Synthesis and characterization of IUdR loaded PEG/PCL/PEG polymersome in mixed DCM/DMF solvent: Experimental and molecular dynamics insights into the role of solvent composition and star architecture in drug dispersion and diffusion

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Sepideh Khoee, Ali Hashemi, Sajjad Molavipordanjani
Combined experimental and simulation investigations have provided molecular level insights into 5-iodo-2′-deoxyuridine (IUdR) loading behavior for the novel PEG/PCL/PEG polymersome-like carriers in mixed dichloromethane/N,N-dimethylformamide (DCM/DMF) solvent. As with the experiments, a novel approach was applied for layer by layer tailoring of polyethylene glycol (PEG) and polycaprolactone (PCL) as PEG/PCL/PEG copolymer on the surface of magnetite nanoparticles (MNPs) by click chemistry. Experimental results indicated that IUdR, as an anti-cancer drug, could be encapsulated up to 80% EE in this nanocarrier and could be in-vitro released up to 90% during 120h. Computational studies, on the other hand, provide molecular level insights into the optimal performance of the carrier in terms of drug "Dispersion" and "Diffusion" patterns in equimolar DCM/DMF solvent. Molecular dynamics simulations of the system in four distinct solvation scenarios including pure DCM, mixed DCM/DMF, pure DMF and water, have proven that while hydrophobic solvents give rise to better "dispersion" of drugs, hydrophilic solvents lead for drug molecules to penetrate into the carrier and improve "diffusion" properties. Optimal conditions for drug encapsulation, as also confirmed through experiments, was observed for mixed DCM/DMF solvent in terms of proper diffusion and well dispersion. While drug "aggregates" were observed in DCM, poorly stable drug molecules with lowered penetrations were observed in pure DMF. Proper release properties with IUdR molecules staying on the surface of the carrier was also observed in water. The interesting role of the star-linear architecture was further scrutinized through distinctions made through analysis of interactions between IUdR molecules with "inner" and "outer" PEG sections.

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