RESUMO
Ursolic acid (UA) is a naturally occurring triterpene that has been investigated for its antitumor activity. However, its lipophilic character hinders its oral bioavailability, and therapeutic application. To overcome these limitations, chitosan (CS) modified poly (lactic acid) (PLA) nanoparticles containing UA were developed, characterized, and had their oral bioavailability assessed. The nanoparticles were prepared by emulsion-solvent evaporation technique and presented a mean diameter of 330 nm, zeta potential of +28 mV, spherical shape and 90% encapsulation efficiency. The analysis of XRD and DSC demonstrated that the nanoencapsulation process induced to UA amorphization. The in vitro release assay demonstrated that 53% of UA was released by diffusion after 144 h, following a second-order release kinetics. In simulated gastrointestinal fluids and mucin interaction tests, CS played an important role in stability and mucoadhesiveness improvement of PLA nanoparticles, respectively. In the presence of erythrocytes, nanoparticles proved their hemocompatibility. In tumor cells, nanoparticles presented lower cytotoxicity than free UA, due to slow UA release. After a single oral dose in rats, CS modified PLA nanoparticles increased the UA absorption, reduced its clearance and elimination, resulting in increased bioavailability. The results show the potential application of these nanoparticles for UA oral delivery for cancer therapy.
Assuntos
Quitosana/química , Nanopartículas/química , Poliésteres/química , Triterpenos/química , Triterpenos/metabolismo , Animais , Disponibilidade Biológica , Linhagem Celular Tumoral , Emulsões/química , Eritrócitos/efeitos dos fármacos , Humanos , Masculino , Ratos , Ratos Wistar , Solventes/química , Ácido UrsólicoRESUMO
In this study, we developed, characterized and evaluated the antioxidant activity of poly (lactic acid) nanoparticles containing diphenyl diselenide (PhSe)2. Nanoparticles were characterized in terms of mean particle size, polydispersity index, zeta potential, encapsulation efficiency, in vitro release profile, physical stability, polymer-drug interactions and thermal properties. Also, the antioxidant activity of nanoparticles on hypochlorous acid (HOCl) was assessed. Nanoparticles presented a mean size of 210nm, had low polydispersity, zeta potential of -24mV, and an encapsulation efficiency over 90%. Differential scanning calorimetry and X-ray diffraction results showed (PhSe)2 is dispersed in PLA matrix in an amorphous state. Lyophilized nanoparticles maintained physical stability over three months, while nanoparticles dispersed in water did not present stability over 7days. In vitro release assay was characterized by a biphasic release pattern with burst effect in 8h followed by a sustained release diffusion governed over 192h. Nanoencapsulation did not alter the antioxidant activity of (PhSe)2 on HOCl. The study concludes these properties of (PhSe)2-loaded nanoparticles can be useful to extend the biological effects of (PhSe)2.