a formulation which is able to suppress this over expression in order to relieve acne symptoms. Metformin, formulated in a topical form, is the drug of choice, as it is a safe drug which can suppress the mTORC1 over expression through AMPK activation in the skin of acne patients

Preparation and evaluation of a mastic gum Peel-off mask as a skin-refreshing product

As the first link in the ecological chain, plants play an important role in human life. Their application as a group of ingredients in cosmetic products is one of the most important issues in the field of specialized skin and beauty management. Among these plants, the mastic plant and the preparation, gum, with the scientific name Pistacia lentiscus L., (Anacardiaceae family) are interesting for producing cosmetic products. In the present study, Mastic gum has been evaluated in terms of preparation for a Peel-off gel mask as well as assessment of physicochemical and phytochemical properties. Analyses such as Gas chromatography fingerprint and infrared spectroscopy were performed, and then the gum gel sheet mask formulation was prepared. The main compound in the analysis of GC/MS results of plant essential oil was α-Pinene with 65.78%. Following the preparation of the peel-off mask, the pharmaceutical evaluations related to the product including product color and odor test (organoleptic), product stability test, pH determination, conductivity, spreadability, and microbial total count were performed. The obtained outcomes showed the appropriate characteristics of the product for topical application. It is considerable that by completing the clinical processes and fulfilling the standardization procedure of the active ingredient and formulation, this mask can be presented as a suitable candidate in the cosmetic field and available in the market

Solid-phase nano extraction as a green approach for the analyte isolation

Today rapid and reliable analytical method for determining the trace level of targeted analytes in biological analysis and different fields is an essential object in analysis. So we try to focus on novel methods suggested for improving solid-phase microextraction based on novel drug delivery systems, especially nanoparticles. Nanoparticles like (dendrimer, carbon-based nanoparticles, magnetic and mesoporous nanoparticles, …) and their application as a new sorbent combined with different methods such as solid microextraction and liquid microextraction techniques are discussed in this article. These nano sorbents induced the potentials like selectivity and sensitivity for these methods. Furthermore, this nano extraction caused the lower consumption of hazardous solvent and reduced the total time needed for the extraction procedure, especially in biological analysis. The beneficial effects of nanoparticles indicated that a meaningful future was expected for their application. These new sorbents can be evolved the analytical methods and create reliable and rapid analytical methods

A reversed-phase high performance liquid chromatography approach for analysis of 5-Fluorouracil

A reproducible, sensitive, accurate and selective high performance liquid chromatographic (HPLC) method with ultraviolet absorbance detection has been developed and validated to quantitate 5-Fluorouracil (5-FU), an antimetabolite chemotherapeutic agent used in treatment of colorectal cancer as a drug of choice. Chromatographic separations were performed on a C18 column (Eurosphar 100-5, 150 mm × 4.6 mm) as the reversed stationary phase, eluted with a mobile phase composed of deionized water and methanol (95:5) with the flow rate of 1.0 mL/min. The UV wavelength was set at 261nm. The method produced linear responses throughout 5-fluorouracil range of 25-500 ng/ml with a correlation coefficient of 0.998. A limit of quantitation (LOQ) was established at 25 ng/ml. The within-day and between-day precision and accuracy were both in acceptable ranges. The outcomes of these tests indicate a proper separation efficacy as well as accuracy and sensivity of method which is a potential tool in many pharmaceutical studies such as drug delivery of this anti-cancer agent. </p

A Reversed-phase High Performance Liquid Chromatography (HPLC) method for bio-analysis of Methotrexate

Methotrexate (MTX) is a chemotherapeutic agent used in treatment of many disorders including autoimmune diseases and cancers. The availability of a reliable analysis method for drug assay in biological fluids of interest  is  a  prerequisite  for  all  pharmacokinetic  studies  in  humans  or  animal  models. Considering the complex matrices of the biological specimens as well as the low concentrations of the majority of the drugs in biological fluids, the development of an available while sensitive method for the bioanalytical studies is often a challenging issue.For drug assay in aqueous, plasma, animal brain and liver tissue environments in a concentration range of 25-600 ng/ml, a reverse phase high performance liquid chromatography (RP-HPLC) was developed.System suitability tests were indicating a method with acceptable analytic separation efficiency and peak shape proving method’s selectivity. Limit of detection (LOD) and limit of quantification (LOQ) determined to be 10 ng/ml and 25ng/ml, which reflect method sensitivity. Regression analysis showed a linear correlation between area under curve (AUC) of peaks and corresponding MTX concentrations. The within-day and between-day precision and accuracy was both in acceptable ranges. Recovery index of method for median concentration (200 ng/ml) is also about 74%.The developed method was accorded to the acceptable criteria of analytical method validation. The sensitivity of the method in all the tested matrices made the method suitable in terms of detection and quantitation of low concentration samples throughout the study. Also, the assay method had fairly short run-time and lacks any significant interference. </p

Various production and service models on small-scale of natural products as a new job opportunity for pharmacists.

Introduction: pharmacists' job opportunities in Iran are limited to the presence in the industry, pharmacy, hospital, research-centers and faculty of universities. The need of our community to the pharmacist is quantitatively 32 pharmacists per 100,000 people. Every year, 1000 pharmacists graduate in Iran; but there are not enough adequate employment opportunities for them. Given the huge costs of establishing and purchasing a pharmacy and a factory. Job opportunity for pharmacists should be created based on entrepreneurship principles. These opportunities can be defined in the format of designing knowledge-based models that are managed by the pharmacist. There are remarkable amounts of natural products required by healthcare providers on a small scale every day. Manufacturing these products is not cost-effective for a large industrial complex. Small-median enterprises model is one of the reasons for the success of the BRICK countries based on the small-scale chain production ultimately make a huge economic network structure­­ with high profitability.Methods and Results: Regulations of Health Ministry, the GMP principles for herbal productions, regulations of nutrition supplements registration, the process of issuing the production license, the process of issuing the establishment permit, the minimum requirements for establishing the units of medicinal plants packaging and production of plant extracts, the regulation for getting packaging and production license for plant products,supportive-policy package, industry relations with the university in the area of food and drug, regulations and guidelines for registration and establishment of knowledge-based companies, all were investigated.According to the existing criteria, the following proposed models can be presented:1) Small production with maximum 10 employees; including solids, semisolid and liquids production departments.2)Production workshop model outside the city with maximum 50 employees. 3) Providing consultation and training services in the field of medicine. Conclusions: As the pharmaceutical community need to the job that by applying a not-so-great capital to have a proper efficiency, and the pharmacist to use his knowledge, a set of products as a network can besides providing these needed items, provide the country with natural products. Therefore, the facilities to create new pharmaceutical job opportunity as well as holding empowerment courses for pharmaceutical students in this field are required

Phenotype and Genotype Heterogeneity of PLA2G6-Associated Neurodegeneration in a Cohort of Pediatric and Adult Patients

BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6. METHODS: An extensive review of the patients\u27 data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease\u27s underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach. RESULTS: Eighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% - 1.10, and upper 95% - 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype-phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6. CONCLUSION: PLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype