Chitosan–tripolyphosphate nanoparticles as Arrabidaea chica standardized extract carrier: synthesis, characterization, biocompatibility, and antiulcerogenic activity

Abstract

Leila Servat-Medina,1,2 Alvaro González-Gómez,2,3 Felisa Reyes-Ortega,2 Ilza Maria Oliveira Sousa,1 Nubia de Cássia Almeida Queiroz,1 Patricia Maria Wiziack Zago,1 Michelle Pedrosa Jorge,1 Karin Maia Monteiro,1,4 João Ernesto de Carvalho,1 Julio San Román,2,3 Mary Ann Foglio1 1Chemical, Biological and Agricultural Pluridisciplinary Research Center-State University of Campinas (CPQBA-UNICAMP), Campinas-SP, Brazil; 2Biomaterials Group, Polymer Science and Technology Institute-Spanish National Research Council (ICTP-CSIC), 3CIBER-BBN, Centro de Investigación Biomédica en Red, Madrid, Spain; 4Department of Medical Clinics, Faculty of Medical Sciences, University of Campinas, Campinas-SP, Brazil Abstract: Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan–sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract’s composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential candidate for ulcer-healing pharmaceutical systems. Keywords: natural product, Arrabidaea chica, chitosan, nanoparticle, plant extract, herbal drug, ulcer healing