Tatiana Tozar

Toxicity study in blood and tumor cells of laser produced medicines for application in fabrics.

Phenothiazine derivatives are non-antibiotics with antimicrobial, fungistatic and fungicidal effects. We exposed to a high energy UV laser beam phenothiazines solutions in water at 20mg/mL concentration to increase antibacterial activity of resulting mixtures. Compared to previous results obtained on bacteria, more research is needed about UV laser irradiated phenothiazines applications on cancer cell cultures to evidence possible anticancerous properties. Evaluation of the safety of the newly obtained photoproducts in view of use on humans is also needed. Due to expensive animal testing in toxicology and pressure from general public and governments to develop alternatives to in vivo testing, in vitro cell-based models are attractive for preliminary testing of new materials. Cytotoxicity screening reported here shows that laser irradiated (4h exposure time length) chlorpromazine and promazine are more efficient against some cell cultures. Interaction of laser irradiated phenothiazines with fabrics show that promethazine and chlorpromazine have improved wetting properties. Correlation of these two groups of properties shows that chlorpromazine appears to be more recommended for applications on tissues using fabrics as transport vectors. The reported results concern stability study of phenothiazines water solutions to know the time limits within which they are stable and may be used.

Chlorpromazine transformation by exposure to ultraviolet laser beams in droplet and bulk.

Multiple drug resistance requires a flexible approach to find medicines able to overcome it. One method could be the exposure of existing medicines to ultraviolet laser beams to generate photoproducts that are efficient against bacteria and/or malignant tumors. This can be done in droplets or bulk volumes. In the present work are reported results about the interaction of 266nm and 355nm pulsed laser radiation with microdroplets and bulk containing solutions of 10mg/ml Chlorpromazine Hydrochloride (CPZ) in ultrapure water. The irradiation effects on CPZ solution at larger time intervals (more than 30min) are similar in terms of generated photoproducts if the two ultraviolet wavelengths are utilized. The understanding of the CPZ parent compound transformation may be better evidenced, as shown in this paper, if studies at shorter than 30minute exposure times are made coupled with properly chosen volumes to irradiate. We show that at exposure to a 355nm laser beam faster molecular modifications of CPZ in ultrapure water solution are produced than at irradiation with 266nm, for both microdroplet and bulk volume samples. These effects are evidenced by thin layer chromatography technique and laser induced fluorescence measurements.

Laser Optofluidics in Fighting Multiple Drug Resistance

The interaction of laser modified medicine solutions with hydrophilic and hydrophobic target surfaces has been investigated under the effect of simulated hypergravity conditions, employing the Large Diameter Centrifuge (LDC) facility, developed by the European Space Agency (ESA). Experiments have been performed within the HyperMed project under the aegis of the ESA “Spin Your Thesis!” 2015 programme. During centrifugation, real-time video files have been recorded regarding generation of ultrapure water, unexposed and laser exposed chlorpromazine aqueous pendant droplets, followed by their detachment due to the exerted high gravitational accelerations and finally by the formation of sessile droplets on target surfaces. In this way, information about the volume of the generated droplet, the degree of wetting and its time evolution at different hypergravity levels has been obtained. Phenothiazine solutions irradiated with UV laser radiation indicate reduced surface tension, thus presenting better wetting properties. Target surfaces impregnated with medicine solutions may constitute an unconventional tool and even vector in developing new drug delivery systems. Such a wetting process under high g-level conditions may be useful in space medicine applications. Microorganisms can survive, grow and even proliferate under the effect of increased gravity. Therefore, upon launching of a spacecraft, during a long-term mission in microgravity conditions, astronauts and spacecraft surfaces may require treatment and decontamination, respectively, against onboard infectious microbes. Since non-terrestrial gravity may alter drug properties, medicine droplets behaviour in interaction with target surfaces under hypergravity conditions is the aim of the present study.

Stability studies on Promethazine unexposed and exposed to UV laser radiation

As a phenothiazine derivative, Promethazine may undergo structural modifications when it is exposed to light. This process consists in the degradation of the initial compound and in the generation of new photoproducts with possible anti-infectious qualities. Stability studies are necessary in order to establish the proper use of drug solutions in different applications. At the same time, these investigations are important in the context of the generation of side-products induced by environmental conditions that bring new benefits to the compound. This study reports the stability of Promethazine aqueous solutions, based on their absorption spectra acquired before and after Nd:YAG laser irradiation sessions or under different temperature and illuminating storage conditions. Samples of Promethazine solutions in ultrapure water, at a concentration range between 10-6 M – 10-2 M, were kept in dark at 22°C, and 4°C as well as at 22°C in ambient light up to a time interval of three months. Absorption spectra were recorded periodically in order to determine any changes of the optical properties. Also, solutions of 20 mg/mL were exposed for different time intervals to laser radiation emitted at 266 nm by the Nd:YAG laser. The stability of the optical properties of irradiated Promethazine solutions for 4 h was investigated up to two months. The laser irradiated samples show similar but more rapid and intense changes compared to solutions exposed to ambient light, suggesting molecular modifications that could be due to the production of more polar phenothiazine derivatives.