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Yanina Martinez, Speaker at Chemical Engineering Conferences
National Atomic Energy Commission, Argentina
Title : Spectrofluorimetric study of the reversible self-assembly of Irinotecan in aqueous medium

Abstract:

Factors like concentration, pH, or ionic strength induce self-aggregation in some drugs.

It is important to study the self-assembly of drugs to relate the structure with their biological function. In this oral presentation I will share with you some experimental research related to the effect of decreasing Irinotecan commercial injectable solution concentration in the fluorescence intensity to study the aggregation behavior solely in an aqueous environment. Irinotecan intrinsic fluorescence emission was useful to track the emission variation along the different concentrations. In this sense, stock solution (34 mM) was serial diluted in physiological solution and as the concentration decreased from 34 mM to 0.85 μM of Irinotecan, the fluorescence intensity increased suggesting that the fluorescence emission was quenched at high concentrations. The spectrofluorimetric technique chosen for the present work was accurate to infer a possible change in the spatial conformation of the molecule because a blue shift with respect to the monomer of the maxima wavelength at

0.85 μM was observed and might be associated with H-aggregated forms, H stands for hypsochromic blue shifted emission bands. At 34 mM (2 mg/mL) a red shift of the maxima wavelength was associated with J-aggregates (J for bathochromic shift).

The disaggregation was only possible under serial dilutions and was not avoided in the presence of Bovine Serum Albumin (BSA) which is the most abundant soluble protein in the

 

bloodstream of mammals and is responsible for the transport of many molecules such as ligands that bind to their receptors. It is important to study the binding of drugs to BSA for because a high affinity ensures a high drug biodistribution.

 

The aggregates were characterized by scanning electron microscopy (SEM) and colloidal shapes of 5-7 micrometer were observed .Energy Dispersive X-ray Spectrometry EDS reports of the distribution of the elements confirmed C, O and N asigned to Irinotecan molecule. Furthermore confocal microscopy studies showed crystal structures of 5 μm size not reported before. Nowadays, the therapeutic dose of Irinotecan for cancer treatment range from 0.12 to 2.8 mg/mL so according to these results, the drug is administered as a self- assembled structure immersed in an aqueous solution or as a colloid.

Further experiments should be conducted to relate the self-assembled structure with the biological function.

Biography:

Dr. Martinez is a bachelor of Biotechnology, (National University of Quilmes) Buenos Aires, Argentine. She is a Dr. in Biological Sciences (National University of La Plata) Argentine. At present, her research area at the National Atomic Energy Commission focuses on the development of simple and double emulsions for health applications using non-ionic polymeric surfactants for controlled release studies. Besides, her interests reside in the study of the effect of the self-aggregation of therapeutic molecules on the kinetics release and the relationship of the structure with the biological function.

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