Drug-dependent morphological transitions in spherical and worm-like polymeric micelles define stability and pharmacological performance of micellar drugs

Significant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy has not been adequately addressed. We addressed this gap by assessing pharmacological efficacy of polymeric micelles with spherical and wormlike morphologies. We observed that poly(2 oxazoline) based polymeric micelles can be elongated over time from a spherical structure to wormlike structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. We further evaluated the role of different morphologies of olaparib micelles on pharmacological performance against a triple negative breast cancer tumor (TNBC) model. Spherical micelles accumulated rapidly in the tumor tissue while retaining large amounts of drug; wormlike micelles accumulated more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles.

Hydrophobic Biomimetic Nanoparticles drives Size-dependent Remodelling in Asymmetric Bilayers

The interactions between heterogeneous components in a biomimetic bilayer can control its physical properties such as its rigidity, local and bulk curvature and propensity towards phenomena such as membrane fission and fusion. In particular, nanoparticles (NPs) have been subjects of intense interest due to their similar scale to the bilayer width and its ability to affect local membrane structure. Generally, it is understood that hydrophobic components are energetically favoured to adsorb within the hydrophobic interior of a biomimetic bilayer. However, how such NPs interact in the presence of heterogeneous aggregates in the bilayer has been the subject of much debate. To better understand the effects of the integration of nanoscale components on heterogeneous mixed bilayer, we have simulated a series of generic hydrophobic NPs interacting with a phase-separating two-component surfactant bilayer. We find that the hydrophobic NP tends to aggregate at the phase interface, acting as a line tension relaxant i.e. a lineactant on the phase separated interface, which results in a variety of demixing behavior. We demonstrate that depending on the size of the NP, the localized softening of surfactants and the formation of a mixing gradient of surfactants can drive the a cap/bud formation around the NP, as well as the formation of a NP-micelle structure<br>

Hydrophobic Biomimetic Nanoparticles drives Size-dependent Remodelling in Asymmetric Bilayers

The interactions between heterogeneous components in a biomimetic bilayer can control its physical properties such as its rigidity, local and bulk curvature and propensity towards phenomena such as membrane fission and fusion. In particular, nanoparticles (NPs) have been subjects of intense interest due to their similar scale to the bilayer width and its ability to affect local membrane structure. Generally, it is understood that hydrophobic components are energetically favoured to adsorb within the hydrophobic interior of a biomimetic bilayer. However, how such NPs interact in the presence of heterogeneous aggregates in the bilayer has been the subject of much debate. To better understand the effects of the integration of nanoscale components on heterogeneous mixed bilayer, we have simulated a series of generic hydrophobic NPs interacting with a phase-separating two-component surfactant bilayer. We find that the hydrophobic NP tends to aggregate at the phase interface, acting as a line tension relaxant i.e. a lineactant on the phase separated interface, which results in a variety of demixing behavior. We demonstrate that depending on the size of the NP, the localized softening of surfactants and the formation of a mixing gradient of surfactants can drive the a cap/bud formation around the NP, as well as the formation of a NP-micelle structure<br>

Biocompatible PEO-b-PCL Nanosized Micelles as Drug Carriers: Structure and Drug–Polymer Interactions

We report on the preparation of drug nanocarriers by encapsulating losartan potassium (LSR) into amphiphilic block copolymer micelles, utilizing the biocompatible/biodegradable poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL) diblock copolymer. The PEO-b-PCL micelles and LSR-loaded PEO-b-PCL nanocarriers were prepared by organic solvent evaporation method (OSEM). Light scattering and nuclear magnetic resonance (NMR) provide information on micelle structure and polymer–drug interactions. According to dynamic light scattering (DLS) analysis, the PEO-b-PCL micelles and LSR-loaded PEO-b-PCL nanocarriers formed nanostructures in the range of 17–26 nm in aqueous milieu. Attenuated total reflection Fourier transform infrared (ATR-FTIR) and ultraviolet-visible (UV-Vis) measurements confirmed the presence of LSR in the polymeric drug solutions. NMR results proved the successful encapsulation of LSR into the PEO-b-PCL micelles by analyzing the drug–micelles intermolecular interactions. Specifically, 2D-NOESY experiments clearly evidenced the intermolecular interactions between the biphenyl ring and butyl chain of LSR structure with the methylene signals of PCL. Additionally, NMR studies as a function of temperature demonstrated an unexpected, enhanced proton mobility of the PEO-b-PCL micellar core in D2O solutions, probably caused by the melting of the PCL hydrophobic core.

Hydrophobic Nanoparticles Drives Size-Dependent Remodelling in Asymmetric Bilayers

The interactions between heterogeneous components in a biomimetic bilayer controls its physical properties such as its rigidity, local and bulk curvature and propensity towards phenomena such as membrane fission and fusion. In particular, membrane proteins (MPs) and nanoparticles (NPs) have been subjects of intense interest due to their similar scale to the bilayer width and because of their ability to affect local membrane structure. However, how such NPs interact in the presence of heterogeneous aggregates in the bilayer has been the subject of much debate, especially its effect on raft-like structures. To better understand the effects of hydrophobic integration of nanoscale components on such raft-like structures, we have simulated a series of generic hydrophobic NPs interacting with a phase-separating two-component surfactant bilayer. We find that the hydrophobic NP tends to aggregate at the phase interface, acting as a line tension relaxant i.e. a lineactant on the phase separated interface, which results in differing demixing behavior. In particular, we demonstrate that depending on the size of the NP, the effect of the line tension can drive the a cap/bud formation around the NP, ultimately resulting in the formation of a NP-micelle structure.<br><br>

Hydrophobic Nanoparticles Drives Size-Dependent Remodelling in Asymmetric Bilayers

The interactions between heterogeneous components in a biomimetic bilayer controls its physical properties such as its rigidity, local and bulk curvature and propensity towards phenomena such as membrane fission and fusion. In particular, membrane proteins (MPs) and nanoparticles (NPs) have been subjects of intense interest due to their similar scale to the bilayer width and because of their ability to affect local membrane structure. However, how such NPs interact in the presence of heterogeneous aggregates in the bilayer has been the subject of much debate, especially its effect on raft-like structures. To better understand the effects of hydrophobic integration of nanoscale components on such raft-like structures, we have simulated a series of generic hydrophobic NPs interacting with a phase-separating two-component surfactant bilayer. We find that the hydrophobic NP tends to aggregate at the phase interface, acting as a line tension relaxant i.e. a lineactant on the phase separated interface, which results in differing demixing behavior. In particular, we demonstrate that depending on the size of the NP, the effect of the line tension can drive the a cap/bud formation around the NP, ultimately resulting in the formation of a NP-micelle structure.<br><br>