Preparation and Characterization of PEG-PLA Genistein Micelles Using a Modified Emulsion-Evaporation Method

Abstract

The objective of this study is to improve the bioavailability of genistein by encapsulation with polyethylene glycol-polylactic acid (PEG-PLA) copolymers. Genistein micelles (GMs) prepared using a modified emulsion-evaporation method were more stable than those made with the original method. The effect of polyvinyl alcohol, Tween 80, sonication time, PEG-PLA/genistein ratio, and organic phase (acetone)/H2O ratio on the size, polydispersity index, encapsulation efficiency, and drug loading efficiency of GMs was investigated. GMs were obtained and characterized under optimal experimental conditions. For long-term storage, GMs were lyophilized by freeze drying with trehalose to produce genistein lyophilized powder (GLP). The analysis of GLP by Fourier-transform infrared spectroscopy and differential scanning calorimetry showed that genistein was successfully incorporated into the micellar structure. In vitro release experiments revealed that the incorporation of genistein into PEG-PLA copolymers significantly improved its solubility and bioavailability. GLP was more potent in inhibiting the proliferation of HSC-T6 cells than genistein. Treatment with GLP at 10–20 μg/mL for 48 h significantly inhibited the protein expression of α-smooth muscle actin and collagen I in HSC-T6 cells compared with the control. These data demonstrated that the improved solubility and bioavailability of genistein in the form of GLP enhanced its antifibrotic effect in vitro.

Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment

“…The saturated solubility of GS was found to be 2.09 µg/mL which is agreed with the reported value (2.03 µg/mL) [8]. The order of solubility found as follows GS TC > GS-BC > GS-TM > GS-BM > GS, as depicted in Figure 3.…”

“…The aliquot was filtered through a membrane filter and the GS concentration analyzed by the HPLC method [26]. The release data of GS TC was fitted to different release kinetic models to select the best fit model [8].…”

“…It is used as a nutraceutical ingredient in food as well as in the pharmaceutical industry. Furthermore, it exhibited reduced bioavailability due to its limited solubility (1.43 µ g/mL) [8], first-pass metabolism by glucuronidation and sulfation [9]. Many strategies have been applied to overcome the problem associated with GS, including nanoparticles [10][11][12], cyclodextrin complex [13], amylose complexes [14], Zein NPs [15], Zein/Carboxymethyl cellulose-chitosan coated NPs [10], micelles [8], NLCs [9], and eudragit-NPs [16].…”

“…Furthermore, it exhibited reduced bioavailability due to its limited solubility (1.43 µ g/mL) [8], first-pass metabolism by glucuronidation and sulfation [9]. Many strategies have been applied to overcome the problem associated with GS, including nanoparticles [10][11][12], cyclodextrin complex [13], amylose complexes [14], Zein NPs [15], Zein/Carboxymethyl cellulose-chitosan coated NPs [10], micelles [8], NLCs [9], and eudragit-NPs [16]. Hydroxypropyl β cyclodextrin (HP-β-CD) is a cyclic oligosaccharide compound and it is obtained from the β-cyclodextrin by incorporation of hydroxyl propyl group on reaction with propylene oxide [17].…”

Poly(chitosan-ester-ether-urethane) Hydrogels as Highly Controlled Genistein Release Systems

“…GEN concentration in the in vitro samples was also determined by HPLC (detected at the wavelength of 262 nm). The mobile phase was composed of 70% methanol and 30% water with 0.1% phosphoric acid [62,63]. The release data points were subjected to zero-order, first-order kinetics and Korsmeyer-Peppas models, respectively.…”