Zein nanoparticles with bioadhesive potential for oral administration of propranolol: in vitro, in vivo and ex vivo investigations

Oral administration is a common route for medications but faces challenges such as pH variations and enzymatic activity in the gastrointestinal tract. Zein nanoparticles, a biocompatible plant-based protein, emerge as a promising solution to overcome these barriers and enhance the bioavailability of drugs such as propranolol, a beta-blocker with low solubility and bioavailability. This study evaluated the safety of zein nanoparticles for the oral delivery of propranolol through hemocompatibility, cytotoxicity, and ecotoxicity tests, as well as their mucoadhesive efficacy in porcine small intestine. The hemocompatibility test showed that both propranolol-loaded nanoparticles (NZ-PROP) and drug-free nanoparticles (NZ-EMP) did not cause damage to red blood cells, with results comparable to the negative control (0.9% saline). In cytotoxicity assays using the Caco-2 cell line (human colorectal epithelial adenocarcinoma), both the nanoparticles and free propranolol demonstrated 100% cell viability across all tested concentrations (15.625 to 250 μg·mL -1 ). In ecotoxicity tests using Artemia salina , free propranolol caused 100% mortality of nauplii at concentrations of 62.5, 250, and 500 μg·mL -1 , whereas the nanoparticles showed viability at all tested concentrations,indicating reduced toxicity. The mucoadhesive strength of the nanoparticles in porcine small intestine was higher than that of free propranolol, with a maximum detachment force of 0.2585 ± 0.05 N·cm -2 and an adhesion work of 0.0381 ± 0.002 mN×m, supporting prolonged drug release. These findings suggest that zein nanoparticles are safe and effective for the oral delivery of drugs with low permeability.