Banca de DEFESA: VICTÓRIA LAYSNA DOS ANJOS SANTOS

DEVELOPMENT OF ELECTROSPINTED FIBER CONTAINING FLUORESCENT NAPHTOIMIDAZOLE FOR USE AS 

ANTINEOPLASTIC THERANOSTIC.

Naphthoazoles. Naphthoimidazole. Cancer. Electrospinning. Antineoplastic theranostics.

Cancer has high incidence and mortality rates associated with its occurrence. Currently, antineoplastic chemotherapy and its diagnosis have limitations, and the development of more effective agents is attractive. Among the strategies used is the theranostic approach, characterized by the combination of therapy and diagnostic techniques in a single system. Naphthoazoles are promising candidates to act as theranostic agents, since they have high antineoplastic activity as well as the ability to emit fluorescence. Thus, the development of a pH-dependent fiber produced by electrospinning containing naphthoazole derived from α-lapachone was proposed to be used as an anticancer and fluorescent theranostic agent used after tumor resection. Naphthoazoles were synthesized from the Debus-Radziszewski reaction, using α-lapachone as a structural framework. Four naphthoazoles were obtained, two of which were naphthoimidazoles (IM3 and IM4) and two naphthoxazoles (OX4 and OX5). The naphthoazoles were obtained in yields of 25.4 and 43.9% and their structures were confirmed by Nuclear Magnetic Resonance (NMR) and Mass Spectroscopy (MS). The physicochemical and thermal characterization of the naphthoazoles was performed by infrared (FT-IR), X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC) and Thermogravimetry coupled to Differential Thermal Analysis (DTA) analyses. Tests were also performed to develop the quantification method by HPLC-DAD and solubility tests. The synthesized naphthoazoles were also evaluated for their potential application as components of anticancer nanotheranotics, where it was observed that naphthoimidazole IM4 exhibits greater applicability as a therapeutic component, while naphthoxazoles demonstrated more attractive photophysical properties. Thus, IM4 was used to produce a pH-dependent fiber, produced by electrospinning and employing Eudragit® L100 as polymer. The fiber was obtained with a loading rate of 2.79 ± 0.19% (w/w) of IM4 and was characterized by SEM, FTIR, NMR, thermal TG and DSC analyses, and dissolution tests in two pH ranges (7.4 and 6.8). The tests demonstrated that the fiber was micrometer-sized, with a regular cylindrical shape, characteristic of electrospun Eudragit® L-100, and the IM4 signals were identified by 1H NMR and HPLC, demonstrating the incorporation of IM4 into the fiber. In the fiber dissolution tests, a rapid release was observed between 15 and 20 minutes for pH 6.8 and 7.4 media, respectively. The properties presented by NFIM4, the fiber produced, make it a promising fiber for use as a theranostic after surgical removal of tumors.