Phosphatidylinositol Stabilizes Fluid-Phase Liposomes Loaded with a Melphalan Lipophilic Prodrug

Abstract

Previously, a liposomal formulation of a chemotherapeutic agent melphalan (Mlph) incorporated in a fluid lipid bilayer of natural phospholipids in the form of dioleoylglyceride ester (MlphDG) was developed and the antitumor effect was confirmed in mouse models. The formulation composed of egg phosphatidylcholine (ePC), soybean phosphatidylinositol (PI), and MlphDG (8:1:1, by mol) showed stability in human serum for at least 4–5 h. On the contrary, replacing PI with pegylation of the liposomes, promoted fast dissociation of the components from the bilayer. In this work, interactions of MlphDG-liposomes with the most abundant plasma protein—albumin—in function of the presence of PI in the formulation were explored using Fourier transform infrared spectroscopy. The release of MlphDG from the liposomes was studied by asymmetrical flow field-flow fractionation (AF4) using micelles formed by a polyethylene glycol conjugate with phosphatidylethanolamine to mimic the physiological lipid sink like lipoproteins. Our results show that PI actually protects the membrane of MlphDG-liposomes from the protein penetration, presumably due to pairing between the positively charged MlphDG and negatively charged PI, which compensates for the heterogeneity of the lipid bilayer. The AF4 technique also evidences high stability of the formulation as a drug carrier.

The Influence of Lipid Matrix Composition on the Microenvironment of Levofloxacin in Liposomal Forms

“…A change in the position of absorption bands and their shape indicates a change in the microenvironment of the corresponding functional groups. Hence, the analysis of IR spectra makes it possible to identify the main binding sites of ligands including small organic molecules [ 15 ].…”

Cholesterol Significantly Affects the Interactions between Pirfenidone and DPPC Liposomes: Spectroscopic Studies

“…The analytically significant νPO 2 − as band is of greatest interest as it is sensitive to the interaction of cationic ligands with the polar head of liposomes. A change in the position of absorption bands and their shape indicates a change in the microenvironment of the corresponding functional groups; thus, the analysis of ATR-FTIR spectra makes it possible to identify the main binding sites of ligands including small organic molecules [29]. When the liposomal membrane interacts with pirfenidone, the following regularities are observed.…”

Selenylated indoles: synthesis, effects on lipid membrane properties and DNA cleavage

“…Only the 3a increased the wavenumber of ASO v s PO 2 − (from 1082.07 cm −1 to 1093.64 cm −1 , a variation equivalent to 11.57 cm −1 ), which suggest that this selenylated indole discreetly reduces the hydration degree of the phosphate group. 18 a ,22 Here, it is possible that an anion–π interaction between the anionic ASO phosphate ester with the electron-deficient 3a phenyl substituent and/or hydrogen bonds formed between the lipid phosphate and the indoleamine have competed with the formation of hydrogen bonds between the phosphate and water molecules. 23 The other selenylated indoles decreased the ASO v s PO 2 − wavenumber, and, consequently, increased the hydration degree of the lipid phosphate, in the order 3c (promoting a v s PO 2 − wavenumber decrease by 11.58 cm −1 ) > 3b (wavenumber decrease by 7.72 cm −1 ) > 3d (wavenumber decrease by 3.86 cm −1 ).…”