Enhanced Solubility and Bioavailability of Naringenin via Liposomal Nanoformulation: Preparation and In Vitro and In Vivo Evaluations

Abstract

This study was aimed at preparing orally administered naringenin-loaded liposome for pharmacokinetic and tissue distribution studies in animal models. The liposomal system, consisting of phospholipid, cholesterol, sodium cholate, and isopropyl myristate, was prepared using the thin-film hydration method. Physicochemical characterization of naringenin-loaded liposome such as particle size, zeta potential, and encapsulation efficiency produced 70.53 ± 1.71 nm, -37.4 ± 7.3 mV, and 72.2 ± 0.8%, respectively. The in vitro release profile of naringenin from the formulation in three different media (HCl solution, pH 1.2; acetate buffer solution, pH 4.5; phosphate buffer solution, pH 6.8) was significantly higher than the free drug. The in vivo studies also revealed an increase in AUC of the naringenin-loaded liposome from 16648.48 to 223754.0 ng·mL h as compared with the free naringenin. Thus, approximately 13.44-fold increase in relative bioavailability was observed in mice after oral administration. The tissue distribution further showed that the formulation was very predominant in the liver. These findings therefore indicated that the liposomal formulation significantly improved the solubility and oral bioavailability of naringenin, thus leading to wider clinical applications.

Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies

“…Zhang et al [94] aimed to improve the oral absorption of baicalin, which has low solubility and poor permeability, by using a micellar formulation comprised of the carriers Pluronic P123 copolymer and sodium taurocholate. Sustained release profile of baicalin-loaded mixed micelles, in in vitro drug release experiment, held in several pH conditions, showed 14% drug released after 2 h in gastric conditions and 54% release within 48 h in intestinal conditions, compared to 34% and 79% release [105], nanoparticles [106][107][108][109][110], phytosome [111], nanoliposome [112], mixed micelles [113,114], SNEDDS [115,116], nanocarrier [117,118], nanoemulsion [119], nanosuspension [ Mixed micelles [129,130], nanoparticles [131,132], solid dispersion [133,134] , SNEDDS [135] , SMEDDS [136], lipid carrier [137], copolymeric micelles [138], exosomes [139] Naringenin DENV, HCV SNEDDS [140], solid dispersion [141], nanoparticles [142,143] , liposome [144], nanosuspension [145,146] In vitro uptake studies, carried out with a caco-2 cell line, determined the absorption of baicalin within the mixed micelles and verified their internalization ability. Baicalin-loaded ST-P123-MMs formulation achieved high oral bioavailability (Fig.…”

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

“…Naringenin-loaded soluthin-maltodextrin nanocarrier was found to enhance oral bioavailability (116 fold) and to reduce toxicity (21 fold) of naringenin compared to free naringenin [217]. Naringenin-loaded liposomal nanoformulation has been found to increase solubility and oral bioavailability (13.44 fold) of naringenin, thus improving its clinical applications [218]. Despite several nanoformulations of naringenin have been claimed to improve oral bioavailability and therapeutic efficacy against different diseases; however, their potential role in diabetes management is still limited [219].…”

Sunscreen creams containing naringenin nanoparticles: Formulation development and in vitro and in vivo evaluations

“…Incorporation of bio‐actives in nanocarriers promotes permeation across the biological membranes, increases drug loading, and offers the prospect of sustained release and targeted delivery. Naringenin‐loaded nanocarriers such as nanoparticles, solid lipid nanoparticles, and liposomes have been prepared previously to enhance oral bio‐availability of naringenin. However, these studies were restricted to the hepatoprotective effects of naringenin.…”