Thermosensitive behavior of poly(ethylene glycol)/poly(2‐(N,N‐dimethylamino)ethyl methacrylate) double hydrophilic block copolymers

The poly(ethylene glycol)/poly(2‐(N,N‐dimethylamino)ethyl methacrylate) (PEG/PDMAEMA) double hydrophilic block copolymers were synthesized by atom transfer radical polymerization using mPEG‐Br or Br‐PEG‐Br as macroinitiators. The narrow molecular weight distribution of PEG/PDMAEMA block copolymers was identified by gel permeation chromatography results. The thermosensitivity of PEG/PDMAEMA block copolymers in aqueous solution was revealed to depend significantly on pH, ionic strength, chain structure, and concentration of the block copolymers. By optimizing these factors, the cloud point temperature of PEG/PDMAEMA block copolymers can be limited within body temperature range (30–37 °C), which suggests that PEG/PDMAEMA block copolymers could be a good candidate for drug delivery systems. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 503–508, 2010     

Synthesis and self‐assembly of stimuli‐responsive amphiphilic block copolymers based on polyhedral oligomeric silsesquioxane

A novel POSS‐containing methacrylate monomer (HEMAPOSS) was fabricated by extending the side chain between polyhedral oligomeric silsesquioxane (POSS) unit and methacrylate group, which can efficiently decrease the steric hindrance in free‐radical polymerization of POSS‐methacrylate monomer. POSS‐containing homopolymers (PHEMAPOSS) with a higher degree of polymerization (DP) can be prepared using HEMAPOSS monomer via reversible addition–fragmentation chain transfer (RAFT) polymerization. PHEMAPOSS was further used as the macro‐RAFT agent to construct a series of amphiphilic POSS‐containing poly(N, N‐dimethylaminoethyl methacrylate) diblock copolymers, PHEMAPOSS‐b‐PDMAEMA. PHEMAPOSS‐b‐PDMAEMA block copolymers can self‐assemble into a plethora of morphologies ranging from irregular assembled aggregates to core‐shell spheres and further from complex spheres (pearl‐necklace‐liked structure) to large compound vesicles. The thermo‐ and pH‐responsive behaviors of the micelles were also investigated by dynamic laser scattering, UV spectroscopy, SEM, and TEM. The results reveal the reversible transition of the assembled morphologies from spherical micelles to complex micelles was realized through acid‐base control. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2669‐2683     

Poly(dimethylaminoethyl methacrylate)‐b‐poly(hydroxypropyl methacrylate) copolymers: Synthesis and pH/thermo‐responsive behavior in aqueous solutions

The synthesis and self‐assembly properties in aqueous solutions of novel amphiphilic block copolymers composed of one hydrophilic, pH and temperature responsive poly(dimethyl amino ethyl methacrylate) (PDMAEMA) block and one weakly hydrophobic, water insoluble, potentially thermoresponsive poly(hydroxy propyl methacrylate) (PHPMA) block, are reported. The block copolymers were prepared by RAFT polymerization and were molecularly characterized by size exclusion chromatography, NMR, and FTIR spectroscopies. The PDMAEMA‐b‐PHPMA amphiphilic block copolymers self‐assemble in different nanostructured aggregates when inserted in aqueous media. The effects of different solubilization protocols, as well as the effects of solution temperature and pH on the structure of the aggregates, are studied by light scattering and fluorescence spectroscopy measurements. Experimental results indicate that there is a number of solution preparation and physicochemical parameters that allow the control and manipulation of the structure and thermoresponsive properties of PDMAEMA‐b‐PHPMA aggregates in aqueous media. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1962–1977     

Cyclodextrin‐overhanging hyperbranched core‐double‐shell miktoarm architectures: Synthesis and gradient stimuli‐responsive properties

We report the synthesis and gradient stimuli‐responsive properties of cyclodextrin‐overhanging hyperbranched core‐double‐shell miktoarm architectures. A ionic hyperbranched poly(β‐cyclodextrin) (β‐CD) core was firstly synthesized via a convenient “A₂+B₃” approach. Double‐layered shell architectures, composed of poly(N‐isopropyl acrylamide) (PNIPAm) and poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA) miktoarms as the outermost shell linked to poly(N,N‐diethylaminoethyl methacrylate) (PDEAEMA) homoarms which form the inner shell, were obtained by a sequential atom transfer radical polymerization (ATRP) and parallel click chemistry from the modified hyperbranched poly(β‐CD) macroinitiator. The combined characterization by ¹H NMR, ¹³C NMR, ¹H‐²⁹Si heteronuclear multiple‐bond correlation (HMBC), FTIR and size exclusion chromatography/multiangle laser light scattering (SEC/MALLS) confirms the remarkable hyperbranched poly(β‐CD) core and double‐shell miktoarm architectures. The gradient triple‐stimuli‐responsive properties of hyperbranched core‐double‐shell miktoarm architectures and the corresponding mechanisms were investigated by UV–vis spectrophotometer and dynamic light scattering (DLS). Results show that this polymer possesses three‐stage phase transition behaviors. The first‐stage phase transition comes from the deprotonation of PDEAEMA segments at pH 9–10 aqueous solution under room temperature. The confined coil‐globule conformation transition of PNIPAm and PDMAEMA arms gives rise to the second‐stage hysteretic cophase transition between 38 and 44 °C at pH 10. The third‐stage phase transition occurs above 44 °C at pH = 10 attributed to the confined secondary conformation transition of partial PDMAEMA segments. This cyclodextrin‐overhanging hyperbranched core‐double‐shell miktoarm architectures are expected to solve the problems of inadequate functionalities from core layer and lacking multiresponsiveness for shell layers existing in the dendritic core‐multishell architectures. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Dual‐responsive copolymer poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate)‐block‐poly[2‐(dimethylamino)ethyl methacrylate] synthesized via photoATRP for surface with tunable wettability

In this work, a series of block copolymers of poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate)‐block‐poly[2‐(dimethylamino)ethyl methacrylate] (PHFBMA‐b‐PDMAEMA) were synthesized via photo‐induced atom transfer radical polymerization (photoATRP) at room temperature. By the introduction of PDMAEMA segment, the hydrophilicity of the silicon wafer surface spin‐coated with PHFBMA homopolymer was improved. Furthermore, the study of tunable surface wettability showed that the surface wettability was pH‐dependent and thermal‐independent at pH 2 and 10. The as‐fabricated surface coated with PHFBMA₁₁₀‐b‐PDMAEMA₁₈₇ showed switchable water contact angle from 85.4° at pH > 4 to 55.0° at pH 2 due to the protonation and deprotonation of tertiary amine groups of PDMAEMA. However, because of the ascendancy of protonated PDMAEMA at pH 2 and the decreased LCST at pH 10, the wettability of the as‐prepared surfaces was thermal‐insensitive. Finally, surface morphology and composition investigation showed that the property of wettability‐controllable surface was not only influenced by surface composition, but also affected by chain conformation. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3868–3877     

Stimuli‐responsive amphiphilic PDMAEMA‐b‐PLMA copolymers and their cationic and zwitterionic analogs

In this work, the synthesis and characterization of novel amphiphilic diblock copolymers of poly(2‐dimethylamino ethyl methacrylate)‐b‐poly(lauryl methacrylate), PDMAEMA‐b‐PLMA, using the reversible addition‐fragmentation chain transfer (RAFT) polymerization technique, are reported. The diblocks were successfully derivatized to cationic and zwitterionic block polyelectrolytes by quaternization and sulfobetainization of the PDMAEMA block, respectively. Furthermore, their molecular and physicochemical characterization was performed by using characterization techniques such as NMR and FTIR, size exclusion chromatography, light scattering techniques, and transmission electron microscopy. The structure of the diblock micelles, their behavior, and properties in aqueous solution were investigated under the effect of pH, temperature, and ionic strength, as PDMAEMA and its derivatives are stimuli‐responsive polymers and exhibit responses to variations of at least one of these physicochemical parameters. These new families of stimuli‐responsive block copolymers respond to changes of their environment giving interesting nanostructures, behavioral motifs, and properties, rendering them useful as nanocarriers for drug delivery and gene therapy. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 598–610     

Multi‐stimuli‐responsive self‐immolative polymer assemblies

Self‐immolative polymers (SIPs) undergo depolymerization in response to the cleavage of stimuli‐responsive end‐caps from their termini. Some classes of SIPs, including polycarbamates, have depolymerization rates that depend on environmental factors such as solvent and pH. In previous work, hydrophobic SIPs have been incorporated into amphiphilic block copolymers and used to prepare nanoassemblies. However, stimuli‐responsive hydrophilic blocks have not previously been incorporated. In this work, we synthesized amphiphilic copolymers composed of a hydrophobic polycarbamate SIP block and a hydrophilic poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) block connected by a UV light‐responsive linker end‐cap. It was hypothesized that after assembly of the block copolymers into nanoparticles, chain collapse of the PDMAEMA above its lower critical solution temperature (LCST) might change the environment of the SIP block, thereby altering its depolymerization rate. Self‐assembly of the block copolymers was performed, and the depolymerization of the resulting assemblies was studied by fluorescence spectroscopy, dynamic light scattering, and NMR spectroscopy. At 20 °C, the system exhibited a selective response to the UV light. At 65 °C, above the LCST of PDMAEMA, the systems underwent more rapid depolymerization, suggesting that the increase in rate arising from the higher temperature dominated over environmental effects arising from chain collapse. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1868–1877     

Synthesis and characterization of double thermo‐responsive block copolymer consisting N‐isopropylacrylamide by atom transfer radical polymerization

In this thesis, we studied the convenient synthesis and characterizations of thermo‐responsive materials with double response. To achieve these, AB‐type diblock copolymers comprising of poly(N‐isopropylacrylamide) (NIPAAm) segment and poly(NIPAAm‐co‐(N‐(hydroxymethyl)acrylamide) (HMAAm)) one were designed. That was synthesized in one‐pot using an atom transfer radical polymerization (ATRP) technique. Poly(NIPAAm‐co‐HMAAm)s synthesized separately showed sensitive thermo‐response and the cloud point was completely tunable by the composition of HMAAm. As expected, the block copolymers exhibited double thermo‐responsive profiles in aqueous solution. The responsive behavior was discussed by precise trace by ¹H NMR and turbidity measurements. From these results, we could confirm almost independent dehydration of each segment. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6142–6150, 2008     

Dual thermo‐ and pH‐sensitive network‐grafted hydrogels formed by macrocrosslinker as drug delivery system

Dual thermo‐ and pH‐sensitive network‐grafted hydrogels made of poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA) network and poly(N‐isopropylacrylamide) (PNIPAM) grafting chains were successfully synthesized by the combination of atom transfer radical polymerization (ATRP), reversible addition‐fragmentation chain transfer (RAFT) polymerization, and click chemistry. PNIPAM having two azide groups at one chain end [PNIPAM‐(N₃)₂] was prepared with an azide‐capped ATRP initiator of N,N‐di(β‐azidoethyl) 2‐chloropropionylamide. Alkyne‐pending poly(N,N‐dimethylaminoethyl methacrylate‐co‐propargyl acrylate) [P(DMAEMA‐co‐ProA)] was obtained through RAFT copolymerization using dibenzyltrithiocarbonate as chain transfer agent. The subsequent click reaction led to the formation of the network‐grafted hydrogels. The influences of the chemical composition of P(DMAEMA‐co‐ProA) on the properties of the hydrogels were investigated in terms of morphology and swelling/deswelling kinetics. The dual stimulus‐sensitive hydrogels exhibited fast response, high swelling ratio, and reproducible swelling/deswelling cycles under different temperatures and pH values. The uptake and release of ceftriaxone sodium by these hydrogels showed both thermal and pH dependence, suggesting the feasibility of these hydrogels as thermo‐ and pH‐dependent drug release devices. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Polyisobutylene‐b‐Poly(N,N‐diethylacrylamide) well‐defined amphiphilic diblock copolymer: Synthesis and thermo‐responsive phase behavior

Polyisobutylene‐b‐poly(N,N‐diethylacrylamide) (PIB‐b‐PDEAAm) well‐defined amphiphilic diblock copolymers were synthesized by sequential living carbocationic polymerization and reversible addition‐fragmentation chain transfer (RAFT) polymerization. The hydrophobic polyisobutylene segment was first built by living carbocationic polymerization of isobutylene at ?70 ° C followed by multistep transformations to give a well‐defined (M_w/M_n = 1.22) macromolecular chain transfer agent, PIB‐CTA. The hydrophilic poly(N,N‐diethylacrylamide) block was constructed by PIB‐CTA mediated RAFT polymerization of N,N‐diethylacrylamide at 60 ° C to afford the desired well‐defined PIB‐b‐PDEAAm diblock copolymers with narrow molecular weight distributions (M_w/M_n ≤1.26). Fluorescence spectroscopy, transmission electron microscope, and dynamic light scattering (DLS) were employed to investigate the self‐assembly behavior of PIB‐b‐PDEAAm amphiphilic diblock copolymers in aqueous media. These diblock copolymers also exhibited thermo‐responsive phase behavior, which was confirmed by UV‐Vis and DLS measurements. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1143–1150     

pH‐ and temperature‐sensitive statistical copolymers poly[2‐(dimethylamino)ethyl methacrylate‐stat‐2‐vinylpyridine] with Functional succinimidyl‐ester chain ends synthesized by nitroxide‐mediated polymerization

Statistical copolymerizations of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) with 2‐vinylpyridine (2VP) with 80 to 99 mol % DMAEMA in the feed utilizing a succinimidyl ester‐terminated alkoxyamine unimolecular initiator (NHS‐BlocBuilder) at 80 °C in bulk were performed. The effectiveness of 2VP as a controlling comonomer is demonstrated by linear increases in number‐average molecular weight versus conversion, relatively low PDI (1.5–1.6 with up to 98% DMAEMA) and successful chain extensions with 2VP. Additional free nitroxide does not significantly improve control for the DMAEMA/2VP copolymerizations. The succinimidyl ester on the initiator permits coupling to amine‐terminated poly(propylene glycol) (PPG), yielding an effective macroinitiator for synthesizing a doubly thermo‐responsive block copolymer of PPG‐block‐P(DMAEMA/2VP). A detailed study of the thermo‐ and pH‐sensitivities of the statistical and block copolymers is also presented. The cloud point temperature of the statistical copolymers is fine tuned from 14 to 75 °C by varying polymer composition and pH. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012.     

Single‐step process to produce functionalized multiresponsive polymeric particles

Monodisperse functional multiresponsive particles were prepared by encapsulation of an amphiphilic diblock copolymer during the precipitation polymerization of polystyrene and divinylbenzene in one single step. The amphiphilic diblock copolymer employed throughout this study, polystyrene‐b‐poly (dimethylaminoethyl methacrylate) (PS‐b‐PDMAEMA) has been synthesized by ATRP in two consecutive polymerization steps. After encapsulation of the block copolymer within the microsphere, the surface modification of the particle occurs spontaneously upon exposure to water by surface segregation of the hydrophilic PDMAEMA block, thus without any additional post‐polymerization and/or chemical modification steps. The response of the functionalized particles both to pH and temperature was analyzed by potential zeta and DSC measurements. Upon dispersion of the particles in acidic media, the PDMAEMA block in its charged state is soluble and does not exhibit any change by heating. At higher pH values and temperatures above 35 °C (Low Critical Solubility Temperature of the PDMAEMA block) the hydrophilic segment collapses as detected by differential scanning calorimetry. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3523–3533, 2010     

A new thermo‐responsive block copolymer with tunable upper critical solution temperature and lower critical solution temperature in the alcohol/water mixture

The multi‐thermo‐responsive block copolymer of poly[2‐(2‐methoxyethoxy)ethyl methacrylate]‐block‐poly[N‐(4‐vinylbenzyl)‐N,N‐diethylamine] (PMEO₂MA‐b‐PVEA) displaying phase transition at both the lower critical solution temperature (LCST) and the upper critical solution temperature (UCST) in the alcohol/water mixture is synthesized by reversible addition‐fragmentation chain transfer polymerization. The poly[2‐(2‐methoxyethoxy)ethyl methacrylate] (PMEO₂MA) block exhibits the UCST phase transition in alcohol and the LCST phase transition in water, while the poly[N‐(4‐vinylbenzyl)‐N,N‐diethylamine] (PVEA) block shows the UCST phase transition in isopropanol and the LCST phase transition in the alcohol/water mixture. Both the polymer molecular weight and the co‐solvent/nonsolvent exert great influence on the LCST or UCST of the block copolymer. By adjusting the solvent character including the water content and the temperature, the block copolymer undergoes multiphase transition at LCST or UCST, and various block copolymer morphologies including inverted micelles, core‐corona micelles, and corona‐collapsed micelles are prepared. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4399–4412     

Dual‐responsive supramolecular inclusion complexes of block copolymer poly(ethylene glycol)‐block‐poly[(2‐dimethylamino)ethyl methacrylate] with α‐cyclodextrin

A new class of temperature and pH dual‐responsive and injectable supramolecular hydrogel was developed, which was formed from block copolymer poly(ethylene glycol)‐block‐poly[(2‐dimethylamino)ethyl methacrylate] (PEG‐b‐PDMAEMA) and α‐cyclodextrin (α‐CD) inclusion complexes (ICs). The PEG‐b‐PDMAEMA diblock copolymers with different ratio of ethylene glycol (EG) to (2‐dimethylamino)ethyl methacrylate (DMAEMA) (102:46 and 102:96, respectively) were prepared by atom transfer radical polymerization (ATRP). ¹H NMR measurement indicated that the ratio of EG unit to α‐CD in the resulted ICs was higher than 2:1. Thermal analysis showed that thermal stability of ICs was improved. The rheology studies showed that the hydrogels were temperature and pH sensitive. Moreover, the hydrogels were thixotropic and reversible. The self‐assembly morphologies of the ICs in different pH and ionic strength environment were studied by transmission electron microscopy. The formed biocompatible micelles have potential applications as biomedical and stimulus‐responsive material. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2143–2153, 2010     

Crystallization and stereocomplexation behavior of poly(D‐ and L‐lactide)‐b‐poly(N,N‐dimethylamino‐2‐ethyl methacrylate) block copolymers

The thermal properties, crystallization, and morphology of amphiphilic poly(D ‐lactide)‐b‐poly(N,N‐dimethylamino‐2‐ethyl methacrylate) (PDLA‐b‐PDMAEMA) and poly (L ‐lactide)‐b‐poly(N,N‐dimethylamino‐2‐ethyl methacrylate) (PLLA‐b‐PDMAEMA) copolymers were studied and compared to those of the corresponding poly(lactide) homopolymers. Additionally, stereocomplexation of these copolymers was studied. The crystallization kinetics of the PLA blocks was retarded by the presence of the PDMAEMA block. The studied copolymers were found to be miscible in the melt and the glassy state. The Avrami theory was able to predict the entire crystallization range of the PLA isothermal overall crystallization. The melting points of PLDA/PLLA and PLA/PLA‐b‐PDMAEMA stereocomplexes were higher than those formed by copolymer mixtures. This indicates that the PDMAEMA block is influencing the stability of the stereocomplex structures. For the low molecular weight samples, the stereocomplexes particles exhibited a conventional disk‐shape structure and, for high molecular weight samples, the particles displayed unusual star‐like shape morphology. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1397–1409, 2011     

Influence of the polymer structure over self‐assembly and thermo‐responsive properties: The case of PEG‐b‐PCL grafted copolymers via a combination of RAFT and ROP

During the last years, the field of drug delivery has experienced a growing interest toward the so‐called thermo‐responsive polymers: synthetic materials that, due to the specific hydrophilic–lipophilic balance of their repeating units, exhibit a lower critical solution temperature (LCST) in water associated to a characteristic coil–globule transition. In this work, thermo‐responsive amphiphilic block copolymers are synthesized via reversible addition‐fragmentation transfer (RAFT) polymerization starting from thermo‐responsive monomers and a hydrophobic biodegradable macromonomer, oligo(caprolactone)methacrylate (CL₃MA), produced via ring opening polymerization (ROP). The obtained copolymers exhibit an interesting self‐assembly behavior leading to nanoparticles (NPs) as long as temperature is kept below the LCST. Otherwise, once this value is overcome, the destabilization of the NPs causes the formation of hydrophobic superstructures that enhance the release of an entrapped lipophilic drug. This characteristic behavior has been systematically studied and related to the copolymer structure. In particular, the self‐assembly behavior as well as temperature‐triggered NP destabilization have been related to the relative length of the two blocks constituting the copolymers and to their hydrophilic–lipophilic balance (HLB). Finally, the efficacy of the thermo‐responsive triggered drug release has been tested in the case of Paclitaxel (PTX). © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2919–2931     

Well‐defined poly[(dimethylamimo)ethyl methacrylate]‐b‐poly(fluoroalkyl methacrylate) diblock copolymers: Effects of different fluoroalkyl groups on the solution properties

A series of well‐defined, fluorinated diblock copolymers, poly[2‐(dimethylamino)ethyl methacrylate]‐b‐poly(2,2,2‐trifluoroethyl methacrylate) (PDMA‐b‐PTFMA), poly[2‐(dimethylamino)ethyl methacrylate]‐b‐poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate) (PDMA‐b‐PHFMA), and poly[2‐(dimethylamino)ethyl methacrylate]‐b‐poly(2,2,3,3,4,4,5,5‐octafluoropentyl methacrylate) (PDMA‐b‐POFMA), have been synthesized successfully via oxyanion‐initiated polymerization. Potassium benzyl alcoholate (BzO^?K⁺) was used to initiate DMA monomer to yield the first block PDMA. If not quenched, the first living chain could be subsequently used to initiate a feed F‐monomer (such as TFMA, HFMA, or OFMA) to produce diblock copolymers containing different poly(fluoroalkyl methacrylate) moieties. The composition and chemical structure of these fluorinated copolymers were confirmed by ¹H NMR, ¹⁹F NMR spectroscopy, and gel permeation chromatography (GPC) techniques. The solution behaviors of these copolymers containing (tri‐, hexa‐, or octa‐ F‐atom)FMA were investigated by the measurements of surface tension, dynamic light scattering (DLS), and UV spectrophotometer. The results indicate that these fluorinated copolymers possess relatively high surface activity, especially at neutral media. Moreover, the DLS and UV measurements showed that these fluorinated diblock copolymers possess distinct pH/temperature‐responsive properties, depending not only on the PDMA segment but also on the fluoroalkyl structure of the FMA units. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2702–2712, 2009     

Synthesis and supramolecular self‐assembly of thermosensitive amphiphilic star copolymers based on a hyperbranched polyether core

A novel amphiphilic thermosensitive star copolymer with a hydrophobic hyperbranched poly (3‐ethyl‐3‐(hydroxymethyl)oxetane) (HBPO) core and many hydrophilic poly(2‐(dimethylamino) ethyl methacrylate) (PDMAEMA) arms was synthesized and used as the precursor for the aqueous solution self‐assembly. All the copolymers directly aggregated into core–shell unimolecular micelles (around 10 nm) and size‐controllable large multimolecular micelles (around 100 nm) in water at room temperature, according to pyrene probe fluorescence spectrometry and ¹H NMR, TEM, and DLS measurements. The star copolymers also underwent sharp, thermosensitive phase transitions at a lower critical solution temperature (LCST), which were proved to be originated from the secondary aggregation of the large micelles driven by increasing hydrophobic interaction due to the dehydration of PDMAEMA shells on heating. A quantitative variable temperature NMR analysis method was designed by using potassium hydrogen phthalate as an external standard and displayed great potential to evaluate the LCST transition at the molecular level. The drug loading and temperature‐dependent release properties of HBPO‐star‐PDMAEMA micelles were also investigated by using indomethacin as a model drug. The indomethacin‐loaded micelles displayed a rapid drug release at a temperature around LCST. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 668–681, 2008     

Synthesis and Self‐Assembly of pH‐Responsive Amphiphilic Poly(dimethylaminoethyl methacrylate)‐block‐Poly(pentafluorostyrene) Block Copolymer in Aqueous Solution

We report the synthesis of a novel pH‐responsive amphiphilic block copolymer poly(dimethylaminoethyl methacrylate)‐block‐poly(pentafluorostyrene) (PDMAEMA‐b‐PPFS) using RAFT‐mediated living radical polymerization. Copolymer micelle formation, in aqueous solution, was investigated using fluorescence spectroscopy, static and dynamic light scattering (SLS and DLS), and transmission electron microscopy (TEM). DLS and SLS measurements revealed that the diblock copolymers form spherical micelles with large aggregation numbers, N_agg ≈ 30 where the dense PPFS core is surrounded by dangling PDMAEMA chains as the micelle corona. The hydrodynamic radii, R_h of these micelles is large, at pH 2–5 as the protonated PDMAEMA segments swell the micelle corona. Above pH 5, the PDMAEMA segments are gradually deprotonated, resulting in a lower osmotic pressure and enhanced hydrophobicity within the micelle, thus decreasing the R_h. However, the radius of gyration, R_g remains independent of pH as the dense PPFS cores predominate.

     

Hydrophobically controlled self‐association of pH‐ and thermo‐sensitive triblock copolymers based on poly(acrylic acid‐co‐tert‐butyl acrylate) and poly(propylene oxide)

Aqueous solution properties of amphiphilic P(AA‐co‐tBA)‐b‐PPO‐b‐ P(AA‐co‐tBA) copolymers having various tBA contents are presented in this article. These copolymers show pH‐sensitive behavior depending on tBA/AA ratio. Hydrophobic interactions between tBA units leading to pH‐dependent macroscopic aggregates were evidenced by turbidimetry. The aggregation behavior of the PPO middle block was concealed in presence of tBA units. The formation of water‐soluble aggregated objects was characterized by Asymmetrical Flow Field Flow Fractionation (AsF4). By increasing tBA/AA ratio, we observed an increase of aggregates size as well as a reduction of the critical concentration aggregation. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1944–1949