Spatial Distribution of Hydrophobic Drugs in Model Nanogel-Core Star Polymers

Abstract

Star polymers with a cross-linked nanogel core are promising carriers of cargo for therapeutic applications due to the synthetic control of amphiphilicity of arms and stability at infinite dilution. Three nanogel-core star polymers were investigated to understand how the arm-block chemical structure controls loading efficiency of a model drug, ibuprofen, and its spatial distribution. The spatial distribution profiles of hydrophobic core, hydrophilic corona, and encapsulated drug were determined by small-angle neutron scattering (SANS). SANS provides the nanometer-scale sensitivity to determine how the arm-block chemistry enhances the sequestering of ibuprofen. Validated molecular dynamics simulations capture the trends in drug profile and polymer segment distribution with further details on drug orientation distribution. This work provides a basis to study structure-function relationships in macromolecular-based carriers of cargo and represents a path toward validated and predictive simulation.

Influence of Solvent on the Drug-Loading Process of Amphiphilic Nanogel Star Polymers

“…We have successfully simulated ibuprofen uptake in simple adamantane-core model star polymers, and we can imagine using the atomistic nanogel polymeric system while varying the drug and solvent combinations. Recent SANS experiments, 14 in which ibuprofen was loaded into a PVL−PEG nanogel star polymeric nanoparticle using THF, indicate that the drug molecules do not penetrate the cross-linked core, but rather reside in the intermediate layer of PVL that is part of the diblock arm. Our simulations of these nanoparticles, initiated from semicollapsed structures in THF, indicate that the core would not be accessible to solvent, but the PVL arm block would be.…”

“…For example, a currently unresolved issue is whether loaded drugs reside within the interior volume of the hydrophobic core of the nanoparticle, or if they are more stably situated at the interface between the hydrophobic material and the surrounding water. Experiments and simulations , have produced preliminary findings that the latter might be the case, but detailed knowledge in this area remains forthcoming. In addition to drug-loading efficiency, it is also important to be able to control the rate of drug release, which has important therapeutic implications, since the rapid release of drug molecules has the potential to lead to harmful side effects.…”

A Mini‐Review on the Application of Computational Strategies in Multi‐Armed Star‐PEG Polymeric Micelles for Drug Delivery

“…More recently, Guangmin et. al [83] . conducted MD modeling in combination with small angle neutron scattering (SANS) to shed insight into the spatial distribution profile of the hydrophobic core, hydrophilic corona, and encapsulating drug ibuprofen.…”

“…al. [83] conducted MD modeling in combination with small angle neutron scattering (SANS) to shed insight into the spatial distribution profile of the hydrophobic core, hydrophilic corona, and encapsulating drug ibuprofen The low itraconazole loading in PEG-b-poly(lactide-co-glycolide)(PEG-b-PLGA) PM [84] was further investigated using MD simulations. It was found that drug loading occurs mainly at the water-polymer interfaces, while the interior of the micelle remained largely empty.…”

Reactive Self‐Assembly and Specific Cellular Delivery of NCO‐sP(EO‐stat‐PO)‐Derived Nanogels

“…Radically polymerized disulfide‐functional polyacrylates with oligoethyleneglycol side chains for hydrophilicity have been used to form nanogels in an emulsion‐free process . Star‐shaped block copolymer‐based molecules with a hydrophobic core have been used to generate core cross‐linked nanoparticles that can be loaded with hydrophobic guest molecules . We reported before that reactive star‐shaped prepolymers with a sorbitol core and a statistically copolymerized backbone of 80% ethylene oxide and 20% propylene oxide that have been endowed with isocyanate groups at the distal endings of the arms NCO‐sP(EO‐stat‐PO) can be used to prepare nanogels without using surfactants or solvents .…”