On the phase behaviour of pure PSPC and PEGylated multi-component lipid and their interaction with Paclitaxel: An all-atom MD study

TL;DR

This study uses all-atom molecular dynamics to analyze the phase behavior of pure and PEGylated multi-component lipid membranes and their interactions with Paclitaxel, revealing temperature-dependent phase transitions and enhanced drug interaction due to PEGylation.

Contribution

It provides detailed insights into the phase transitions of pure and PEGylated lipid membranes and demonstrates PEG's role in promoting Paclitaxel interaction, advancing drug delivery research.

Findings

Pure PSPC transitions from gel to liquid crystalline phase between 320-330 K.

PEGylation enhances Paclitaxel interaction with lipid bilayers.

Paclitaxel interacts more readily with membranes above transition temperature.

Abstract

The study of the structural behaviour of pure and multi-component lipids at various temperatures and the interaction of these multi-component lipids with pharmaceutically important drugs carry huge importance. Here, we investigated the phase behaviour of the pure PSPC (1-palmitoyl-2-stearoyl-sn-glycero-3-phosphocholine), and multicomponent PSPC and DSPE-PEG2000(1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[amino(polyethylene glycol)-2000]) membranes at seven different temperatures ranging from 280 K to 360 K, and calculated their structural properties. We observe a transition from the gel phase to the liquid crystalline phase between 320 K and 330 K in agreement with experimental reports for pure PSPC. PSPC remained in the tilted gel phase L\b{eta}$'$ at 320 K and 310 K, entered the 'mixed ordered' domain with a partially interdigitated region at 300 K, and finally formed the sub gel phase at 280 K. We studied the self-assembly for the multicomponent PSPC and DSPE-PEG2000 membranes and found the coexistence of ordered and disordered phases at 320 K. In comparison to the pure PSPC, for multicomponent system, this transition was gradual, and a complete liquid crystalline to gel phase transformation occurred between 320 K and 310 K. We further studied the interaction of Paclitaxel with pure PSPC and PEGylated multicomponent lipid bilayers using umbrella sampling technique and observed PEG promotes the interaction of Paclitaxel with the later one in comparison to the former. Above the bilayer transition temperature, Paclitaxel interacts more with the bilayer and enters inside the bilayer easily for both systems. Understanding of structural and interaction behaviour of the PEGylated multicomponent lipid bilayers with Paclitaxel will help explore Paclitaxel based drug applications in the future.