Supramolecularly cross-linked nanoassemblies of self-immolative polyurethane from recycled plastic waste: high encapsulation stability and the triggered release of guest molecules

Abstract

Stabilizing noncovalently encapsulated guest molecules inside a nanoassembly constructed from amphiphilic polymers has become a very challenging effort in the area of targeted drug delivery of biomedical applications. The unwanted...

Stabilizing Entropically Driven Self-Assembly of Self-Immolative Polyurethanes in Water: A Strategy for Tunable Encapsulation Stability and Controlled Cargo Release

“…Figure depicts that the self-assembly for all of the polymers in water is enthalpically disfavored and entropy-driven, which is not very frequently found in the self-assembly of amphiphilic block-copolymers with large hydrophobic counterparts . However, it is more common in biological systems like β-amyloids, collagen fibrils, and bovine brain tubulin. , Here, for all of these polymers, the water molecules engaged in H-bonding with the urethane linker in the nonassembled state are expelled during the process of self-assembly as the self-assembled state is stabilized by the energetically favorable H-bonding between urethane linkers and π–π stacking, as evidenced by computational chemistry and the X-ray diffraction study ( d = 3.8 Å corresponds to the π–π stacking distance) (Figure S14). Thus, the release of water molecules to the bulk makes the process entropically favorable and therefore eventually drives the self-assembly in a positive direction.…”

“…To tune their self-assembly, it is of utmost importance to understand the driving force of self-assembly and the structural effect or solvent effect on the self-assembly behavior. Investigating their morphology, size, stability, guest encapsulation, and release capability is highly relevant in the context of their biological applications, more specifically in the area of drug delivery. − In this context, we are interested in the condensation polymerization of polyurethane , due to (i) the ease of synthesis, (ii) better opportunity for structural variations in the polymer backbone compared to chain polymerization, (iii) presence of a self-complementary H-bonding motif, and (iv) excellent biocompatibility. , Here, we have demonstrated a few significant aspects toward the development of a robust delivery platform: (i) molar mass controlled synthesis of polyurethane using bis-hydroxyethyl terephthalate (BHET), a monomer from recycled plastic waste; , (ii) thermodynamic insight of the self-assembly process; − (iii) stabilizing nanoassemblies by supramolecular cross-linking; − (iv) redox-responsive guest release; − and (v) tumor-relevant pH-induced surface charge modulation. , As plastic bottles are polluting the environment, the strategy of recycling plastic waste and making biodegradable polymers for biomedical applications can be considered an eco-friendly synthetic approach. Moreover, a detailed investigation of controlling the molar mass by time-dependent addition of monofunctional impurities (MFIs) in the course of polymerization has been scarcely reported in the literature.…”

“…Moreover, a detailed investigation of controlling the molar mass by time-dependent addition of monofunctional impurities (MFIs) in the course of polymerization has been scarcely reported in the literature. From the structural point of view, in most of the polyurethanes, amphiphilicity is introduced by incorporation of hydrophilic parts in the backbone and only a few reports are there related to hydrophilicity in the pendant, , which could be an added advantage in stabilization of entropy-driven self-assembled structures as it would not interfere in polymer chain folding and intrachain H-bonding among the urethane linkers. , There are very few reports on the thermodynamics of self-assembly of various organic dyes and polymers in water by Würthner et al and Ghosh et al, respectively. As the self-assembly of amphiphilic molecules in water is governed by thermodynamic parameters, an in-depth understanding of the thermodynamic profile would be very significant in fabricating stable self-assembled nanostructures toward theranostic applications. − Here, we elucidate the comparative self-assembly studies of series of polyurethanes with varying molar masses based on thermodynamic parameters determined by isothermal titration calorimetry (ITC), which reveals entropy-driven self-assembly similar to biological macromolecules.…”

“…From the structural point of view, in most of the polyurethanes, amphiphilicity is introduced by incorporation of hydrophilic parts in the backbone and only a few reports are there related to hydrophilicity in the pendant, 42,43 which could be an added advantage in stabilization of entropy-driven selfassembled structures as it would not interfere in polymer chain folding and intrachain H-bonding among the urethane linkers. 44,45 There are very few reports on the thermodynamics of self-assembly of various organic dyes and polymers in water by Wurthner et al 46 and Ghosh et al, 29 respectively. As the self-assembly of amphiphilic molecules in water is governed by thermodynamic parameters, an in-depth understanding of the thermodynamic profile would be very significant in fabricating stable self-assembled nanostructures toward theranostic applications.…”

Bioderived Lipoic Acid-Based Dynamic Covalent Nanonetworks of Poly(disulfide)s: Enhanced Encapsulation Stability and Cancer Cell-Selective Delivery of Drugs

“…The heat change associated with the disassembly of the nanoaggregates is documented in the ITC experiment, and from the data, enthalpy of micellization and other thermodynamic parameters associated with the self-assembly process are calculated using the equations reported in the literature. 79,80 In the ITC dilution experiment of GS solution at 25 °C, an exothermic heat flow was observed, which eventually saturated beyond a certain concentration (considered CAC), as there was no more disassembly of micelles. The exothermic heat change (ΔH = −0.2 kcal/mol) in disassembly makes the process enthalpically favorable, and on the contrary, self-assembly becomes an enthalpically disfavored process (ΔH = 0.2 kcal/mol) (Figure 2a), which is previously found for other systems as well.…”