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

Psidium guajava 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 P. guajava 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 Candida 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 (p < 0.05). These results suggest that chitosan-based EAPG nanoparticles are a promising strategy for topical treatment of mucosal disorders.