Formulation Development of Natural Polymeric Nanoparticles, In Vitro Antiaging Evaluation, and Metabolite Profiling of Toona sinensis Leaf Extracts

<b>Background/Objectives:</b> Natural polymer nanoparticles have potential as delivery systems, can enhance pharmacological activity, and can improve stability in the cosmetic field. In this research, we implemented a development approach for chitosan-alginate and chitosan-pectin nanoparticles. This study aimed to investigate effect of formulation, process variables, in vitro antiaging evaluation, and metabolite profiling of <i>Toona sinensis</i> leaf extracts. <b>Methods</b>: Polymeric nanoparticles have been prepared using the ionic gelation method (Temperature = 40 °C, time = 1 h and speed = 1000 rpm), in vitro antiaging evaluation using the Neutrophil Elastase Inhibitor Screening Kit method, and analysis of metabolite profiling with UHPLC-HRMS. <b>Results</b>: Research results found that the SLE and EAFSL nanoparticles that have good and stable characteristics before and after storage in a climatic chamber after 3 months are FIIA-NPSLE (0.75% chitosan and 1.25% Alginate), FIP-NPSLE (1% chitosan and 0.5% Pectin), FIIA-NPEAFSL (0.75% chitosan and 1.25% Alginate), and FIIIP-NPEAFSL (0.125% chitosan and 0.375% Alginate). Chitosan-alginate polymers, such as FIIA-NPEAFSL, have higher inhibition of the elastase enzyme than FIIA-NPSLE, with a % inhibition (IC₅₀) of FIIA-NPEAFSL being 87.30%, while the IC₅₀ of FIIA-NPSLE is 39.40%. Meanwhile, using chitosan-pectin polymers, such as FIP-NPSLE, results in lower inhibition of the elastase enzyme compared to the chitosan-alginate polymer, with an IC₅₀ of 27.28% while IC₅₀ FIIIP-NPEAFSL is 39.53%. SLE and EAFSL nanoparticles with chitosan-alginate and chitosan-pectin polymers resulted in a significant PDI during storage from 1.3 to 1.9, and zeta potential values were very low, ranging from -11 mV to -27 mV. Metabolite profiling using UHPLC-HRMS on <i>T. sinensis</i> leaf extracts revealed that the main compounds contained were glycitein, quercetin, quercetin-3β-D-glucoside, kaempferol, and ellagic acid, which has potential as an antiaging agent. <b>Conclusions</b>: It can be concluded that using chitosan, alginate, and pectin in the process of encapsulating extracts into nanoparticles with the same process variables affect evaluation of antiaging activity in elastase enzymes. Further research will develop these nanoparticles into nanohydrogels with antiaging activity.