Chitosan Nanoparticles Entrapping Aqueous Psidium guajava L. Leaf Extracts: A Promising Approach for Topically Treating Disorders in Oral Mucosa

<i>Psidium guajava</i> L. (Myrtaceae) is a neotropical species whose leaf extracts demonstrate efficacy against cutaneous and mucosal inflammation and ulceration. This study aimed to prepare and characterize aqueous extracts of <i>P. guajava</i> leaves (EAPG) and incorporate them into chitosan nanoparticles for topical delivery to the oral mucosa. The extract was obtained by infusion, and its marker compound was quantified by a chromatographic method. EAPG exhibited antioxidant activity (IC₅₀: 6.35-7.01 µg/mL in DPPH^•; FRAP: 14.42-17.83 µg/mL ≈ 60 µM Fe²⁺) and anti-inflammatory potential by modulating the expression of IL-6. It also showed antifungal activity against <i>Candida</i> species. Nanoparticles loaded with EAPG had a mean diameter of 899.8 ± 10.8 nm, PdI 0.22 ± 0.03, Zeta potential +32.4 ± 2.3 mV, pH 5.0, and 62 ± 1% encapsulation efficiency. They remained stable for 30 days. In an ex vivo topical application, EAPG nanoparticles delivered 415.17 ± 71.7 µg/cm² of marker to the oral mucosa, eight times more than free EAPG (<i>p</i> < 0.05). These results suggest that chitosan-based EAPG nanoparticles are a promising strategy for topical treatment of mucosal disorders.