Synthesis and characterization of temperature‐sensitive block copolymers from poly(N‐isopropylacrylamide) and 4‐methyl‐ε‐caprolactone or 4‐phenyl‐ε‐caprolactone

This study synthesizes thermally sensitive block copolymers poly(N‐isopropylacrylamide)‐b‐poly(4‐methyl‐ε‐caprolactone) (PNIPA‐b‐PMCL) and poly(N‐isopropylacrylamide)‐b‐poly(4‐phenyl‐ε‐caprolactone) (PNIPA‐b‐PBCL) by ring‐opening polymerization of 4‐methyl‐ε‐caprolactone (MCL) or 4‐phenyl‐ε‐caprolactone (BCL) initiated from hydroxy‐terminated poly(N‐isopropylacrylamide) (PNIPA) as the macroinitiator in the presence of SnOct₂ as the catalyst. This research prepares a PNIPA bearing a single terminal hydroxyl group by telomerization using 2‐hydroxyethanethiol (ME) as a chain‐transfer agent. These copolymers are characterized by differential scanning calorimetry (DSC), ¹H‐NMR, FTIR, and gel permeation chromatography (GPC). The thermal properties (T_g) of diblock copolymers depend on polymer compositions. Incorporating larger amount of MCL or BCL into the macromolecular backbone decreases T_g. Their solutions show transparent below a lower critical solution temperature (LCST) and opaque above the LCST. LCST values for the PNIPA‐b‐PMCL aqueous solution were observed to shift to lower temperature than that for PNIPA homopolymers. This work investigates their micellar characteristics in the aqueous phase by fluorescence spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The block copolymers formed micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range of 0.29–2.74 mg L^?1, depending on polymer compositions, which dramatically affect micelle shape. Drug entrapment efficiency and drug loading content of micelles depend on block polymer compositions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis and characterization of temperature‐responsive poly(vinyl alcohol)‐based copolymers

A poly(vinyl alcohol) (PVA)/sodium acrylate (AANa) copolymer was synthesized to improve the water solubility of PVA at the ambient temperature. Furthermore, a series of temperature‐responsive acetalyzed poly(vinyl alcohol) (APVA)‐co‐AANa samples of various chain lengths, degrees of acetalysis (DAs), and comonomer contents were prepared via an acid‐catalysis process. Fourier transform infrared and ¹H‐NMR techniques were used to analyze the compositions of the copolymers. The measurement of the turbidity change for APVA‐co‐AANa aqueous solutions at different temperatures revealed that the lower critical solution temperature (LCST) of the copolymers could be tailored through the control of the molecular weight of the starting PVA‐co‐AANa, DA, and comonomer ratios. Lower LCSTs were observed for APVA‐co‐AANa with a longer chain length, a higher DA, and fewer acrylic acid segments. In addition, the LCSTs of the APVA‐co‐AANa aqueous solutions appeared to be salt‐sensitive. The LCSTs decreased as the concentration of NaCl increased. Moreover, atomic force microscopy images of APVA‐co‐AANa around the LCST also proved the temperature sensitivity. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis of well‐defined comb‐like amphiphilic copolymers with protonizable units in the pendent chains: 2. Poly(2‐(dimethylamino)ethyl methacrylate) grafted poly(methyl methacrylate‐co‐2‐hydroxyethyl methacrylate) copolymers and their association behavior in aqueous solution

Narrow‐distribution, well‐defined comb‐like amphiphilic copolymers are reported in this work. The copolymers are composed of poly(methyl methacrylate‐co‐2‐hydroxyethyl methacrylate) (P(MMA‐co‐HEMA)) as the backbones and poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) as the grafted chains, with the copolymer backbones being synthesized via atom‐transfer radical polymerization (ATRP) and the grafted chains by oxyanionic polymerization. The copolymers were characterized by gel permeation chromatography (GPC), Fourier‐transform infrared (FT‐IR) spectroscopy and ¹H NMR spectroscopy. The aggregation behavior in aqueous solutions of the comb‐like amphiphilic copolymers was also investigated. ¹H NMR spectroscopic and surface tension measurements all indicated that the copolymers could form micelles in aqueous solutions and they possessed high surface activity. The results of dynamic light scattering (DLS) and scanning electron microscopy (SEM) investigations showed that the hydrodynamic diameters of the comb‐like amphiphilic copolymer aggregates increased with dilution. Because of the protonizable properties of the graft chains, the surface activity properties and micellar state can be easily modulated by variations in pH. Copyright © 2004 Society of Chemical Industry     

Preparation and aqueous solution behavior of a ph‐responsive branched copolymer based on 2‐(diethylamino)ethyl methacrylate

pH‐Responsive amphiphilic branched copolymers were prepared from poly(ethylene glycol) methyl ether methacrylate (PEGMA), 2‐(diethylamino)ethyl methacrylate (DEAEMA), 2‐(tert‐butylamino)ethyl methacrylate (tBAEMA), and ethylene glycol dimethacrylate (EGDMA) utilizing a thiol‐modified free radical polymerization. The molecular structures of copolymers were confirmed by proton nuclear magnetic resonance spectroscopy (¹H NMR) and triple‐detection gel permeation chromatography (tri‐GPC). The aqueous solution behaviors of the obtained copolymers were investigated by dynamic light scattering (DLS). The DLS data showed that about 16 nm polymer particles comprising of hydrophobic poly(tert‐butylamino)ethyl methacrylate (PtBAEMA) and poly(diethylaminoethyl methacrylate (PDEAEMA) core, hydrophilic PEGMA corona were formed above pH 8. With the decrease of pH from 8 to 6, a dramatic increase in the hydrodynamic radius of polymer particles from 16 nm to 130 nm was observed resulting from the protonation of the PDEAEMA segment. Moreover, in vitro drug release behaviors of the resulting polymer assemblies at different pH values were also investigated to evaluate their potential as sustained release drug carriers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42183.     

Thermoresponsive sodium alginate‐g‐poly(N‐isopropylacrylamide) copolymers III. Solution properties

Stimuli‐responsive biocompatible and biodegradable materials can be obtained by combining polysaccharides with polymers exhibiting lower critical solution temperature (LCST) phase behavior, such as poly(N‐isopropylacrylamide) (PNIPAAm). The behavior of aqueous solutions of sodium alginate (NaAl) grafted with PNIPAAm (NaAl‐g‐PNIPAAm) copolymers as a function of composition and temperature is presented. The products obtained exhibit a remarkable thermothickening behavior in aqueous solutions if the degree of grafting, the concentration, and the temperature are higher than some critical values. The sol–gel‐phase transition temperatures have been determined. It was found that at temperatures below LCST the systems behave like a solution, whereas at temperatures above LCST, the solutions behave like a stiff gel, because of PNIPAAm segregation. This behavior is reversible and could find applications in tissue engineering and drug delivery systems. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Effect of intermolecular and intramolecular forces on hydrodynamic diameters of poly(N‐isopropylacrylamide) copolymers in aqueous solutions

A novel copolymer, poly(N‐isopropylacrylamide‐co‐hydroxypropyl methacrylate‐co‐3‐trimethoxysilypropyl methacrylate) has been synthesized and the hydrodynamic diameters in various aqueous solutions under different temperatures are determined by dynamic light scattering. The results show that the hydrodynamic diameters of copolymers have no obvious change in each working solution below lower critical solution temperature (LCST); across LCST, the diameters increased suddenly at different initial temperature in various aqueous solutions; above LCST, they decreased slightly as the temperature increased in UHQ water, and increased continuously with increasing temperature or salt concentration in saline solutions, and reduced with the rising of pH value in pH buffer. These are attributed to different intermolecular and intramolecular forces leading to disparity in dimension, conformation, and LCST of copolymers. The hydrogen bonding between water molecules and copolymer chains could maintain size and conformation of copolymer single chain; the hydrogen bonding between amide linkages and hydrophobic interactions between isopropyl groups result in intramolecular collapse and intermolecular aggregation; the electrostatic repulsion weakens aggregation extent of copolymers. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Phase behavior of temperature‐ and pH‐sensitive poly(acrylic acid‐g‐N‐isopropylacrylamide) in dilute aqueous solution

Several different composition temperature‐ and pH‐sensitive poly(acrylic acid‐g‐N‐isopropylacrylamide) (P(AA‐g‐NIPAM)) graft copolymers were synthesized by free‐radical copolymerization utilizing macromonomer technique. The phase behavior and conformation change of P(AA‐g‐NIPAM) in aqueous solutions were investigated by UV–vis transmittance measurements, fluorescence probe, and fluorescence quenching techniques. The results demonstrate that the P(AA‐g‐NIPAM) copolymers have temperature‐ and pH‐sensitivities, and these different composition graft copolymers have different lower critical solution temperature (LCST) and critical phase transition pH values. The LCST of graft copolymer decreases with increasing PNIPAM content, and the critical phase transition pH value increases with increasing Poly(N‐isopropylacrylamide) (PNIPAM) content. At room temperature (20°C), different composition of P(AA‐g‐NIPAM) graft copolymers in dilute aqueous solutions (0.001 wt %) have a loose conformation, and there is no hydrophobic microdomain formation within researching pH range (pH 3 ～ 10). In addition, for the P(AA‐g‐NIPAM) aqueous solutions, transition from coil to globular is an incomplete reversible process in heating and cooling cycles. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

A study on solution properties of poly(N,N‐diethylacrylamide‐co‐acrylic acid)

Poly(N,N‐diethylacrylamide) (PDEA), poly(acrylic acid) (PAA), and a series of (N,N‐diethylacrylamide‐co‐acrylic acid) (DEA‐AA) random copolymers were synthesized by the method of radical polymerization. The measurement of turbidity showed that the phase behaviors of the brine solutions of the copolymers changed dramatically with the mole fraction of DEA (x) in these copolymers. Copolymers cop6 (x = 0.06) and cop11 (x = 0.11) in which acrylic acid content was higher presented the upper critical solution temperature (UCST) phase behaviors similar to PAA. Copolymer cop27 (x = 0.27) presented the lower critical solution temperature (LCST) behavior similar to PDEA. While copolymer cop18 (x = 0.18) in which acrylic acid content was moderate presented both UCST and LCST behaviors. The solution properties of the polymers were investigated by measurements of viscosity, fluorescence, and pH. It is reasonable to suggest that the sharp change of the phase behavior may be attributed to the interaction between acrylamide group and carboxylic group in the (DEA‐AA) copolymers. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Preparation and thermal response behavior of poly(N‐isopropylacrylamide‐co‐a crylic acid) microgels via soap‐free emulsion polymerization based on AIBN initiator

Poly(N‐isopropylacrylamide‐co‐acrylic acid) (poly(NIPAM‐co‐AA)) microgels with different copolymer compositions were prepared through soap‐free emulsion polymerization at 80°C, and 2, 2′‐azobisisobutyronitrile (AIBN) was used as initiator. Scanning electron microscope (SEM) characterization shows that the prepared microgels are regular and smooth and not easy to distort. Result of ¹H‐NMR characterization shows that with increasing of the initial concentration of AA (AA in feed), the AA content in polymer chains increases. The thermal response of microgels latex was investigated by UV‐3010 spectrophometer through detecting the transmittance of the latex at different temperature in the range of 190–900 nm. The thermal response of the poly(NIPAM‐co‐AA) microgels was tested by dynamic light scattering (DLS). The results show that with the increase of AA content in polymer chains, the low critical solution temperature (LCST) of microgels latex first decreases and then increases. Still, with increasing of AA in poly(NIPAM‐co‐AA) microgels, the LCST of microgels first increases and then decreases. The basic reasons causing the changes of LCST of microgels latex and microgels are interpreted clearly in this article from the perspective of hydrogen bonding interaction. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) graft copolymers and their application as carriers for drug delivery system

Poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) [P(NIPAM‐co‐HEMA)] copolymer was synthesized by controlled radical polymerization from respective N‐isopropylacrylamide (NIPAM) and hydroxyethyl methacrylate (HEMA) monomers with a predetermined ratio. To prepare the thermosensitive and biodegradable nanoparticles, new thermosensitive graft copolymer, poly(L ‐lactide)‐graft‐poly(N‐isoporylacrylamide‐co‐hydroxyethyl methacrylate) [PLLA‐g‐P(NIPAM‐co‐HEMA)], with the lower critical solution temperature (LCST) near the normal body temperature, was synthesized by ring opening polymerization of L ‐lactide in the presence of P(NIPAM‐co‐HEMA). The amphiphilic property of the graft copolymers was formed by the grafting of the PLLA hydrophobic chains onto the PNIPAM based hydrophilic backbone. Therefore, the graft copolymers can self‐assemble into uniformly spherical micelles ò about 150–240 nm in diameter as observed by the field emission scanning electron microscope and dynamic light scattering. Dexamethasone can be loaded into these nanostructures during dialysis with a relative high loading capacity and its in vitro release depends on temperature. Above the LCST, most of the drugs were released from the drug‐loaded micelles, whereas a large amount of drugs still remains in the micelles after 48 h below the LCST. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Synthesis of amphiphilic temperature‐sensitive poly(N‐isopropylacrylamide)‐block‐poly(tetramethylene carbonate) block copolymers and micellar characterization

Amphiphilic thermally sensitive poly(N‐isopropylacrylamide)‐block‐poly(tetramethylene carbonate) block copolymers were synthesized by ring‐opening polymerization of tetramethylene carbonate with hydroxyl‐terminated poly(N‐isopropylacrylamide) (PNiPAAm) as macro‐initiator in the presence of stannous octoate as catalyst. The synthesis involved PNiPAAm bearing a single terminal hydroxyl group prepared by telomerization using 2‐hydroxyethanethiol as a chain‐transfer agent. The copolymers were characterized using ¹H NMR and Fourier transform infrared spectroscopy and gel permeation chromatography. Their solutions show reversible changes in optical properties: transparent below the lower critical solution temperature (LCST) and opaque above the LCST. The LCST depends on the polymer composition and the media. Owing to their amphiphilic characteristics, the block copolymers form micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range 1.11–22.9 mg L^?1. Increasing the hydrophobic segment length or decreasing the hydrophilic segment length in the amphiphilic diblock copolymers produces lower CMCs. A core‐shell structure of the micelles is evident from ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopic analyses of micelle morphology show a spherical structure of both blank and drug‐loaded micelles. The blank and drug‐loaded micelles have an average size of less than 130 nm. Observations show high drug‐entrapment efficiency and drug‐loading content for the drug‐loaded micelles. Copyright © 2010 Society of Chemical Industry     

Thermoresponsive behaviour in aqueous solution of poly(maleic acid‐alt‐vinyl acetate) grafted with poly(N‐isopropylacrylamide)

The synthesis of a thermoresponsive graft copolymer consisting of a maleic acid/vinyl acetate alternating copolymer backbone (MAc‐alt‐VA) and poly(N‐isopropylacrylamide) (PNIPAM) side chains is reported. Turbidimetric measurements in dilute aqueous solutions showed that no macroscopic phase separation takes place when the temperature is raised above the lower critical solution temperature (LCST) of PNIPAM, even at pH = 2. Moreover, in semi‐dilute aqueous solutions, a pronounced thermally induced viscosity increase (thermothickening) was observed. This thermoresponsive behaviour has been attributed to the interconnection of the hydrophilic MAc‐alt‐VA graft copolymer backbones by means of the hydrophobic PNIPAM side chain aggregates formed as the temperature increases above the LCST of this polymer. Copyright © 2004 Society of Chemical Industry     

A novel approach for albumin determination in aqueous media by using temperature‐ and pH‐sensitive N‐isopropylacrylamide‐co‐N‐[3‐(dimethylamino)‐propyl]methacrylamide random copolymers

Random copolymers of N‐isopropylacrylamide (NIPA) and N‐[3‐(dimethylamino)propyl]methacrylamide (DMAPM) were synthesized by solution polymerization using azobisizobutyronitrile as the initiator in 1,4‐dioxane at 60°C. NIPA‐co‐DMAPM copolymer exhibited both temperature and pH sensitivity. Thermally reversible phase transitions were observed both in the acidic and the alkaline pH regions for copolymers produced with different DMAPM/NIPA feed ratios. The pH dependency of the lower critical solution temperature (LCST) was stronger for copolymers produced with higher DMAPM feed concentrations. NIPA‐co‐DMAPM random copolymer was also sensitive to the albumin concentration. In the presence of albumin, thermally irreversible phase transitions were observed in slightly acidic and neutral media. However, reversible transitions were obtained in aqueous media containing albumin at basic pH. The phase‐transition temperature of NIPA‐co‐DMAPM copolymer significantly decreased with increasing albumin concentration at both acidic and alkaline pH values. This behavior was explained by albumin binding onto the copolymer chains by means of H‐bond formation between the dimethylamino groups of the copolymer and the carboxyl groups of albumin. For a certain range of albumin concentration, the phase‐transition temperature exhibited a linear decrease with increasing albumin concentration. By utilizing this behavior, a simple albumin assay was developed. The results indicated that NIPA‐co‐DMAPM copolymer could be utilized as a new reagent for the determination of albumin concentration in the aqueous medium. The proposed method was valid for the albumin concentration range of 0–4000 μg/mL. The protein concentrations commonly utilized in biotechnological studies fall in the range of the proposed method. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2060–2071, 2002; DOI 10.1002/app.10503     

Stimuli‐responsive properties of aminophenylboronic acid‐carrying thermosensitive copolymers

Thermosensitive copolymers of N‐isopropylacrylamide (NIPA) and N‐acryloxysuccinimide (NASI) were obtained by solution polymerization using azobisisobutyronitrile as the initiator in a tetrahydrofuran–toluene mixture at 65 °C. A boronic acid‐carrying ligand, m‐aminophenylboronic acid (APBA) was covalently attached to the thermosensitive copolymer via the reaction between amino and succinimide groups. APBA‐coupled thermosensitive copolymer exhibited both temperature and pH sensitivity. Thermally reversible phase transitions were observed both in the acidic and alkaline pH region for the APBA‐modified copolymers obtained with different NASI feed concentrations. In our study, ribonucleic acid (RNA) was selected as a biomolecule having reactive groups which could potentially interact with the boronic acid functionality. The response of boronic acid‐carrying thermosensitive copolymer against RNA was investigated in aqueous media in the pH range 4–9. In the acidic pH region, an increase was observed in the lower critical solution temperature (LCST) of the APBA‐coupled thermosensitive copolymer with increasing RNA concentration. However, LCST decreased with increasing RNA concentration at both neutral and alkaline pH values. The LCST of the APBA‐attached copolymer varied linearly with the RNA concentration at pH of 3, 4 and 7. © 2003 Society of Chemical Industry     

Biodegradable polymersomes from four‐arm PEG‐b‐PDLLA for encapsulating hemoglobin

A series of four‐arm star block copolymers poly(ethylene glycol)‐block‐poly(d,l ‐lactide) (PEG‐PDLLA) with different hydrophobic length were synthesized by ring‐opening polymerization of lactide and characterized using ¹H NMR and gel permeation chromatography (GPC). These copolymers could self‐assemble in aqueous solution to form the vesicle structure with controlled size and morphologies. Transmission electron microscopy (TEM) and DLS show the polymersomes are spherical with diameter of 70～500 nm. The polymersomes made by direct hydration of copolymer thin films in water exhibit the controllable ability of encapsulating hemoglobin under mild condition. The hemoglobin content in the polymersomes could reach to 35 wt %. More importantly, the encapsulated hemoglobin keeps its own bioactivity and is capable of binding oxygen. This hemoglobin‐encapsulated four‐arm PEG‐PLA polymersomes could have the potential to be applied as an artificial oxygen carrier for transfusion. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40433.     

Synthesis and tunable thermoresponsive solution morphologies of 2,2‐bis‐methylolpropionic acid dendron–azobenzene–poly(N‐isopropyl acrylamide) copolymers

Amphiphilic temperature‐ and photoresponsive linear–dendritic block copolymers comprising second‐generation acetonide‐2,2‐bis‐methylolpropionic acid‐based polyester dendron and linear poly(N‐isopropyl acrylamide) (PNIPAM) linked by an azobenzene unit were synthesized using atom transfer radical polymerization (ATRP) followed by click chemistry. Linear PNIPAM precursor was prepared from an azide‐functionalized azobenzene containing ATRP initiator. Two polymers obtained by varying the chain length of the PNIPAM block showed different morphologies and lower critical solution temperature (LCST) values in aqueous solution. Complete change in morphology of the two polymers into large spherical aggregates and nanotubes, respectively, was observed upon heating the micellar solution above LCST. The azobenzene unit was found to undergo trans–cis photoisomerization in the assemblies and caused a change in the microenvironment of an encapsulated hydrophobic dye without any release. Acetonide groups on the dendron were deprotected to afford hydroxylated polymer that showed well‐defined morphologies above the LCST and after heating–cooling cycle while significant dye encapsulation was seen only above the LCST. © 2017 Society of Chemical Industry     

Water‐solution properties of a hydrophobically modified poly(N‐isopropylacrylamide)

To study the water‐solution properties of a hydrophobically modified poly(N‐isopropylacrylamide) (PNIPAM) which is temperature‐sensitive, the copolymer of N‐isopropylacrylamide (NIPAM) and octadecyl acrylate (ODA) was synthesized. The aggregation behavior of the copolymer was studied by surface tension and fluorescence probe methods. Simultaneously, the phenomenon of the lower critical solution temperature (LCST) of the copolymer in an aqueous solution with increase of the temperature was also studied using the fluorescence probe method. The results showed that phase separation occurred in an aqueous solution of the copolymer when the temperature was increased to its LCST. The π‐A isotherms for the copolymer molecules, as an insoluble monolayer on the water–air interface, was determined by the Langmuir–Blodgett (L–B) method. The abnormal phenomenon, by which the monolayer of the copolymer molecules became more and more condensed with increase of the temperature, was observed. It further indicated that phase separation of the copolymer occurred by another method. In addition, to prove the thermosensitive effect of the copolymer on the release behavior of liposomes, small unilamellar vesicles entrapped with 5(6)‐carboxyfluorescein [5(6)‐CF] were coated with the copolymer. We found that the coating of the copolymer resulted in the reduction of the release below 30°C and enhancement of the release above 30°C, indicating that there are obvious interactions between the copolymer and the liposomes. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 247–255, 2000     

pH‐ and temperature‐sensitive microfiltration membranes from blends of poly(vinylidene fluoride)‐graft‐poly(4‐vinylpyridine) and poly(N‐isopropylacrylamide)

The copolymer poly(vinylidene fluoride)‐graft‐poly(4‐vinylpyridine) (PVDF‐g‐P4VP) was prepared through the graft copolymerization of poly(vinylidene fluoride) with 4‐vinylpyridine. Through the blending of the PVDF‐g‐P4VP copolymer with poly(N‐isopropylacrylamide) (PNIPAm) in an N‐methyl‐2‐pyrrolidone solution, PVDF‐g‐P4VP/PNIPAm membranes were fabricated by phase inversion in aqueous media. Elemental analyses indicated that the blend concentration of PNIPAm in the blend membranes increased with an increase in the blend ratio used in the casting solution. Scanning electron microscopy revealed that the membrane surface tended to corrugate at a low PNIPAm concentration and transformed into a smooth morphology at a high PNIPAm concentration. The surface morphology and pore size distribution of the microfiltration membranes could be regulated by the blend concentration of the casting solution, temperature, pH, and ionic strength of the coagulation bath. X‐ray photoelectron spectroscopy revealed a significant enrichment of PNIPAm on the membrane surface. The flux of aqueous solutions through the blend membranes exhibited a pH‐ and temperature‐dependent behavior. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4089–4097, 2006     

Vesicular and micellar self‐assembly of stimuli‐responsive poly(N‐isopropyl acrylamide‐b‐9‐anthracene methyl methacrylate) amphiphilic diblock copolymers

Dually responsive amphiphilic diblock copolymers consisting of hydrophilic poly(N‐isopropyl acrylamide) [poly(NIPAAm)] and hydrophobic poly(9‐anthracene methyl methacrylate) were synthesized by reversible addition fragmentation chain‐transfer (RAFT) polymerization with 3‐(benzyl sulfanyl thiocarbonyl sulfanyl) propionic acid as a chain‐transfer agent. In the first step, the poly(NIPAAm) chain was grown to make a macro‐RAFT agent, and in the second step, the chain was extended by hydrophobic 9‐anthryl methyl methacrylate to yield amphiphilic poly(N‐isopropyl acrylamide‐b‐9‐anthracene methyl methacrylate) block copolymers. The formation of copolymers with three different hydrophobic block lengths and a fixed hydrophilic block was confirmed from their molecular weights. The self‐assembly of these copolymers was studied through the determination of the lower critical solution temperature and critical micelle concentration of the copolymers in aqueous solution. The self‐assembled block copolymers displayed vesicular morphology in the case of the small hydrophobic chain, but the morphology gradually turned into a micellar type when the hydrophobic chain length was increased. The variations in the length and chemical composition of the blocks allowed the tuning of the block copolymer responsiveness toward both the pH and temperature. The resulting self‐assembled structures underwent thermally induced and pH‐induced morphological transitions from vesicles to micelles and vice versa in aqueous solution. These dually responsive amphiphilic diblock copolymers have potential applications in the encapsulation of both hydrophobic and hydrophilic drug molecules, as evidenced from the dye encapsulation studies. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46474.     

Synthesis of thermoresponsive polymeric micelles of PNIPAAm‐b‐OMMA as a drug carrier for loading and controlled release of prednisolone

We synthesized a drug delivery system of poly(N‐isopropylacrylamide)‐b‐oligo(methyl methacrylate) (PNIPAAm‐b‐OMMA) via polycondensation of two homopolymers in 1,4‐dioxane. The products are characterized by FT‐IR and ¹H‐NMR spectra and TEM. The PNIPAAm‐b‐OMMA copolymer micelles in aqueous solution present the same lower critical solution temperature (LCST) as the unmodified PNIPAAm, owing to the formation of a core–shell micellar structure that the hydrophilic shell shields the hydrophobic inner OMMA core from interacting with water. The micelle carriers exhibit two heterogeneous microdomains: a hydrophobic inner core capable of highly solubilizing hydrophobic prednisolone molecules, plus a hydrated outer shell that stabilizes this micellar structure below its LCST. Moreover, the micelle carriers show reversible thermoresponsive aggregation/dispersion in response to temperature cycles through the LCST. By using the antiinflammation drug prednisolone as model drug, it is found that the PNIPAAm‐b‐OMMA drug carrier could prolong the release time and control the release amount by changing the temperature. Accordingly, this copolymer micelle may provide as an effective drug carrier for drug control and release. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009