Bioreducible and core‐crosslinked hybrid micelles from trimethoxysilyl‐ended poly(ε‐caprolactone)‐S‐S‐poly(ethylene oxide) block copolymers: Thiol‐ene click synthesis and properties

Abstract

Bioreducible and core‐crosslinked hybrid micelles were for the first time fabricated from biodegradable and biocompatible trimethoxysilyl‐terminated and disulfide‐bond‐linked block copolymers poly(ε‐caprolactone)‐S‐S‐poly(ethylene oxide), which were prepared by combining thiol‐ene coupling reaction and ring‐opening polymerization. The molecular structures, physicochemical, self‐assembly, and bioreducible properties of these copolymers were thoroughly characterized by means of FTIR, 1H NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, dynamic light scattering (DLS), and transmission electron microscopy. The core‐crosslinking sol‐gel reaction was confirmed by 1H NMR, and the core‐crosslinked hybrid micelles contained about 3 wt % of silica. The bioreducible property of both uncrosslinked and core‐crosslinked micelles in 10 mM 1,4‐dithiothreitol (DTT) solution was monitored by DLS, which demonstrated that the PEO corona gradually shedded from the PCL core. The anticancer doxorubicin drug‐loaded micelles showed nearly spherical morphology compared with blank micelles, presenting a DTT reduction‐triggered drug‐release profile at 37 °C. Notably, the core‐crosslinked hybrid micelles showed about twofold drug loading capacities and a half drug‐release rate compared with the uncross‐liked counterparts. This work provides a useful platform for the fabrication of bioreducible and core‐crosslinked hybrid micelles potential for anticancer drug delivery system. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Amphiphilic copolymers with pendent carboxyl groups for high-efficiency loading and controlled release of doxorubicin

“…mPEG-b-PATMC-g-SCH 2 COOH was synthesized by the thiol-ene "click" reaction [25][26][27]. 0.28 g (0.801 mmol allyl groups) of mPEGb-PATMC was dissolved in 3 ml of anhydrous tetrahydrofuran (THF) followed by adding 4.003 mmol (0.368 g) of thioglycolic acid and 4.003 mmol (0.657 g) of AIBN under a N 2 atmosphere.…”

The synthesis of peptide‐conjugated poly(2‐ethyl‐2‐oxazoline)‐b‐poly(L‐lactide) (PEtOx‐b‐PLA) polymeric systems through the combination of controlled polymerization techniques and click reactions

“…Subsequently, (Figure 1a), supports the formation of 4. Furthermore, the peaks at 5.8 and 5.4 were assigned to allyl (1H, CH2=CH-CH2-) and (2H, CH2=CH-CH2-), respectively and they support the presence of allyl group on 4 [46][47][48][49]. In FT-IR of 4 (Figure 1b), the stretching of allyl group falls in overcrowded 1600-1700 cm -1 region, thus; FT-IR spectrum of 4 fails to confirm the presence of allyl group.…”

Disulfide-Bridged Cleavable PEGylation in Polymeric Nanomedicine for Controlled Therapeutic Delivery

“…The cross-linker is typically employed with the S-S moiety. These include cystamine dihydrochloride [22,25,26,43,[50][51][52][53][54], 2,2-dithiodiethanol (DTDE) [55,56], 3,3′-dithiodipropionic acid (DPA) [57][58][59][60], N,N′-cystaminebisacrylamide [61], 2,2′-dithiodipyridine [27,44,62], 2-(pyridyldithio)-propionic acid [63], cystamine bisacrylamide [64], N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) [65,66] and sulfosuccinimidyl 6-(3′-[2-pyridyldithio]-propionamido) hexanoate (sulfo-LC-SPDP) [67]. Alternative approaches involve conjugation of the thiol group (-SH) with PEG or other polymers, and subsequent oxidation of -SH with oxidants such as N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) [68] and pyridyl disulfide carbonate [69] in order to form the S-S bond.…”