Drug-Induced Morphology Transition of Self-Assembled Glycopolymers: Insight into the Drug–Polymer Interaction

Abstract

It is often assumed that a hydrophobic drug will be entrapped in the hydrophobic environment of a micelle. Little attention is usually drawn to the actual location of the drug and the effect of the drug on properties. In this publication, we show how the chosen drug curcumin is not only unexpectedly located in the shell of the micelle but also that the accumulation in the hydrophilic block can lead to changes in morphology during self-assembly. A block copolymer poly(1-O-methacryloyl-β-D-fructopyranose)-b-poly(methyl methacrylate), poly(1-O-MAFru) 36 -b-PMMA 192 , was loaded with different amounts of curcumin. The resulting self-assembled nanoparticles were analyzed using transmission electron microscopy, small-angle X-ray scattering (SAXS), and small-angle neutron scattering (SANS). Initial microscopy evidence revealed that the presence of the drug induces morphology changes from cylindrical micelles (no drug) to polymersomes, which decreased in size with increasing amount of drug. SAXS and SANS analysis, supported by fluorescence studies, revealed that the drug is interacting with the glycopolymer block. The drug influenced not only the shape of the drug carrier but also the level of hydration of the shell. Increasing the amount of drug dehydrated the nanoparticle shell, which coincided with a lower nanoparticle uptake by MCF-7 breast cancer cells and noncancerous RAW 264.7 cells. As a result, we showed that the drug can influence the behavior of the nanoparticle in terms of shape and shell hydration, which could influence the performance in a biological setting. Although the depicted scenario may not apply to every drug carrier, it is worth evaluation if the drug will interfere in unexpected ways.

Loading‐Dependent Structural Model of Polymeric Micelles Encapsulating Curcumin by Solid‐State NMR Spectroscopy

“…This is in accordance with the strongly decreased dissolution rate as observed for CUR‐11‐P1 and an increased radius of the particle, because of the shell being more rigid for these ultrahigh loadings. This overall picture would suggest an increased hydrophobicity of the micelles at higher loadings in agreement with the results in Table and with a different study on glycopolymers using SAXS and SANS …”

“…This is in accordance with the strongly decreased dissolution rate as observed for CUR-11-P1 and an increased radius of the particle,b ecause of the shell being more rigid for these ultrahigh loadings.T his overall picture would suggest an increased hydrophobicity of the micelles at higher loadings in agreement with the results in Table 1a nd with ad ifferent study on glycopolymers using SAXS and SANS. [19] In general, structural information and understanding on the molecular level is difficult to obtain for drug-loaded polymeric micelles.I nt his work, we could show that solidstate NMR spectroscopy is av ersatile toolbox, which cancomplemented by other approaches-facilitate the detailed analysis of polymeric micelles,t hus improving our structural understanding.N MR spectroscopic data probed changes in the interaction profile with increasing loading. At higher loadings,t he hydrophilic polymer blocks were found to participate in the coordination of CUR, which is presumably of critical importance to obtain the unusually high drug loadings of approximately 50 wt.…”

A Micellar Mitotane Formulation with High Drug‐Loading and Solubility: Physico‐Chemical Characterization and Cytotoxicity Studies in 2D and 3D In Vitro Tumor Models

“…This drug–corona interaction can enable to ultra‐high drug loading or lead to colloidal instability of the formulation . However, the drug corona interaction can also affect the morphology, endocytosis, or prolong supersaturation . Interestingly, for the POx/POzi nanoformulations the drug was found fully amorphous in the precipitate, which also contains polymer .…”

Strukturmodell von Polymermizellen in Abhängigkeit von der Curcumin‐Beladung mithilfe von Festkörper‐NMR‐Spektroskopie

“…Ausd iesem Gesamtbild würde sich eine erhçhte Hydrophobizitätder Mizellen bei hçherer Beladung ableiten, was die Ergebnisse in Tabelle 1s owie verschiedene Untersuchungen an Glycopolymeren mit SAXS und SANS zeigen. [19] Die…”