Design of Amphiphilic, Biodegradable Functionalized Polyoxazoline Hybrid-Block Graft Copolymers Using Click Reactions

Abstract

Hybrid molecular brushes (HMBs), or bottlebrush polymers, are polymeric constructs containing a linear polymeric backbone and polymeric side chains with different chemical characteristics. Hybrid-block graft copolymers (HCPs) are similar to traditional HMBs, except their backbone consists of more than one polymer. We developed a facile method for the synthesis of a family of amphiphilic, biodegradable HCPs composed of two blocks: a hydrophilic block of poly(ethylene glycol) and a hydrophobic block of poly(2-oxazolines) modified by side chains of polycaprolactone. This was achieved by modification of the precursor 2-oxazoline monomers with a thiol-containing compound via a thiol−ene click chemistry reaction, followed by ring-opening polymerization of the monomer initiated by a poly(ethylene glycol) methyl ether tosylate macroinitiator. Lastly, polycaprolactone side chains were grafted via ring-opening polymerization yielding the amphiphilic HCPs. Herein, we determined the critical micelle concentration (cmc), showed the uptake and partitioning of β-carotene in the micelles, and studied the brush architecture. The chemical structure, molecular weight, and morphology of the functionalized backbone, block copolymers, and HCPs were also determined.

Size- and Shape-controlled Biodegradable Polymer Brushes Based on l-Amino Acid for Intracellular Drug Delivery and Deep-Tissue Penetration

“…1−4 Polymer brushes are typically synthesized by grafting-to and grafting-from strategies on the well-defined rigid polymer backbone with flexible side-chains for self-assembly in solution and solid state (in thin films). 5−7 Plug-and-play interfaces for guest−host interaction, 8 protein conjugates, 9 hybrid molecular brushes, 10 cross-linkable block copolymer brushes, 11 NIR probe tagged triblock micelles, 12 and bottlebrush adhesives 13 are some of the recent examples reported for multifaceted polymer brushes. Polymer brushes for biomedical field is typically achieved by incorporating hydrophilic−hydrophobic balance in combination with pH, redox, or thermal stimuli-responsiveness to impart on-demand delivery of cargoes at the intracellular compartments and tumor-specific environments.…”

“…Polymer brushes are higher-order synthetic macromolecules of discrete nanocompartmentalization and provide unique opportunities to precisely control one- and three-dimensional shapes, subnanometer size objects and surfaces, and chemical functions, and they offer unlimited opportunity for application in material science and biomedical field. − Polymer brushes are typically synthesized by grafting-to and grafting-from strategies on the well-defined rigid polymer backbone with flexible side-chains for self-assembly in solution and solid state (in thin films). − Plug-and-play interfaces for guest–host interaction, protein conjugates, hybrid molecular brushes, cross-linkable block copolymer brushes, NIR probe tagged triblock micelles, and bottlebrush adhesives are some of the recent examples reported for multifaceted polymer brushes. Polymer brushes for biomedical field is typically achieved by incorporating hydrophilic–hydrophobic balance in combination with pH, redox, or thermal stimuli-responsiveness to impart on-demand delivery of cargoes at the intracellular compartments and tumor-specific environments. , Among many choices to introduce amphiphilicity in the polymer system, polyethylene glycols (PEG) and their derivatives emerged as a primary choice due to their biocompatibility, nonimmunogenicity, nonhemolytic properties, etc.…”

Permeability of Skin-Mimicking Cell Coatings by Polymers of Complex Architecture Based on Polyoxazolines

“…Micelle-forming nanocarriers have been shown to surpass the SC without damaging the tissue while efficiently delivering therapeutics [11,12]. We previously reported on the synthesis of a family of bio-benign amphiphilic poly(2-oxazoline)-based block copolymers (BCPs) and hybrid block-graft copolymers (HCPs) [13]. Poly(2-oxazolines) are a family of emerging innovative biomaterials that demonstrate notable results compared to other polymeric therapeutics [14][15][16].…”

“…Polymers functionalized with aminothiophenol (A) and cysteamine (B) were studied. The compositions of the polymers were established using 1 H NMR, Size-Exclusion Chromatography and fluorescence of FITC-labelled amino groups [13]; they are summarized in Table 1. The most widely used biodegradable polymer for drug delivery is PEG.…”

“…Polymers functionalized with aminothiophenol (A) and cysteamine (B) were studied. The compositions of the polymers were established using 1 H NMR, Size-Exclusion Chromatography and fluorescence of FITC-labelled amino groups [13]; they are summarized in Table 1. Fluorescein isothiocyanate isomer I (FITC, ≥90% (HPLC)), dimethyl sulfoxide (DMSO) (anhydrous, ≥99.9%), ethanol (anhydrous, 99%), diethyl ether (anhydrous, ACS reagent, ≥99%, contains BHT as inhibitor), and Pur-A-Lyzer™ Mega 6000 Da Dialysis Kit were purchased from Sigma-Aldrich and used without purification.…”