Stabilization of Distearoylphosphatidylcholine Lamellar Phases in Propylene Glycol Using Cholesterol

Abstract

Phospholipid vesicles (liposomes) formed in pharmaceutically acceptable nonaqueous polar solvents such as propylene glycol are of interest in drug delivery because of their ability to improve the bioavailability of drugs with poor aqueous solubility. We have demonstrated a stabilizing effect of cholesterol on lamellar phases formed by dispersion of distearoylphosphatidylcholine (DSPC) in water/propylene glycol (PG) solutions with glycol concentrations ranging from 0 to 100%. The stability of the dispersions was assessed by determining the effect of propylene glycol concentration on structural parameters of the lamellar phases using a complementary combination of X-ray and neutron scattering techniques at 25 °C and in the case of X-ray scattering at 65 °C. Significantly, although stable lamellar phases (and liposomes) were formed in all PG solutions at 25 °C, the association of the glycol with the liposomes' lamellar structures led to the formation of interdigitated phases, which were not thermostable at 65 °C. With the addition of equimolar quantities of cholesterol to the dispersions of DSPC, stable lamellar dispersions (and indeed liposomes) were formed in all propylene glycol solutions at 25 °C, with the significant lateral phase separation of the bilayer components only detectable in propylene glycol concentrations above 60% (w/w). We propose that the stability of lamellar phases of the cholesterol-containing liposomes formed in propylene glycol concentrations of up to 60% (w/w) represent potentially very valuable drug delivery vehicles for a variety of routes of administration.

Phospholipid Vesicle-Based Permeation Assay and EpiSkin® in Assessment of Drug Therapies Destined for Skin Administration

“…PVPA c with cholesterol incorporated into the liposomes thus exhibited a drastic increase in storage stability compared to PVPA o , which contained only E‐80 in the barriers. Cholesterol is known to have a stabilizing effect on liposomes, and its incorporation into liposomes for PVPA c barriers resulted in consistent and reproducible permeability results for calcein following storage for up to 16 months.…”

Lawsone-loaded Niosome and its antitumor activity in MCF-7 breast Cancer cell line: a Nano-herbal treatment for Cancer

“…High encapsulating efficiently of Lawsone in niosomes is because of hydrophobic nature of Lawsone that results in more affinity and tus more incorporation in niosomes bilayers. Law interacts with the acyl chains of niosome bilayers and can stabilize the formulation [49].…”

On the structure of an aqueous propylene glycol solution

“…In the pharmaceutical industry, propylene glycol is used as a solvent to increase the apparent solubility and the permeation of drugs through lipid membranes [16][17][18][19][20] and as such is used commonly as a co-solvent in oral, intravenous [21][22][23] and topical preparations. 18,24 Interestingly, encapsulating drugs into PG containing liposomes results in a substantial increase in drug-solubility which increases with PG concentration.…”

“…25 The addition of PG to distearoylphosphatidylcholine containing lamellar phases results in an decrease in lamellar thickness and with increasing PG concentrations. 21,26 Furthermore, computational studies have suggested that PG induces pore formation in DOPC bilayers at concentrations ≥ 15 mol%. 27 Despite its importance in a range of industrial applications, limited structural information exists for propylene glycol, in comparison to ethylene glycol.…”