A novel drug–phospholipid complex enriched with micelles: preparation and evaluation in vitro and in vivo

Abstract

Mixed micelles are widely used to increase solubility and bioavailability of poorly soluble drugs. One promising antitumor drug candidate is 20(S)-protopanaxadiol (PPD), although its clinical application is limited by low water solubility and poor bioavailability after oral administration. In this study, we developed mixed micelles consisting of PPD-phospholipid complexes and Labrasol ® and evaluated their potential for oral PPD absorption. Micelles were prepared using a solvent-evaporation method, and their physicochemical properties, including particle size, zeta potential, morphology, crystal type, drug loading, drug entrapment efficiency, and solubility, were characterized. Furthermore, in vitro release was investigated using the dialysis method, and transport and bioavailability of the mixed micelles were investigated through a Caco-2 cell monolayer and in vivo absorption studies performed in rats.Compared with the solubility of free PPD (3 µg/mL), the solubility of PPD in the prepared mixed micelles was 192.41 ± 1.13 µg/mL in water at room temperature. The in vitro release profiles showed a significant difference between the more rapid release of free PPD and the slower and more sustained release of the mixed micelles. At the end of a 4-hour transport study using Caco-2 cells, the apical-to-basolateral apparent permeability coefficients (P app ) increased from (1.12 ± 0.21) × 10 6 cm/s to (1.78 ± 0.16) × 10 6 cm/s, while the basolateral-to-apical P app decreased from (2.42 ± 0.16) × 10 6 cm/s to (2.12 ± 0.32) × 10 6 . In this pharmacokinetic study, compared with the bioavailability of free PPD (area under the curve [AUC] 0-∞ ), the bioavailability of PPD from the micelles (AUC 0-∞ ) increased by approximately 216.36%. These results suggest that novel mixed micelles can significantly increase solubility, enhance absorption, and improve bioavailability. Thus, these prepared micelles might be potential carriers for oral PPD delivery in antitumor therapies.

Preparation and Evaluation of Phospholipid-Based Complex of Standardized Centella Extract (SCE) for the Enhanced Delivery of Phytoconstituents

“…The prepared SCE-Phospholipon® 90H complex (CN), however, showed a dramatic, and a significant (over 12-fold) increase in the aqueous solubility. This increase in the solubility of the prepared complex may be explained by the partial amorphization (reduced molecular crystallinity) of the drug, and the overall amphiphilic nature of the naturosome (32,51).…”

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

“…Other stellar merits of phospholipidic formulations include ease of preparation, along with high drug loading capacity and long-term stability. Several, literature reports suggest that incorporation of drug-phospholipid complexes into the nanostructured systems can further have remarkable increase in the biopharmaceutical performance of the drugs Rawat et al, 2013;Xia et al, 2013).…”

A nanoparticulate drug-delivery system for 20(S)-protopanaxadiol: formulation, characterization, increased oral bioavailability and anti-tumor efficacy

“…As such, some studies employed cubic nanoparticles (Jin et al, 2013a), lipid cubic nanoparticles (Jin et al, 2013b), drug-phospholipid complex nanoparticles (Xia et al, 2013) and liquid crystalline nanoparticles (Jin et al, 2013c) to resolve this problem, with the bioavailability increased by 69%, 66%, 116%, and 148%, in comparison to the raw PPD material; however, the drug payload of them is less than 20%.…”