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Biomedical subjects

Elka Touitou

Publications and source records attributed to Elka Touitou.

5 recordsLinked to original sources

Treatment of malaria in a mouse model by intranasal drug administration.

The goal of this work was to investigate intranasal dihydroartemisinin (DHA) delivery as a non-invasive method for treatment of malaria. ICR female mice were infected with Plasmodium berghei ANKA, a model for severe malaria with similarities to the human disease. DHA, at a dose of 2 x 5mg/kg/day, was administered to mice either intranasally or i.p. Two dosage regimens were tested: prophylaxis and treatment. Parasitemia was monitored every other day, from the time of infection, by thin smears prepared from tail blood. The survival rates in prophylaxis and treatment regimens were 93% and 75%, respectively, for intranasal DHA and this route was at least as effective as the i.p. route used for comparison. All mice in the untreated control and placebo groups succumbed due to the parasitemia. The results show that DHA nasal administration to mice was highly efficient in the treatment of Plasmodium infection in infected rodents. This novel mode of drug administration may be considered as an alternative to conventional treatment.

Administration, Intranasal↗

Erythromycin ethosomal systems: physicochemical characterization and enhanced antibacterial activity.

The rationale behind this work was that a permeation enhancing carrier could facilitate the transport of antibacterial molecules through the two biological barriers: stratum corneum of the skin and bacterial membrane/cell wall. To this end, erythromycin ethosomes (EE) were designed and characterized, and their antibacterial efficiency was evaluated in vitro and in vivo. TEM, CLSM, DLS, DSC and ultracentrifugation tests indicate that EE are small unilamellar soft vesicles encapsulating 78.6% erythromycin. The compositions were stable for at least one year at room temperature. In live/dead viability/cytotoxicity tests, EE systems were nontoxic to cultured 3T3 dermal fibroblasts. Susceptibility studies conducted on three bacterial strains (B. subtilis ATCC 6633, S. aureus ATCC 29213 and S. aureus clinically resistant to erythromycin) showed significantly larger inhibition zones for EE as compared to erythromycin in hydroethanolic solutions. Moreover, EE reduced erythromycin MIC as compared to control solution: from 2.5 to 1.25 microg/ml for S. aureus ATCC 29213 and from 12.5 to 5.0 microg/ml for clinically isolated resistant S. aureus strain. Ethosomal erythromycin applied to the skin of ICR mice inoculated with 10(7)cfu S. aurues ATCC 29213 resulted in complete inhibition of infection. On the contrary, when hydroethanolic solution of erythromycin was applied, deep dermal and subcutaneous abscesses developed within five days after challenge. On day seven, a similar number of S. aureus colonies (1.06x10(7) vs. 0.90x10(7) cfu/g tissue) were isolated from the untreated wounds or treated with hydroethanolic erythromycin. For these animals, histopathological examination showed necrosis, destroyed skin structures and dense infiltrates of neutrophils and macrophages. These findings show that ethosomes are efficient carriers for erythromycin delivery to bacteria localized within the deep skin strata for eradication of staphylococcal infections.

Animals↗

Ethosomes: new prospects in transdermal delivery.

Ethosomes are noninvasive delivery carriers that enable drugs to reach the deep skin layers and/or the systemic circulation. Although ethosomal systems are conceptually sophisticated, they are characterized by simplicity in their preparation, safety, and efficacy--a combination that can highly expand their application. Ethosomes are soft, malleable vesicles tailored for enhanced delivery of active agents. This article reviews work carried out in vitro, in vivo, in animal models, and in humans with various ethosomal systems incorporating a wide range of drugs. Because of their unique structure, ethosomes are able to encapsulate and deliver through the skin highly lipophilic molecules such as cannabinoids, testosterone, and minoxidil, as well as cationic drugs such as propranolol and trihexyphenidil. Results obtained in a double-blind two-armed randomized clinical study showed that treatment with the ethosomal acyclovir formulation significantly improved all the evaluated parameters. Preliminary studies with plasmids and insulin revealed that the ethosomal carrier may be used for enhanced delivery of these agents. In further work, the ethosomal technology was broadened to introduce agents into cultured cells and microorganisms. Enhanced delivery of bioactive molecules through the skin and cellular membranes by means of an ethosomal carrier opens numerous challenges and opportunities for the research and future development of novel improved therapies.

Administration, Cutaneous↗

Drug delivery across the skin.

For more than two decades, researchers have attempted to find a way to use the skin as a portal of entry for drugs in order to overcome problems associated with traditional modes of drug administration. This has been a complicated task due to the highly effective barrier properties of the skin. In order to deliver drugs through the skin, most compounds require various degrees of permeation enhancement. Classic enhancement methods focused primarily on chemical enhancement or modulation of interactions between the drug and the vehicle. More recent research makes use of innovative vesicular carriers, electrically assisted delivery and various microinvasive methods, some incorporating technologies from other fields. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This review discusses the different types of permeation enhancement, both classic and innovative, and summarises the current strengths and shortcomings in the field with an emphasis on those that have led to products on the market or in the pipeline.

Administration, Cutaneous↗

Testosterone ethosomes for enhanced transdermal delivery.

Physiological decrease in testosterone levels in men with age causes various changes with clinical significance. Recent testosterone replacement therapy is based mainly on transdermal nonpatch delivery systems. These products have the drawback of application on extremely large areas to achieve required hormone blood levels. The objective of the present study was to design and test a testosterone nonpatch formulation using ethosomes for enhanced transdermal absorption. The ethosomal formulation was characterized by transmission electron microscopy and dynamic light scattering for structure and size distribution and by ultracentrifugation for entrapment capacity. To evaluate the feasibility of this delivery system to enhance testosterone permeation through the skin, first the systemic absorption in rats was compared with a currently used gel (AndroGel). Further, theoretical estimation of testosterone blood concentration following ethosomal application in men was made. For this purpose, in vitro permeation experiments through human skin were performed to establish testosterone skin permeation values. In the design of these experiments, testosterone solubility in various solutions was measured and the effect of the receiver medium on the skin barrier function was assessed by confocal laser scanning microscopy. Theoretical estimation shows that testosterone human plasma concentration value in the upper part of the physiological range could be achieved by application of the ethosomal formulation on an area of 40 cm(2). This area is about 10 times smaller than required with current nonpatch formulations. Our work shows that the ethosomal formulation could enhance testosterone systemic absorption and also be used for designing new products that could solve the weaknesses of the current testosterone replacement therapies.

Animals↗