In this study, a temperature sensitive graft carbon dioxide-based copolymer, poly (propylene oxide-co-carbon dioxide-co-allyl glycidyl ether)-poly (N-isopropylacrylamide)-polyethylene glycol monomethyl ether (PPAG-PNIPAm-mPEG) was synthesized by “Click Chemistry”. The hydrophobic main chain, PPAG, was prepared by the copolymerization of propylene oxide (PO) and allyl glycidyl ether (AGE). The branch chains include hydrophilic mPEG and temperature sensitive poly (N-isopropylacrylamide). The structure of the polymer was characterized by 1 H NMR and IR spectroscopy. Avermectin (AVE) was loaded into the nanoparticles to form PPAG-PNIPAm-mPEG@AVE nanoparticles. PPAG-PNIPAm-mPEG could self-assemble into nano-sized micelles in aqueous solution. And the size, zeta potential, critical micelle concentration (CMC) of PPAG-PNIPAm-mPEG nanoparticles can be altered by changing the lengths of the PNIPAm segments. The loading rate and encapsulation rate of PPAG-PNIPAm-mPEG@AVE were 36.98% and 89.98% respectively. The temperature sensitiveness of the nanomaterials was confirmed by DLS. The results show that temperature has a certain effect on the AVE release rate of PPAG-PNIPAm-mPEG@AVE in vitro. With the decrease of PNIPAm chain length, the AVE release rate decreases, and the contact angle of PPAG-PNIPAm-mPEG@AVE decreases compared with that of water.
Xiao Duan,Qiang Wang,Yue Wang,Xinping Liu,Manman Lu,Zhifang Li,Xuelian Jiang,Jingquan Ji
Using an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis. The carboxyl groups in L-glutathione oxidized were reacted with the hydroxyl group in paclitaxel (PTX) using the catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Then, the amino-polyethylene glycol monomethyl ether (mPEG-NH2) was conjugated with GSSG to prepare PTX-GSSG-PEG. The structure of PTX-GSSG-PEG was characterized using infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). The drug release kinetics of PTX within PTX-GSSG-PEG were quantified using ultraviolet spectroscopy (UV-Vis). The size of the PTX-GSSG-PEG micelles was 83 nm, as evaluated using dynamic light scattering (DLS), and their particle size remained stable in a pH 7.4 PBS for 7 days. Moreover, the micelles could responsively degrade and release PTX in a reduced glutathione environment. The drug loading of PTX in PTX-GSSG-PEG was 13%, as determined using NMR. Furthermore, the cumulative drug release rate of PTX from the micelles reached 72.1% in a reduced glutathione environment of 5 mg/mL at 120 h. Cell viability experiments demonstrated that the PTX-GSSG-PEG micelles could induce the apoptosis of MCF-7 cells. Additionally, cell uptake showed that the micelles could distribute to the cell nuclei within 7 h. To sum up, with this glutathione-responsive paclitaxel prodrug micelle based on the endogenous molecule GSSG, it may be possible to develop novel nanomedicines in the future.
Yuanyuan Xu,Youcheng Li,Xueteng Cao,Qijing Chen,Zesheng An
Reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization in cononsolvents of poly(N-isopropylacrylamide) (PNIPAM) was developed as a versatile strategy for the synthesis of thermoresponsive nanogels with controlled composition, functionality and architecture. Cononsolvents composed of mixtures of methanol, ethanol and isopropanol with water were first screened for their suitability as the media for dispersion polymerization of NIPAM, and water–ethanol (75 : 25, v : v) solution was selected due to good RAFT control, efficient formation of nanogels and low toxicity. RAFT dispersion polymerization of NIPAM in the cononsolvent using poly(N,N-dimethylacrylamide) (PDMA) as the macromolecular chain transfer agent (Macro-CTA) showed good control over the molecular weight, polydispersity and pseudo linear polymerization kinetics, as characterized by gel permeation chromatography (GPC) and 1H NMR. The effect of the molecular weight of Macro-CTA, the degree of polymerization of PNIPAM, the molar ratio of [crosslinker] : [Macro-CTA] and the solid content on the formation and size of nanogels was investigated. The thermal profiles of nanogels were characterized by dynamic light scattering (DLS) both in cononsolvents and water. This cononsolvency strategy for dispersion polymerization was shown to be compatible with the incorporation of hydrophilic comonomers of N-(2-hydroxyethyl)acrylamide (HEAM) and diacetone acrylamide (DAAM). The nanogel containing DAAM was demonstrated for postpolymerization modification using ketone–alkoxyamine chemistry. More importantly, dispersion polymerization in cononsolvents allowed various hydrophobic components, e.g. butyl acrylate (BA), fluorescein O-acrylate (FLA), and 1,6-hexanediol diacrylate (HDDA), to be reliably copolymerized with NIPAM, showing well controlled polymerization, composition, nanogel size and colloidal stability. Finally, an amphiphilic block copolymer PDMA-b-PBA was used as a Macro-CTA to produce the PDMA-b-PBA-b-PNIPAM triblock copolymer and triple-layered nanogel, taking advantage of the solubility of PDMA-b-PBA and the insolubility of PNIPAM in the water–ethanol solution at the polymerization temperature.
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