Abstract
Fully atomistic molecular dynamics simulations are employed to study in detail the interactions between a complex comprised by a PEGylated hyperbranched polyester (HBP) and doxorubicin molecules, with a model dipalmitoylphosphatidylglycerol membrane in an aqueous environment. The effects of the presence of the lipid membrane in the drug molecules’ spatial arrangement were examined in detail and the nature of their interaction with the latter were discussed and quantified where possible. It was found that a partial migration of the drug molecules towards the membrane’s surface takes place, driven either by hydrogen-bonding (for the protonated drugs) or by hydrophobic interactions (for the neutral drug molecules). The clustering behavior of the drug molecules appeared to be enhanced in the presence of the membrane, while the development of a charge excess close to the surface of the hyperbranched polymer and of the lipid membrane was observed. The uneven charge distribution created an effective overcharging of the HBP/drug complex and the membrane/drug surface. The translational motion of the drug molecules was found to be strongly affected by the presence of the membrane. The extent of the observed changes depended on the charge of the drug molecule. The build-up of the observed charge excesses close to the surface of the polymeric host and the membrane, together with the changes in the diffusional behavior of the drug molecules are of particular interest. Both phenomena could be important at the latest stages of the liposomal disruption and the release of the drug cargo in formulations based on relevant liposomal carriers.
Highlights
Vesicles based on lipids are recognized as promising non-viral vectors for drug or gene delivery purposes [1,2,3,4,5]
In this work we examine by means of fully atomistic molecular dynamics simulations, environment
As was demonstrated by the analysis presented, the presence of the DPPG membrane imparts significant changes regarding the spatial distribution and the clustering behavior of the drug molecules
Summary
Vesicles based on lipids are recognized as promising non-viral vectors for drug or gene delivery purposes [1,2,3,4,5]. This attribute of DPPG lipids can be exploited in more complex drug/liposome formulations, where negative chargeofper at physiological pH conditions [14,15] which them candidates optimization thelipid drug loading conditions is promoted by therenders presence of good multifunctional when complexation with cationic bioactive compounds is desired [13,14,16] This attribute of DPPG molecules such as hyperbranched polymers [4,17,18]. LipidsIn can be exploited more complex drug/liposome formulations, where optimization of the drug this work we in examine by means of fully atomistic molecular dynamics simulations, the loading conditions is promoted by the presence of multifunctional molecules such as hyperbranched interactions of a complex comprised by a functionalized (PEGylated) hyperbranched polymer (HBP). Distributions related to possible overcharging phenomena of the polymer and of the bilipid DPPG layer, and theand changes in the translational behavior of the drug molecules imparted by the presence of
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