Preparation and Evaluation of Tretinoin Microemulsion Based on Pseudo-Ternary Phase Diagram

Purpose: The aim of the present research was to formulate a transparent microemolsion as a topical delivery system for tretinoin for the treatment of acne. Methods: Microemulsion formulations prepared by mixing appropriate amount of surfactant including Tween 80 and Labrasol, co-surfactant such as propylene glycol (PG) and oil phase including isopropyl myristate – transcutol P (10:1 ratio). The prepared microemolsions were evaluated regarding their particle size, zeta potential, conductivity, stability, viscosity, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), refractory index (RI) and pH. Results: The results showed that maximum oil was incorporated in microemolsion system that was contained surfactant to co-surfactant ratio (Km) of 4:1. The mean droplets size range of microemulsion formulation were in the range of 14.1 to 36.5 nm and its refractory index (RI) and pH were 1.46 and 6.1, respectively. Viscosity range was 200-350 cps. Drug release profile showed 49% of the drug released in the first 8 hours of experiment belong to ME-7. Also, Hexagonal and cubic structures were seen in the SEM photograph of the microemulsions. Conclusion: physicochemical properties and in vitro release were dependent upon the contents of S/C, water and, oil percentage in formulations.Also, ME-7 may be preferable for topical tretinoin formulation

Pesticide Consumption in Greenhouses; a Case Study of Kashan Region

Aims: In regard to increasing greenhouse area in Iran followed by increased use of pesticides and contaminated crops, this study aimed to determine the frequency and types of consumed pesticides in Kashan region, Iran, greenhouses. Instrument & Methods: In this descriptive study in 2011-2012, samples was entered by census method. At the first step, a list of greenhouses was obtained from agricultural organization, 39 active greenhouses were detected, thereafter the questionnaires have been completed in detail by direct interview; obtained data were analyzed in SPSS 23 by descriptive statistics. Findings: 87.1 of greenhouses used chemical methods for controlling pest and diseases of products and 43.5 used non-chemical methods. The most frequent used chemical pesticides were Deltamethrin (37.9) and Permethrin (28.3) as pyrethroid insecticides, Diazinon (23.1) as an organophosphate insecticide and Carbendazim (23.2) as a fungicides. Conclusion: 87.1 of the greenhouses’ owners of Kashan region, Iran, use chemical pesticide for pest control

Effect of the Various Solvents on the In Vitro Permeability of Vitamin B12 through Excised Rat Skin

Purpose: To investigate the effect of different solvents on the in vitro skin permeability of vitamin B12.Method: Vitamin B12 (B12) permeability experiments through rat skin pretreated with various solvents namely, propylene glycol, oleoyl macrogol-6-glycerides, propylene glycol monocaprylate and oleic acid, were performed in Franz diffusion cells and compared with hydrated rat skin as control. The permeability parameters evaluated include steady-state flux (Jss), lag time (Tlag), permeability coefficient (Kp) and diffusion coefficient (D). The solvents’ permeability enhancement mechanisms were investigated by comparing of changes in peak position and their intensities of assymmetric (Asy) and symmetric (Sym) C-H stretching, and C=O stretching absorbance using Fourier transform infrared spectroscopy (FTIR), as well as by comparing mean transition temperature (Tm) and their enthalpies (ΔH) using differential scanning calorimetery (DSC).Results: All the solvents significantly decreased diffusion coefficient (p < 0.05), with capryol showing the greatest enhancement ratio (ERD) based on diffusion coefficient followed by labrafil, oleic acid and propylene glycol. Flux enhancement ratio (ERflux) for all the solvents was < ERD. The solubility of B12 in stratum corneum was the rate-limiting step in partitioning. All solvents with different lipophilic properties decreased drug solubility in the stratum corneum and hence lowered partitioning and flux. FTIR and DSC results showed lipid fluidization and extraction by labrafil and capryol, disruption of lipid structure and fluidization by oleic acid, and interaction with stratum corneum keratin by propylene glycol.Conclusion: Water is a suitable topical vehicle for B12 as it can increase partitioning and diffusion through rat skin.Keywords: Percutaneous absorption, Enhancer, Vitamin B12, Skin permeation, Diffusion coefficient, Flux, Enthalp

Enhanced Corneal Permeation of Pilocarpine Using Liposome Technology

A novel liposomal pilocarpine formulation as an ophthalmic drug delivery system has been designed to treat patients with glaucoma. The purpose of the present study was to formulate and evaluate liposomes loaded with pilocarpine and to evaluate permeation through rabbit cornea. Liposomes containing pilocarpine were prepared using thin film method. The quantities of soya lecithin and cholesterol were changed to enhance the encapsulation of the drug. The physicochemical properties of the prepared liposomes were evaluated according to their viscosity, pH, particle size, in vitro drug release, and transcorneal rabbit permeation. Dialysis membrane method was utilized to assess drug release profile. The results indicated that the mean particle sizes of liposomes were 120.5-212 nm and the pH and viscosity of formulations were in the range of 6.30-6.63 and 43.85-80.1 cps, respectively. According to the release study results, maximumally 60% of the drug released from liposomal formulations after 24 hours of the experiment. Also, the cumulative percentage of the drug permeated through rabbit cornea was differing from 3.86 to 14.9%. Irrespective from the composition and characteristics of the different liposomal formulations, they significantly increased the drug partitioning, permeability coefficient and flux of pilocarpine in rabbit cornea ex vivo model in comparison to control drug solution. The present study proved that any alteration in composition and nature of pilocarpine liposomal formulations may affect the drug permeability parameters through corneal membrane and also physico-chemical properties. It is probably due to the change in corneal structure in the presence of different liposomes composition

Guidance on safety evaluation of sources of nutrients and bioavailability of nutrient from the sources

Whenever new substances are proposed for use as sources of nutrients in food supplements, foods for the general population or foods for specific groups, EFSA is requested by the European Commission to perform an assessment of their safety and of the bioavailability of the nutrient from the proposed source. This guidance describes the scientific data required to allow an evaluation of the safety of the source within the established framework for risk assessment of food additives and novel food ingredients and the bioavailability of the nutrient from this source. This document is arranged in five main sections: one on technical data aimed at characterising the proposed source and at identifying potential hazards resulting from its manufacture and stability in food; one on existing authorisations and evaluation, providing an overview of previous assessments on the proposed source and their conclusions; one on proposed uses and exposure assessment section, allowing an estimate of the dietary exposure to the source and the nutrient based on the proposed uses and use levels; one on toxicological data, describing approaches which can be used to identify (in conjunction with data on manufacture and composition) and to characterise hazards of the source and any relevant breakdown products; the final section on bioavailability focuses on determining the extent to which the nutrient from the proposed source is available for use by the body in comparison with one or more forms of the same nutrient that are already permitted for use on the positive lists. This guidance document should replace the previous guidance issued by the Scientific Committee for Food and published in 2001

Targeted Nano-Drug Delivery System to Colon Cancer

Cancer has been considered as the most cause of death in world. Employing of nanocarriers as drug delivery systems provide a platform for delivering drugs with increasing the anti-cancer efficacy, enhancing bioavailability of drugs, reducing side effects, enhancing the circulation half-life of drugs, improving the distribution of drugs and overcoming drug resistance. A number of nanocarriers have been studied as drug delivery systems for improving the treatment of cancer including liposomes, micelle, polymeric nanoparticles, carbon nanotubes, dendrimers, solid lipid nanoparticle (SLN) and nanostructure lipid carrier (NLC). In order to enhance recognition and internalization of nanocarriers by the target tissues, their surfaces can be modified with targeting ligands such as integrins, transferrin, folic acid, polysaccharides and antibodies. In this chapter, we are going to introduce the targeted nanocarriers for improving the cytotoxic action of drugs with further attempt of decreasing dose to achieve higher anticancer activity. Targeted nanocarriers would provide a promising therapeutic approach for cancer

IN VITRO SCREENING OF ANTI-CANDIDA ACTIVITY OF SAPONINS EXTRACTED FROM GLYCYRRHIZA GLABRA AND QUILLAJA SAPONARIA

Objective: In recent years, the incidences of opportunistic fungal pathogens have increased and development of fungal resistance to antifungal drugs is a global concern. Therefore, it is important to identify new antifungal agents. Saponins are secondary metabolites that are found in various plant species and show antifungal activity. The aim of the study was to evaluate antifungal activity of saponin extracted from the Glycyrrhiza glabra against Candida species (Candida albicans, Candida tropicalic and Candida glabrata). Antifungal activity Quillaja saponaria total saponin (QST) was also evaluated. Methods: The roots of the plant were dried, powdered and def-fatted with petroleum ether in a soxhlet apparatus. The air dried powder was successively extracted with methanol, n-butanol and diethyl ether. The antifungal activity of the saponins was carried out using well diffusion method and also the value of minimum inhibitory concentrations (MIC) was calculated. Clotrimazole was used as positive controls to determine the sensitivity of the species. Results: According to the results, C. albicans, and C. tropicalic were sensitive to the saponins of G. glabra, and Q. saponaria, while saponin isolated from G. glabra just could inhibited the growth of C. glabrata. Conclusion: In vitro studies have demonstrated that saponins extracted from G. glabra, and Q. saponaria can serve as potential candidates for the development of new antifungal agents.     Key words: Saponin, Glycyrrhiza glabra, Quillaja saponaria, Anti-Candida activit

Preparation and Microstructural Characterization of Griseofulvin Microemulsions Using Different Experimental Methods: SAXS and DSC

Purpose: The objective of the present study is to formulate and evaluate a new microemulsion (ME) for topical delivery of griseofulvin. Methods: The solubilities of griseofulvin in different combinations of surfactant to co-surfactant (S/Co ratio) were determined. Accordingly, based on their phase diagrams, eight microemulsions were formulated and then evaluated with respect to their particle size, surface tension, viscosity, conductivity, zeta potential and stability. Their release behavior, Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), refractory index (RI), pH and Small-angle-X-ray scattering (SAXS) were also assessed. Results: The results indicated that the mean droplet size of the MEs ranged from 30.9 to 84.3 nm. Their zeta potential varied from -4.5 to -20.8. Other determined characteristics were viscosity: 254-381 cps, pH: 5.34-6.57, surface tension: 41.16- 42.83 dyne.cm-1, conductivity: 0.0442 – 0.111 ms.cm-1. The drug release was in the range of 22.4 to 43.69 percent. Also, hexagonal, cubic and lamellar liquid crystals were observed in SAXS experiments. Conclusion: It can be concluded that any alteration in MEs constituents directly affects their microstructure, shape, droplet size and their other physicochemical properties

The design of naproxen solid lipid nanoparticles to target skin layers

The aim of the current investigation was to produce naproxen solid lipid nanoparticles (Nap-SLNs) by the ultrasonication method to improve its skin permeation and also to investigate the influence of Hydrophilic-lipophilic balance (HLB) changes on nanoparticles properties. The properties of obtained SLNs loaded with naproxen were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). FT-IR was also used to investigate any interaction between naproxen and the excipients used at the molecular level during the preparation of the SLNs. The performance of the formulations was investigated in terms of skin permeation and also the retention of the drug by the skin. It was found that generally, with increasing the lipid concentration, the average particle size and polydispersity index (PDI) of SLNs increased from 94.257 ± 4.852 nm to 143.90 ± 2.685 nm and from 0.293 ± 0.037 to 0.525 ± 0.038 respectively. The results also showed that a reduction in the HLB resulted in an increase in the PDI, particle size, zeta potential and entrapment efficiency (EE %). DSC showed that the naproxen encapsulated in the SLNs was in its amorphous form. The peaks of prominent functional groups of naproxen were found in the FT-IR spectra of naproxen-SLN, which confirmed the entrapment of naproxen in the lipid matrix. FT-IR results also ruled out any chemical interaction between drug and the chemicals used in the preparation of SLNs. The amount of naproxen detected in the receptor chamber at all the sampling times for the reference formulation (naproxen solution containing all surfactants at pH 7.4) was higher than that of the Nap-SLN8 formulation. Nap-SLN8 showed an increase in the concentration of naproxen in the skin layer with less systemic absorption. This indicates that most of the drug in Nap-SLN8 remains in the skin which can reduce the side effect of systemic absorption of the drug and increases the concentration of the drug at the site of the action

Formulation of a New Generation of Liposomes from Bacterial and Archeal Lipids

Purpose: To evaluate the application of bacterial liposomes and archaeosomes as a novel drug delivery system for in vitro cytoplasmic delivery of molecules into cancer cells.Methods: Bacterial membrane lipids were extracted using chloroform and methanol. Bacterial liposomes and archaeosomes of E. coli, Acidianus brierleyi and Sulfolobus acidocaldarius were prepared using film method and their trailing in cancer cells (HT-29) was evaluated by carboxyfluorescein (CF). Their morphological characteristics were assessed by atomic force microscopy (AFM).Results: At 37 °C, the liposomes and archaeosomes interacted with cell membranes predominantly by fusion and endocytosis. The AFM images showed uniform and dispersed distribution of the liposomes.Conclusion: The findings demonstrate that bacterial liposomes and archaeosomes may be useful as drug delivery carriers for the treatment of cancer.Keywords: Liposome, Archaeosome, E. coli, Acidianus brierleyi, Sulfolobus acidocaldarius, Cancer, HT-29 cell, Atomic force microscopy, Film metho