Novel Temperature/Reduction Dual-Stimulus Responsive Triblock Copolymer [P(MEO2MA-co- OEGMA)-b-PLLA-SS-PLLA-b-P(MEO2MA-co-OEGMA)] via a Combination of ROP and ATRP: Synthesis, Characterization and Application of Self-Assembled Micelles.

Fei Song,Wenli Gao,Zhidan Wang,Qingrong Wu,Yu Fu,Shouxin Liu

doi:10.3390/polym12112482

Abstract

Novel temperature/reduction dual stimulus-responsive triblock copolymers, poly [2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate]-b-(L-polylactic acid)-SS-b-(L-polylactic acid)-b-poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo(ethylene glycol)methacrylate] [P(MEO2MA-co-OEGMA)-b-PLLA-SS-PLLA-b-P(MEO2MA-co-OEGMA)] (SPMO), were synthesized by ring opening polymerization (ROP) of L-lactide and 2,2’-dithio diethanol (SS-DOH), and random copolymerization of MEO2MA and OEGMA monomers via atom transfer radical polymerization (ATRP) technology. The chemical structures and compositions of the novel copolymers were demonstrated by proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR). The molecular weights of the novel copolymers were measured by size exclusive chromatography (SEC) and proved to have a relatively narrow molecular weight distribution coefficient (ÐM ≤ 1.50). The water solubility and transmittance of the novel copolymers were tested via visual observation and UV–Vis spectroscopy, which proved the SPMO had a good hydrophilicity and suitable low critical solution temperature (LCST). The critical micelle concentration (CMC) of the novel polymeric micelles were determined using surface tension method and fluorescent probe technology. The particle size and morphology of the novel polymeric micelles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The sol–gel transition behavior of the novel copolymers was studied via vial flip experiments. Finally, the hydrophobic anticancer drug doxorubicin (DOX) was used to study the in vitro release behavior of the novel drug-loaded micelles. The results show that the novel polymeric micelles are expected to become a favorable drug carrier. In addition, they exhibit reductive responsiveness to the small molecule reducing agent dithiothreitol (DTT) and temperature responsiveness with temperature changes.

Highlights

In recent years, amphiphilic copolymers have drawn much attention in the field of biomedicine due to their small size and loading capacity of hydrophobic drugs
Temperature/reduction dual-stimulus responsive triblock copolymers were synthesized with different different polymerization (DP) by atom transfer radical polymerization (ATRP) technology with iBuBr-PLLA-SS-PLLA-iBuBr as the macromolecular initiator and MEO2 MA and oligo(ethylene glycol) methacrylate (OEGMA) as the monomers for polymerization
It shows that the SPMO polymeric micelles have relatively low Critical Micelle Concentration (CMC), so the micelles can exist stably as a drug carrier for a long time in the human body to achieve the effect of sustained indicates that the CMC of SPMO1, SPMO2, and SPMO3 measured are 0.005 mg/mL, 0.0075 mg/mL, and 0.0147 mg/mL, respectively, by fluorescent probe technology. It shows that the SPMO polymeric micelles have relatively low CMC, so the micelles can exist stably as a drug carrier for a long time in the human body to achieve the effect of sustained drug release; on the other hand, it is proved that the DP of the hydrophilic segments can affect the CMC of the micelles

Summary

Introduction

Amphiphilic copolymers have drawn much attention in the field of biomedicine due to their small size and loading capacity of hydrophobic drugs. They can be used as the carrier for targeted drug delivery or the delivery tools for cancer chemotherapeutics. In the past few decades, single-stimulus-responsive copolymers have been widely developed, and multi-stimulus-responsive copolymers molecules are gradually designed because of their responding to each stimulus environment accurately and independently. They can co-regulate the drug release behavior under multiple stimuli [12]. It is very meaningful to design a unique copolymer molecule with multiple stimulus responsiveness

Methods

Results

Conclusion