Red Prickly Pear (Opuntia ficus-indica) Pulp Fruit Phenolic Extract Encapsulated in a Chitosan–Maltodextrin Liposomal Delivery System: Biological Evaluation and Functional Characteristics in Yogurt

Red prickly pear (Opuntia ficus-indica) fruit as a potential source of phenolic compounds with biological and functional-food applications was investigated. The present study aimed at the detailed characterization of red prickly pear pulp fruit phenolic extract (RPPP-PE), determination of its antimicrobial and anti-hepatitis A virus (HAV) activities, elucidation of the molecular interactions of the identified phytochemicals with HAV 3C protease using docking and ADME analyses, and development of a liposomal formulation associated with chitosan–maltodextrin for yogurt fortification. RPPP-PE was obtained by ultrasound-assisted ethanol–water extraction and analyzed by HPLC-DAD. The most abundant phenolics were epicatechin and catechin (148.40 and 137.58 µg/g, respectively). The RPPP-PE showed antimicrobial activity against several tested microorganisms and anti-HAV activity in Vero cells (IC50 = 59.42 ± 2.34 μg/mL; SI = 3.98). Docking of 15 identified phytochemicals against two HAV 3C protease structures (2CXV and 2HAL) revealed rosmarinic acid, apigenin-7-glucoside, and epicatechin gallate as favorable binders. ADME analysis showed an affinity–permeability trade-off for the leading candidates. RPPP-PE was then loaded into lecithin liposomes complexed with chitosan and maltodextrin. The chosen formulation, PEL-0.50-CS/MD, had a particle size of 199.0 nm, a zeta potential of −30.47 mV, and an encapsulation efficiency of 86.46%. Adding PEL-0.50-CS/MD significantly increased phenolic content and antioxidant capacity and improved syneresis during refrigerated storage. The 5% supplementation level showed starter culture viability closest to the control. However, higher inclusion levels declined more sharply over time. These results confirm the biological relevance of RPPP-PE and its use in a chitosan–maltodextrin-associated liposomal system for functional yogurt development.