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

Abstract

In this work, we studied the effect of as on the interaction of membrane DPPC with the key antifibrotic drug pirfenidone. Liposomal forms of pirfenidone were obtained using passive loading. The addition of cholesterol reduces the loading efficiency of pirfenidone by 10%. The main binding site of pirfenidone in DPPC liposomes is the carbonyl group: the interaction with PF significantly increases the proportion of low-hydrated carbonyl groups as revealed by ATR-FTIR spectroscopy. The phosphate group acts as an additional binding site; however, due to shielding by the choline group, this interaction is weak. The hydrophobic part of the bilayer is not involved in PF binding at room temperature. Cholesterol changes the way of interaction between carbonyl groups and pirfenidone probably because of the formation of two subpopulations of DPPC and causes a dramatic redistribution of carbonyl groups onto the degrees of hydration. The proportion of moderately hydrated carbonyl groups increases, apparently due to the deepening of pirfenidone into the circumpolar region of the bilayer. For the first time, a change in the microenvironment of pirfenidone upon binding to liposomes was shown: aromatic moiety interacts with the bilayer.

Liposomal Forms of Fluoroquinolones and Antifibrotics Decorated with Mannosylated Chitosan for Inhalation Drug Delivery

“…In contrast, for pirfenidone, cholesterol appeared to be a very important addition to the lipid bilayer. Cholesterol changes the way of interaction between carbonyl groups of lipids in DPPC and DPPC:Chol 90:10 vesicles and causes a dramatic redistribution of carbonyl groups onto the degrees of hydration [46]. Thus, according to the studies at the room temperature liposomes seems to be a suitable carrier for both fluoroquinolones and pirfenidone, so it agrees with previously published data concerning using of liposomes for several innovative drug [55] and gene [56] delivery systems.…”

“…Cardiolipin contributes to a small but statistically significant (p < 0.05) increase of EE, indicating a potential interaction between pirfenidone and lipid anionic groups. As it was previously demonstrated [46] even 10% of cholesterol in DPPC matrix leads to a decrease of EE, probably caused by more rigid membrane.…”

“…We have previously conducted primary studies on the physicochemical properties of liposomal moxifloxacin (DPPC:CL 80:20) [14], levofloxacin (DPPC and DPPC:CL 80:20) [16,45], and pirfenidone (DPPC and DPPC:Chol 90:10) [46]. Here, we aim to conduct a fundamental analysis of the influence of the composition of the lipid matrix on the properties of the liposomal form of these drugs.…”

A Label‐Free Multitechnique Approach to Characterize the Interaction of Bioactive Compounds with Biomimetic Interfaces

“…This observation, along with the dehydration observed by the upward increase in ν s (PO 2 − ), and the increased A[ ν (C═O free )]/A[ ν (C═O bond )] ratio, suggest the formation of hydrogen bonds between Chol and the polar headgroup of DPPC, in line with the umbrella model of Chol interaction with lipids. [ 40 ] Furthermore, the increased I [ ν as (CH 3 )]/ I [ ν s (CH 2 )] ratio and decreased I [ ν as (CH 2 )]/ I [ ν s (CH 2 )] ratio suggest increased membrane fluidity and rotational motion and reduced lateral packing (Table 3).…”

Beta-Caryophyllene Induces Significant Changes in the Lipid Bilayer at Room and Physiological Temperatures: ATR-FTIR Spectroscopy Studies

“…Carbonyl group spectral region deconvolution was conducted as described [13]. Curvefitting was performed using the Bruker Opus 7.5 software.…”