Morphology and temperature responsiveness–swelling relationship of poly(N‐isopropylamide–chitosan) copolymers and their application to drug release

Poly [N‐isopropylacrylamide (NIPAAm)–chitosan] crosslinked copolymer particles were synthesized by soapless emulsion copolymerization of NIPAAm and chitosan. An anionic initiator [ammonium persulfate (APS)] and a cationic initiator [2,2′‐azobis(2‐methylpropionamidine)dihydrochloride (AIBA)] were used to initiate the reaction of copolymerization. The chitosan–NIPAAm copolymer synthesized by using APS as the initiator showed a homogeneous morphology and exhibited the characteristic of a lower critical solution temperature (LCST). The copolymer synthesized by using AIBA as an initiator showed a core–shell morphology, and the characteristic of LCST was insignificant. The LCST of the chitosan–NIPAAm copolymer depended on the morphology of the copolymer particles. In addition, the chitosan–NIPAAm copolymer particles were processed to form copolymer disks. Then, the effect of various variables such as the chitosan/NIPAAm weight ratio, the concentration of crosslinking agent, and the pH values on the swelling ratio of chitosan–NIPAAm copolymer disks were investigated. Furthermore, caffeine was used as the model drug to study the characteristics of drug loading of the chitosan–NIPAAm copolymer disks. Variables such as the chitosan/NIPAAm weight ratio and the concentration of the crosslinking agent significantly influenced the behavior of caffeine loading. Two factors (pore size and swelling ratio) affected the behavior of caffeine release from the chitosan–NIPAAm copolymer disks. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3029–3037, 2004     

Synthesis and characteristics of poly(methacrylic acid‐co‐N‐isopropylacrylamide) thermosensitive composite hollow latex particles and their application as drug carriers

In this work, the poly(methacrylic acid‐co‐N‐isopropylacrylamide) thermosensitive composite hollow latex particles was synthesized by a three‐step reaction. The first step was to synthesize the poly(methyl methacrylate‐co‐methacrylic acid) (poly(MMA‐MAA)) copolymer latex particles by the method of soapless emulsion polymerization. The second step was to polymerize methacrylic acid (MAA), N‐isopropylacrylamide (NIPAAm), and N,N′‐methylenebisacrylamide in the presence of poly(MMA‐MAA) latex particles to form the linear poly(methyl methacrylate‐co‐methacrylic acid)/crosslinking poly(methacrylic acid‐co‐N‐isopropylacrylamide) (poly(MMA‐MAA)/poly(MAA‐NIPAAm)) core–shell latex particles. In the third step, the core–shell latex particles were heated in the presence of ammonia solution to form the crosslinking poly(MAA‐NIPAAm) thermosensitive hollow latex particles. The morphologies of poly(MMA‐MAA)/poly(MAA‐NIPAAm) core–shell latex particles and poly(MAA‐NIPAAm) hollow latex particles were observed. The influences of crosslinking agent and shell composition on the lower critical solution temperature of poly(MMA‐MAA)/poly(MAA‐NIPAAm) core–shell latex particles and poly(MAA‐NIPAAm) hollow latex particles were, respectively, studied. Besides, the poly(MAA‐NIPAAm) thermosensitive hollow latex particles were used as carriers to load with the model drug, caffeine. The effect of various variables on the amount of caffeine loading and the efficiency of caffeine release was investigated. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5203–5214     

Synthesis and characteristics of poly(methyl methacrylate‐co‐methacrylic acid)/poly(methacrylic acid‐co‐N‐isopropylacrylamide) thermosensitive semi‐hollow latex particles and their application to drug carriers

In this work, the poly(methyl methacrylate‐co‐methacrylic acid)/poly(methacrylic acid‐co‐N‐isopropylacrylamide) thermosensitive composite semi‐hollow latex particles was synthesized by three processes. The first process was to synthesize the poly(methyl methacrylate‐co‐methacrylic acid) (poly (MMA‐MAA)) copolymer latex particles by the method of soapless emulsion polymerization. The second process was to polymerize methacrylic acid (MAA), N‐isopropylacrylamide (NIPAAm), and crosslinking agent, N,N′‐methylenebisacrylamide, in the presence of poly(MMA‐MAA) latex particles to form the linear poly(methyl methacrylate‐co‐methacrylic acid)/crosslinking poly(methacrylic acid‐co‐N‐isopropylacrylamide) (poly(MMA‐MAA)/poly(MAA‐NIPAAm)) core–shell latex particles with solid structure. In the third process, part of the linear poly(MMA‐MAA) core of core–shell latex particles was dissolved by ammonia to form the poly(MMA‐MAA)/poly(MAA‐NIPAAm) thermosensitive semi‐hollow latex particles. The morphologies of the semi‐hollow latex particles show that there is a hollow zone between the linear poly(MMA‐MAA) core and the crosslinked poly(MAA‐NIPAAm) shell. The crosslinking agent and shell composition significantly influenced the lower critical solution temperature of poly(MMA‐MAA)/poly(MAA‐NIPAAm) semi‐hollow latex particles. Besides, the poly(MMA‐MAA)/poly(MAA‐NIPAAm) thermosensitive semi‐hollow latex particles were used as carriers to load with the model drug, caffeine. The processes of caffeine loaded into the semi‐hollow latex particles appeared four situations, which was different from that of solid latex particles. In addition, the phenomenon of caffeine released from the semi‐hollow latex particles was obviously different from that of solid latex particles. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3441–3451     

Polypyrrole/poly(N‐isopropylacrylamide‐co‐acrylic acid) thermosensitive and electrically conductive composite microgels

The electrically conductive polypyrrole/dodecylbenzene sulfonic acid/poly(N‐isopropylacrylamide‐co‐acrylic acid) (PPy/DBSA/poly(NIPAAm‐co‐AA)) composite microgels were synthesized by a chemical oxidation of pyrrole in the presence of DBSA as the primary dopant, and poly(NIPAAm‐co‐AA) microgels as the polymeric codopant and template, in which APS was used as the oxidant. It was proposed to prepare “intelligent” polymer microgel particles containing both thermosensitive and electrically conducting properties. The polymerization of pyrrole took place directly inside the microgel networks, leading to formation of composite microgels and the morphology was observed by transmission electron microscope. PPy particles interacted strongly with microgels, as the acid groups of microgels acted as the polymeric codopant. The composite microgels thus formed showed electrically conducting behavior dependent on humidity and temperature. At temperatures lower than lower critical solution temperature, the conductivity decreased with increasing the humidity and a small hysteresis phenomenon was observed. The hysteresis became indistinct when temperature was near volume phase transition temperature. However, after the treatment of high temperature and high humidity, the conductivity increased surprisingly due to the structure reorganization inside the composite microgels. The distinctive functionality of the PPy composite microgels was expected to be utilized in many attractive applications. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1648–1659, 2006     

Synthesis and characteristics of poly(N‐isopropylacrylamide‐co‐methacrylic acid)/Fe3O4/poly(N‐isopropylacrylamide‐co‐methacrylic acid) two‐shell thermosensitive magnetic composite hollow latex particles

In this study, the poly(N‐isopropylacrylamide‐methylacrylate acid)/Fe₃O₄/poly(N‐isopropylacrylamide‐methylacrylate acid) (poly(NIPAAm‐MAA)/Fe₃O₄/poly(NIPAAm‐MAA)) two‐shell magnetic composite hollow latex particles were synthesized by four steps. The poly(methyl methacrylate‐co‐methylacrylate acid) (poly(MMA‐MAA)) copolymer latex particles were synthesized first. Then, the second step was to polymerize NIPAAm, MAA, and crosslinking agent in the presence of poly(MMA‐MAA) latex particles to form the linear poly(MMA‐MAA)/crosslinking poly(NIPAAm‐MAA) core–shell latex particles. Then, the core–shell latex particles were heated in the presence of NH₄OH to dissolve the linear poly(MMA‐MAA) core to form the poly(NIPAAm‐MAA) hollow latex particles. In the third step, the Fe₃O₄ nanoparticles were generated in the presence of poly(NIPAAm‐MAA) hollow polymer latex particles and formed the poly(NIPAAm‐MAA)/Fe₃O₄ magnetic composite hollow latex particles. The fourth step was to synthesize poly(NIPAAm‐MAA) in the presence of poly(NIPAAm‐MAA)/Fe₃O₄ latex particles to form the poly(NIPAAm‐MAA)/Fe₃O₄/poly(NIPAAm‐MAA) two‐shell magnetic composite hollow latex particles. The effect of various variables such as reactant concentration, monomer ratio, and pH value on the morphology and volume‐phase transition temperature of two‐shell magnetic composite hollow latex particles was studied. Moreover, the latex particles were used as carriers to load with caffeine, and the caffeine‐loading characteristics and caffeine release rate of latex particles were also studied. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2880–2891     

Preparation,morphology, and thermoresponsive properties of poly(N‐isopropylacrylamide)‐based copolymer microgels

In this research, thermoresponsive copolymer latex particles with an average diameter of about 200–500 nm were prepared via surfactant‐free emulsion polymerization. The thermoresponsive properties of these particles were designed by the addition of hydrophilic monomers [acrylic acid (AA) and sodium acrylate (SA)] to copolymerize with N‐isopropylacrylamide (NIPAAm). The effects of the comonomers and composition on the synthesis mechanism, kinetics, particle size, morphology, and thermoresponsive properties of the copolymer latex were also studied to determine the relationships between the synthesis conditions, the particle morphology, and the thermoresponsive properties. The results showed that the addition of hydrophilic AA or SA affected the mechanism and kinetics of polymerization. The lower critical solution temperature (LCST) of the latex copolymerized with AA rose to a higher temperature. However, because the strong hydrophilic and ionic properties of SA caused a core–shell structure, where NIPAAm was in the inner core and SA was in the outer shell, the LCST of the latex copolymerized with SA was still the same as that of pure poly(N‐isopropylacrylamide) latex. It was concluded that these submicrometer copolymer latex particles with different thermoresponsive properties could be applied in many fields. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 356–370, 2006     

Thermo‐ and pH‐induced self‐assembly of P(AA‐b‐NIPAAm‐b‐AA) triblock copolymers synthesized via RAFT polymerization

A series of environmentally sensitive ABA triblock copolymers with different block lengths were prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization from acrylic acid (AA) and N‐isopropylacrylamide (NIPAAm). The GPC and ¹H NMR analyses demonstrated the narrow molecular weight distribution and precise chemical structure of the prepared P(AA‐b‐NIPAAm‐b‐AA) triblock copolymers owing to the controlled/living characteristics of RAFT polymerization. The lower critical solution temperature (LCST) of the triblock copolymers could be tailored by adjusting the length of PAA block and controlled by the pH value. Under heating, the triblock copolymers underwent self‐assemble in dilute aqueous solution and formed nanoparticles revealed via TEM images. Physically crosslinked nanogels induced by inter‐/intra‐hydrogen bonding or core‐shell micelle particles thus could be obtained by changing environmental conditions. With a well‐defined structure and stimuli‐responsive properties, the P(AA‐b‐NIPAAm‐b‐AA) copolymer is expected to be employed as a nanocarrier for biomedical applications in controlled‐drug delivery and targeting therapy. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1109–1118     

Synthesis and characteristics of poly(N‐isopropylacrylamide‐co‐methacrylic acid)/Fe3O4 thermosensitive magnetic composite hollow latex particles

In this study, the poly(NIPAAm–MAA)/Fe₃O₄ hollow latex particles were synthesized by three steps. The first step was to synthesize the poly(methyl methacrylate‐co‐methylacrylate acid) (poly(MMA‐MAA)) copolymer latex particles by the method of soapless emulsion polymerization. Following the first step, the second step was to polymerize N‐isopropylacrylamide (NIPAAm), MAA, and crosslinking agent (N,N'‐methylene‐bisacrylamide (MBA)) in the presence of poly(MMA‐MAA) latex particles to form the linear poly(MMA‐MAA)/crosslinking poly (NIPAAm‐MAA) core‐shell latex particles. After the previous processes, the core‐shell latex particles were heated in the presence of NH₄OH to dissolve the linear poly(MMA‐MAA) core in order to form the poly(NIPAAm‐MAA) hollow latex particles. In the third step, Fe²⁺ and Fe³⁺ ions were introduced to bond with the ? COOH groups of MAA segments in the poly(NIPAAm‐MAA) hollow polymer latex particles. Further by a reaction with NH₄OH and then Fe₃O₄ nanoparticles were generated in situ and the poly(NIPAAm‐MAA)/Fe₃O₄ magnetic composite hollow latex particles were formed. The concentrations of MAA, crosslinking agent (N,N'‐methylene bisacrylamide), and Fe₃O₄ nanoparticles were important factors to influence the morphology of hollow latex particles and lower critical solution temperature of poly(NIPAAm–MAA)/Fe₃O₄ magnetic composite hollow latex particles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Novel thermo‐responsive self‐assembly micelles from a double brush‐shaped PNIPAM‐g‐(PA‐b‐PEG‐b‐PA)‐g‐PNIPAM block copolymer with PNIPAM polymers as side chains

A novel double brush‐shaped copolymer with amphiphilic polyacrylate‐b‐poly(ethylene glycol)‐b‐poly acrylate copolymer (PA‐b‐PEG‐b‐PA) as a backbone and thermosensitive poly(N‐isopropylacrylamide) (PNIPAM) long side chains at both ends of the PEG was synthesized via an atom transfer radical polymerization (ATRP) route, and the structure was confirmed by FTIR, ¹H NMR, and SEC. The thermosensitive self‐assembly behavior was examined via UV‐vis, TEM, DLS, and surface tension measurements, etc. The self‐assembled micelles, with low critical solution temperatures (LCST) of 34–38 ^°C, form irregular fusiform and/or spherical morphologies with single, double, and petaling cores in aqueous solution at room temperature, while above the LCST the micelles took on more regular and smooth spherical shapes with diameter ranges from 45 to 100 nm. The micelle exhibits high stabilities even in simulated physiological media, with low critical micellization concentration (CMC) up to 5.50, 4.89, and 5.05 mg L^?1 in aqueous solution, pH 1.4 and 7.4 PBS solutions, respectively. The TEM and DLS determination reveled that the copolymer micelle had broad size distribution below its LCST while it produces narrow and homogeneous size above the LCST. The cytotoxicity was investigated by MTT assays to elucidate the application potential of the as‐prepared block polymer brushes as drug controlled release vehicles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Thermo‐ and pH‐responsive gradient and block copolymers based on 2‐(2‐methoxyethoxy)ethyl methacrylate synthesized via atom transfer radical polymerization and the formation of thermoresponsive surfaces

A series of gradient and block copolymers, based on 2‐(2‐methoxyethoxy)ethyl methacrylate (MEO₂MA) and tert‐butyl acrylate (^tBA), were synthesized by atom transfer radical polymerization (ATRP) in a first step. The MEO₂MA monomer leads to the production of thermosensitive polymers, exhibiting lower critical solution temperature (LCST) at around room temperature, which could be adjusted by changing the proportion of ^tBA in the copolymer. In a second step, the tert‐butyl groups of ^tBA were hydrolyzed with trifluoroacetic acid to form the corresponding block and gradient copolymers of MEO₂MA and acrylic acid (AA), which exhibited both temperature and pH‐responsive behavior. These copolymers showed LCST values strongly dependent on the pH. At acid pH, a slightly decrease of LCST with an increase of AA in the copolymer was observed. However, at neutral or basic conditions, ionization of acid groups increases the hydrophilic balance considerably raising the LCST values, which even become not observable over the temperature range under study. In the last step, these carboxylic functionalized copolymers were covalently bound to biocompatible and biodegradable films of poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) [P(HB‐co‐HHx)] obtained by casting and, previously treated with ethylenediamine (ED) to render their surfaces with amino groups. Thereby, thermosensitive surfaces of modified P(HB‐co‐HHx) could be obtained. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

A simple FTIR spectroscopic method for the determination of the lower critical solution temperature of N‐isopropylacrylamide copolymers and related hydrogels

Linear and crosslinked polymers based on N‐isopropylacrylamide (NIPAAm) exhibit unusual thermal properties. Aqueous solutions of poly(N‐isopropylacrylamide) (PNIPAAm) phase‐separate upon heating above a lower critical solution temperature (LCST), whereas related hydrogels undergo a swelling–shrinking transition at an LCST. A linear copolymer made of NIPAAm/acryloxysuccinimide (98/2 mol/mol) and two hydrogels with different hydrophilicities were prepared. Fourier transform infrared (FTIR) spectroscopy was employed to determine the transition temperature and provide insights into the molecular details of the transition via probing of characteristic bands as a function of temperature. The FTIR spectroscopy method described here allowed the determination of the transition temperature for both the linear and crosslinked polymers. The transition temperatures for PNIPAAm and the gel resulting from the crosslinking with polylysine or N,N′‐methylenebisacrylamide (MBA) were in the same range, 30–35 °C. For the gels, the transition temperature increased with the hydrophilicity of the polymer matrix. The spectral changes observed at the LCST were similar for the free chains and the hydrogels, implying a similar molecular reorganization during the transition. The C H stretching region suggests that the N‐isopropyl groups and the backbone both underwent conformational changes and became more ordered upon heating above the LCST. An analysis of the amide I band suggests that the amide groups of the linear polymer were mainly involved in hydrogen bonding with water molecules below the LCST, the chain being flexible and disordered in a water solution. During the transition, around 20% of these intermolecular hydrogen bonds between the polymer and water were broken and replaced by intramolecular hydrogen bonds. Similar changes were also observed at the LCST of a gel crosslinked with MBA. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 907–915, 2000     

Synthesis strategies to incorporate acrylic acid into N‐vinylcaprolactam‐based microgels

Two different synthesis strategies were used to synthesize N‐vinylcaprolactam (VCL)‐acrylic acid (AA)‐based temperature‐ and pH‐sensitive microgels under the adequate conditions to avoid possible hydrolysis of VCL due to the presence of carboxylic groups provided by AA. Polymeric and colloidal features of the microgels were analyzed: the partial conversion evolutions of each comonomer were determined by ¹H NMR and the swelling/deswelling behavior by means of Photon Correlation Spectroscopy. Considering that microgels are porous soft nanoparticles, conductimetric titrations at the swollen state were carried out to calculate the volumetric charge density. The results indicate that the addition of AA after 30 minutes of reaction time helped to incorporate higher amounts of AA into microgels and as a result, to obtain both temperature‐ and pH‐sensitive nanoparticles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Preparation of thermosensitive membranes by radiation grafting of acrylic acid/N-isopropyl acrylamide binary mixture on PET fabric

Thermosensitive membranes were prepared by radiation-induced graft copolymerization of monomers on PET fabrics. A binary mixture of N-isopropyl acrylamide (NIPAAm) and acrylic acid (AA) was grafted on polyester fabric as a base material to introduce thermosensitive poly(N-isopropyl acrylamide) pendant chains having LCST slightly higher than 37 °C in the membrane. The influence of ferrous sulfate, radiation dose and monomer composition on the degree of grafting was studied. The structure of the grafted fabric was characterized by thermogravimetric analysis, differential scanning calorimetry and scanning electron microscopy. The thermosensitive nature of the fabric was monitored by swelling at different temperatures. The graft copolymerization of AA with NIPAAm enhanced the LCST of the resultant membrane to ∼37 °C. The moisture vapor transmission rate (MVTR) and air permeability of the fabric decreased slightly, may be due to the slight blocking of the fabric pores. The immobilization of tetracycline hydrochloride as the model drug and its release characteristics at different temperatures were monitored.     

Biodegradable thermo‐ and pH‐responsive hydrogels for oral drug delivery

In this article, novel smart hydrogels based on biodegradable pH sensitive poly(L ‐glutamic acid‐g‐2‐hydroxylethyl methacrylate) (PGH) chains and temperature‐sensitive hydroxypropylcellulose‐g‐acrylic acid (HPC‐g‐AA) segments were designed and synthesized. The influence of pH and temperature on the equilibrium swelling ratios of the hydrogels was discussed. The optical transmittance of the hydrogels was also changed as a function of temperature, which reflecting that the HPC‐g‐AA part of the hydrogels became hydrophobic at the temperature above the lower critical solution temperature (LCST). At the same time, the LCST of the hydrogels had a visible pH‐dependent behavior. Scanning electron microscopic analysis revealed the morphology of the hydrogels before and after enzymatic degradation. The biodegradation rate of the hydrogels was directly related to the PGH content and the pH value. The in vitro release of bovine serum albumin from the hydrogels were investigated. The release profiles indicated that both the HPC‐g‐AA and PGH contents played important roles in the drug release behaviors. These results show that the smart hydrogels seem to be of great promise in pH–temperature oral drug delivery systems. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

“Smart” carboxymethylchitosan hydrogels crosslinked with poly(N-isopropylacrylamide) and poly(acrylic acid) for controlled drug release

Carboxymethylchitosan (CMC) hydrogels containing thermo-responsive poly(N-isopropylacrylamide) (poly(NIPAAm)) and pH-responsive poly(acrylic acid) (poly(AA)) were prepared via a free radical polymerization in the presence of hexamethylene-1,6-di-(aminocarboxysulfonate) crosslinking agents. A proper ratio of CMC to NIPAAm and AA used in the reaction was investigated such that the thermo- and pH-responsive properties of the hydrogels were obtained. Water swelling of the hydrogels was improved when the solution pH was in basic conditions (pH 10) or the temperature was below its lower critical solution temperature (LCST). Effects of the change in solution temperature and pH on water swelling properties of the hydrogel as well as the releasing rate of an entrapped drug were also investigated. The hydrogels were not toxic and showed antibacterial activity against Straphylococcus aureus (S. aureus). The pH- and thermo-responsive properties of this novel “smart” hydrogel might be efficiently used as dual triggering mechanisms in controlled drug release applications.     

Self‐assembly of thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) micelles for drug delivery

Self‐assembled thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) (PAA‐b‐PNIPAM) micelles for entrapment and release of doxorubicin (DOX) was described. Block copolymer PAA‐b‐PNIPAM associated into core‐shell micelles in aqueous solution with collapsed PNIPAM block or protonated PAA block as the core on changing temperature or pH. Complexation of DOX with PAA‐b‐PNIPAM triggered by the electrostatic interaction and release of DOX from the complexes due to the changing of pH or temperature were studied. Complex micelles incorporated with DOX exhibited pH‐responsive and thermoresponsive drug release profile. The release of DOX from micelles was suppressed at pH 7.2 and accelerated at pH 4.0 due to the protonation of carboxyl groups. Furthermore, the cumulative release of DOX from complex micelles was enhanced around LCST ascribed to the structure deformation of the micelles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5028–5035, 2008     

Thermo‐responsive glycopolymer chains grafted onto honeycomb structured porous films via RAFT polymerization as a thermo‐dependent switcher for lectin Concanavalin a conjugation

Stable and surface‐modified films with regular porous arrays were created by crosslinking honeycomb structured porous films prepared via breath figures from poly(styrene‐co‐maleic anhydride). The formation of open or closed pores of the films was controlled by the addition of a polyion complex. Subsequent crosslinking of the films with 1,8‐diaminooctane led to films, which maintain their structure in solvents. In addition, excess amino functionality after crosslinking allowed the attachment of RAFT agent, 3‐benzylsulfanyl thiocarbonyl sulfanylpropionic acid, for the controlled surface polymerization of N‐isopropyl acrylamide (NIPAAm) and N‐acryloyl glucosamine (AGA). The attachment of thermo‐responsive glycopolymers onto the honeycomb structured porous films was confirmed using contact angle measurements and confocal fluorescence microscopy. Cleavage of surface anchored polymers via aminolysis revealed that the molecular weights of the surface grafted chains are significantly larger than the molecular weight of the chains generated in solution. The honeycomb structured porous films with their grafted PNIPAAm‐ran‐PAGA polymer chains showed selective recognition of Concanavalin A (ConA). Below the lower critical solution temperature (LCST) of the surface, the conjugation is switched off, while above the LCST the surface grafted glucose moieties bind strongly to ConA. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3440–3455, 2010     

Synthesis of a thermoresponsive shell‐crosslinked 3‐layer onion‐like polymer particle with a hyperbranched polyglycerol core

A novel thermoresponsive shell crosslinked three‐layer onion‐like polymer particles were prepared using hyperbranched polyglycerol (PG) as parents compound, the periphery hydroxyl groups of PG were transformed into trithiocarbonates (? SC(S)S? ) first; then, it was used as chain transfer agent to prepare star‐like block copolymer of N‐isopropyl acrylamide (NIPA) and N,N‐dimethylaminoethyl acrylate (DMA) in sequence via reversible addition fragmentation chain transfer (RAFT) process. Thus, a three‐layer polymer, PG? [SC(S)S? (DMA)? b? (NIPA)]_n, was obtained. The middle layer of poly(DMA) was then crosslinked with 1,8‐diiodoctane, and the resulting onion‐like three‐layer polymer showed a lower critical solution temperature (LCST) in water because of the outer layer of poly(NIPA). The LCST value only slightly depended on the crosslinking degree. Finally, the ? SC(S)S? were transformed into thiols by sequential treating with sodium borohydride and formic acid; thus, the core molecule was chemically detached from the crosslinked shell and a novel shell crosslinked polymer particle was obtained. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5652–5660, 2005     

Stimuli‐responsive diblock copolymer brushes via combination of “click chemistry” and living radical polymerization

pH‐ and temperature‐responsive poly(N‐isopropylacrylamide‐block?4‐vinylbenzoic acid) (poly(NIPAAm‐b‐VBA)) diblock copolymer brushes on silicon wafers have been successfully prepared by combining click reaction, single‐electron transfer‐living radical polymerization (SET‐LRP), and reversible addition‐fragmentation chain‐transfer (RAFT) polymerization. Azide‐terminated poly(NIPAAm) brushes were obtained by SET‐LRP followed by reaction with sodium azide. A click reaction was utilized to exchange the azide end group of a poly(NIPAAm) brushes to form a surface‐immobilized macro‐RAFT agent, which was successfully chain extended via RAFT polymerization to produce poly(NIPAAm‐b‐VBA) brushes. The addition of sacrificial initiator and/or chain‐transfer agent permitted the formation of well‐defined diblock copolymer brushes and free polymer chains in solution. The free polymer chains were isolated and used to estimate the molecular weights and polydispersity index of chains attached to the surface. Ellipsometry, contact angle measurements, grazing angle‐Fourier transform infrared spectroscopy, and X‐ray photoelectron spectroscopy were used to characterize the immobilization of initiator on the silicon wafer, poly(NIPAAm) brush formation via SET‐LRP, click reaction, and poly(NIPAAm‐b‐VBA) brush formation via RAFT polymerization. The poly(NIPAAm‐b‐VBA) brushes demonstrate stimuli‐responsive behavior with respect to pH and temperature. The swollen brush thickness of poly(NIPAAm‐b‐VBA) brush increases with increasing pH, and decreases with increasing temperature. These results can provide guidance for the design of smart materials based on copolymer brushes. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2677–2685     

Thermosensitive t‐PLA‐b‐PNIPAAm tri‐armed star block copolymer nanoscale micelles for camptothecin drug release

Thermosensitive polylactide‐block‐poly(N‐isopropylacrylamide) (t‐PLA‐b‐PNIPAAm) tri‐armed star block copolymers were synthesized by atom transfer radical polymerization (ATRP) of monomer NIPAAm using t‐PLA‐Cl as macroinitiator. The synthesis of t‐PLA‐Cl was accomplished by esterification of star polylactides (t‐PLA) with 2‐chloropropionyl chloride using trimethylolpropane as a center molecule. FT‐IR, ¹H NMR, and GPC analyses confirmed that the t‐PLA‐b‐PNIPAAm star block copolymers had well‐defined structure and controlled molecular weights. The block copolymers could form core‐shell micelle nanoparticles due to their hydrophilic‐hydrophobic trait in aqueous media, and the critical micelle concentrations (CMC) were from 6.7 to 32.9 mg L^?1, depending on the system composition. The as‐prepared micelle nanoparticles showed reversible phase changes in transmittance with temperature: transparent below low critical solution temperature (LCST) and opaque above the LCST. Transmission electron microscopy (TEM) observations revealed that the micelle nanoparticles were spherical in shape with core‐shell structure. The hydrodynamic diameters of the micelle nanoparticles depended on copolymer compositions, micelle concentrations and media. MTT assays were conducted to evaluate cytotoxicity of the camptothecin‐loaded copolymer micelles. Camptothecin drug release studies showed that the copolymer micelles exhibited thermo‐triggered targeting drug release behavior, and thus had potential application values in drug controlled delivery. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4429–4439