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.
Highlights
Today, all over the world, there is an urgent task of developing new drugs for rehabilitation after COVID-19
While UV spectroscopy is well suited for analyzing pirfenidone content and determining liposome loading efficiency, the ATR-FTIR spectrum of PF appears to be useful for deeper analysis of the microenvironment of its functional groups (Table 1, Figures 1b and S1)
Liposomal forms of pirfenidone were obtained via passive loading, and the loading efficiency depends on the membrane rigidity: the addition of cholesterol reduces the loading efficiency
Summary
All over the world, there is an urgent task of developing new drugs for rehabilitation after COVID-19. For the massive use of pirfenidone in the rehabilitation of patients with post-COVID pulmonary fibrosis and IPF, a simple and convenient dosage form is needed, which would not require a hospital stay and at the same time ensure high efficiency of therapy, including high bioavailability in the target lung tissues. Such a dosage form can be an inhaled liposomal form of pirfenidone, including one based on dipalmitoylphosphatidylcholine (DPPC), a major phospholipid of human lung surfactant [8]. We set the goal of studying the effect of the composition of the lipid matrix on the nature of the interaction of liposomes with pirfenidone using sophisticated spectral methods, primarily ATR-FTIR spectroscopy
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