Oral Delivery of Avocado Peel Extract Using Albumin Nanocarriers to Modulate Cholesterol Absorption

<b>Background/Objectives:</b> Hypercholesterolemia, a metabolic disorder and major risk factor for cardiovascular disease, remains a global health concern. Although current pharmacological interventions effectively reduce cholesterol levels, their use is often associated with adverse side effects. These limitations have driven interest in alternative or complementary approaches based on natural products; however, the poor solubility, stability, and bioavailability of many natural compounds emphasize the need for innovative drug delivery systems to enhance their health-promoting potential. The extract obtained from <i>Persea americana</i> peels, a sustainable and underutilized by-product, has previously been reported to have cholesterol-lowering properties. <b>Methods</b>: The extract was encapsulated in bovine serum albumin nanoparticles. The nanoformulation was characterized for physicochemical properties and for extract stability under acid-simulated gastric digestion. Safety and biocompatibility were evaluated by in vitro cytotoxicity assays using intestinal Caco-2 and liver HepG2 cells, and in vivo toxicity using <i>Artemia salina</i>. The bioavailability of the extract and the nanoformulation's capacity to reduce cholesterol absorption in a differentiated Caco-2 cell model were additionally assessed. <b>Results</b>: Encapsulation enhanced extract stability and bioavailability, protecting it from degradation in acid simulated gastric digestion. The nanoparticles showed favorable physicochemical properties, including a small size of less than 100 nm, and demonstrated safety and biocompatibility. In the Caco-2 model, the encapsulation of the extract resulted in reduced cholesterol permeation compared to the free extract <b>Conclusions:</b> These findings suggest that the nanoformulation developed may offer a safe and effective strategy for the oral delivery of <i>P. americana</i> peel extract, reinforcing its potential for application in hypercholesterolemia management.