Casimiroa edulis Leaf Extract–Loaded PLGA Nanoparticles: Untargeted Phytochemical Profiling and Wound-Healing-Oriented Antioxidant/Occlusive Characterization

<b>Background:</b> Nanoparticles are a promise for wound-healing therapies. However, its lack of efficacy/safety represents a real challenge for therapeutic use. <b>Objectives:</b> To overcome these problems, the ethanolic extract of <i>Casimiroa edulis</i> leaves, previously reported for its anti-inflammatory, antibiotic, and antioxidant activities, was characterized by FIA-ESI-FTICR-MS and encapsulated in biodegradable nanoparticles for potential wound-healing therapies. <b>Methods:</b><i>Casimiroa edulis</i>-loaded nanoparticles (CE-NP) were prepared using the rapid emulsion-diffusion method and characterized by their particle size distribution, molecular interactions, charge, morphology, pH, physical stability, and antioxidant and occlusive effects. <b>Results:</b> A total of 40/34 ions in positive/negative electrospray ionization modes were obtained from the extract exploration analysis and were putatively annotated by accurate mass against databases with an error tolerance ≤10 mDa. The most abundant compounds showed the following order: tetramethylscutellarein > rutin > S-usnate > lactose > eugenol derivative > rotenone. While polyphenols predominated, carbohydrates, depsidones/other phenolics, etc., were also detected. The solid/spherical nanoparticles observed by TEM were obtained with a blend of acetone:methyl ethyl ketone (75:25) as the organic phase, producing a unimodal particle size (169.30 ± 1.30 nm; PdI = 0.08 ± 0.03). The encapsulation/loading percentages were 57 ± 0.74/1.62 ± 0.02%, ensuring an entrapment of half the extract, as observed in the FTIR studies. The light backscatter profiles show minimal differences, indicating physical stability correlated with the Z potential (-9.45 ± 1.73 mV). The antioxidant activity of the extract/nanoparticles at 40 µg/mL was 17.27 ± 2.86/16.73 ± 1.28 μg/mL, two-fold higher than that previously reported for sapote seeds. <b>Conclusions:</b> Biodegradable CE-NP with suitable characteristics were obtained for the first time, representing a preliminary proposal for wound healing. Efficacy studies are required.