Epoxidized poly(N‐isopropyl acrylamide)‐b‐epoHTPB‐b‐poly(N‐isopropyl acrylamide) triblock copolymer micelle nanoparticles for 10‐hydroxycamptothecin drug release

Thermoresponsive poly(N‐isopropyl acrylamide) (PNIPAM)‐block‐hydroxy‐terminated polybutadine‐block‐PNIPAM triblock copolymers were synthesized by atom transfer radical polymerization; this was followed by the in situ epoxidation reaction of peracetic acid. The copolymers were characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, and size exclusion chromatography measurements, and their physicochemical properties in aqueous solution were investigated by surface tension measurement, fluorescent spectrometry, ultraviolet–visible transmittance, transmission electron microscopy observations, dynamic light scattering, and so on. The experimental results indicate that the epoxidized copolymer micelle aggregates retained a spherical core–shell micelle structure similar to the control sample. However, they possessed a decreased critical aggregate concentration (CAC), increased hydrodynamic diameters, and a high aggregation number and cloud point because of the incorporation of epoxy groups and so on. In particular, the epoxidized copolymer micelles assumed an improved loading capacity and entrapment efficiency of the drug, a preferable drug‐release profiles without an initial burst release, and a low cytotoxicity. Therefore, they were more suitable for the loading and delivery of the hydrophobic drug as a controlled release drug carrier. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41877.     

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.     

Poly(ε‐caprolactone)‐graft‐poly(N‐isopropylacrylamide) amphiphilic copolymers prepared by a combination of ring‐opening polymerization and atom transfer radical polymerization: Synthesis,self‐assembly,and thermoresponsive property

Thermoresponsive graft copolymers of ε‐caprolactone and N‐isopropylacrylamide were synthesized by a combination of ring‐opening polymerization and the sequential atom transfer radical polymerization (ATRP). The copolymer composition, chemical structure, and the self‐assembled structure were characterized. The graft length and density of the copolymers were well controlled by varying the feed ratio of monomer to initiator and the fraction of chlorides along PCL backbone, which is acting as the macroinitiator for ATRP. In aqueous solution, PCL‐g‐PNIPAAm can assemble into the spherical micelles which comprise of the biodegradable hydrophobic PCL core and thermoresponsive hydrophilic PNIPAAm corona. The critical micelle concentrations of PCL‐g‐PNIPAAm were determined under the range of 6.4–23.4 mg/L, which increases with the PNIPAAm content increasing. The mean hydrodynamic diameters of PCL‐g‐PNIPAAm micelles depend strongly on the graft length and density of the PNIPAAm segment, allowing to tune the particle size within a wide range. Additionally, the PCL‐g‐PNIPAAm micelles exhibit thermosensitive properties and aggregate when the temperature is above the lower critical solution temperature. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41115.     

Self‐assembly of poly(3‐hexyl thiophene)‐b‐poly(ethylene oxide) into cylindrical micelles in binary solvent mixtures

Asymmetric block copolymer based on regioregular poly(3‐hexyl thiophene) (P3HT) and poly(ethylene oxide) (PEO) was synthesized through Heck reactions. The addition of PEO block has no influence in the effective conjugation length of P3HT block and apparently provides colloidal stability for the formation of stable nanostructures. Introduction of poor solvent to good solvent containing P3HT‐b‐PEO will induce the crystallization‐driven assembly of the P3HT into cylindrical micelles with a P3HT core, owing to π–π stacking of the conjugated backbone of P3HT. The absorption spectra of the cylindrical micelles reveal a red shift as compared to the polymer in good solvent, indicating the extension of conjugation length with an improved π–π stacking of the polymer chains within the cylindrical micelles. Our results indicated that cylindrical micelles with varied diameter and length can be obtained when solvent properties were varied using several different binary solvent mixtures. More interestingly, we demonstrate that ultrasonic processing can fragment the cylindrical micelles only when the ratio of poor solvent increases. This provides a facile and effective way to fabricate cylindrical micelles for applications in the area of polymer solar cell as well as organic optoelectronics device. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41186.     

Self‐assembly micelles from novel tri‐armed star C3‐(PS‐b‐PNIPAM) block copolymers for anticancer drug release

Novel tri‐armed star polystyrene‐block‐poly(N‐isopropylacrylamide) block copolymers with trimesic acid as central molecules were synthesized by successive two‐step atom transfer radical polymerization, and confirmed by Fourier‐transform infrared spectra, ¹H nuclear magnetic resonance, and laser light scattering gel chromatography system. The copolymers could self‐assemble into spherical core‐shell micelles in aqueous media independent on drug loading. Physicochemical properties of the blank and drug‐loaded micelles were examined by surface tension, fluorescence spectroscopy, UV‐vis, transmission electron microscope, and dynamic light scattering measurements. The copolymer micelles exhibited thermo‐triggered phase transition, with low critical solution temperature of 33.7 and 34.6°C, varying with copolymer compositions. The critical aggregate concentrations were 11.62 and 47.61 mg L^?1, and hydrodynamic diameters from 200 to 220 nm. Water‐insoluble 10‐hydroxycamptothecine was encapsulated into the micelle aggregates to investigate the change in the resulting physicochemical parameters, thermo‐triggered in vitro drug release, and the applicability as drug targeting release carriers. MTT assays were carried out to uncover cytotoxicity of the newly developed micelle‐based drug formulations. © 2014 American Institute of Chemical Engineers AIChE J, 61: 35–45, 2015     

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     

Synthesis and self‐assembly of amphiphilic star‐block copolymers consisting of polyethylene and poly(ethylene glycol) segments

We report on the synthesis and self‐assembly in water of well‐defined amphiphilic star‐block copolymers with a linear crystalline polyethylene (PE) segment and two or three poly(ethylene glycol) (PEG) segments as the building blocks. Initially, alkynyl‐terminated PE (PE‐?) is synthesized via esterification of pentynoic acid with hydroxyl‐terminated PE, which is prepared using chain shuttling ethylene polymerization with 2,6‐bis[1‐(2,6‐dimethylphenyl) imino ethyl] pyridine iron (II) dichloride/methylaluminoxane/diethyl zinc and subsequent in situ oxidation with oxygen. Then diazido‐ and triazido‐terminated PE (PE‐(N₃)₂ and PE‐(N₃)₃) are obtained by the click reactions between PE‐? and coupling agents containing triazido or tetraazido, respectively. Finally, the three‐arm and four‐arm star‐block copolymers, PE‐b‐(PEG)₂ and PE‐b‐(PEG)₃, are prepared by click reactions between PE‐(N₃)₂ or PE‐(N₃)₃ and alkynyl‐terminated PEG. The self‐assembly of the resultant amphiphilic star‐block copolymers in water was investigated by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. It is found that, in water, a solvent selectively good for PEG blocks; these star‐block copolymer chains could self‐assemble to form platelet‐like micelles with insoluble PE blocks as crystalline core and soluble PEG blocks as shell. The confined crystallization of PE blocks in self‐assembled structure formed in aqueous solution is investigated by differential scanning calorimetry. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Thermoresponsive self‐assembled nanovesicles based on amphiphilic triblock copolymers and their potential applications as smart drug release carriers

A series of thermoresponsive triblock copolymers, methoxy poly(ethylene oxide)‐b‐poly(ε‐caprolactone)‐b‐poly(N‐isopropylacrylamide) (mPEO‐b‐PCL‐b‐PNIPAM), with different PCL and PNIPAM block lengths, were synthesized by a combination of ring opening polymerization and reversible addition‐fragmentation chain transfer polymerization techniques. The triblock copolymers undergo self‐assembly in aqueous solutions forming stable nanovesicles of various sizes with a lipid membrane structure similar to body cells as revealed by transmission electron microscopy. The nanovesicle is thermoresponsive, that is, its size is tunable using the temperature as a switch: shrinks at a temperature above the lower critical solution temperature (LCST) and expands at a temperature below the LCST. The corresponding LCST of the triblock copolymers is adjustable by varying the PNIAM segment length as well as the PCL segment length and covers a range from 33.9 to 41.0°C in water. The diameter of nanovesicles for mPEO_3k‐b‐PCL_5k‐b‐PNIPAM_13.2k is about 177.7 nm below the LCST and 138.9 nm above the LCST, as determined by dynamic light scattering. It was demonstrated using indomethacin, a popular anti‐inflammation medicine, that the triblock copolymers can effectively act as a drug release carrier under the right human physiological conditions, that is, store the drug at a lower temperature and release it at a higher temperature, possibly targeting at the lesion sites of human body. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41361.     

Fabrication of thermoresponsive,core‐crosslinked micelles based on poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} for the codelivery of doxorubicin and nucleic acid

Thermoresponsive amphiphilic copolymer, poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} with a branched structure was designed and synthesized by consecutive reversible addition–fragmentation chain‐transfer polymerization. The further hydrolysis of trimethoxysilyl functions in 3‐(trimethoxysilyl) propyl methacrylate units led to the fabrication of core‐crosslinked (CCL) micelles with silica crosslinks at temperatures above the lower critical solution temperature of the poly(N‐isopropyl acrylamide) block. The thermally induced structural and morphological changes of the CCL micelles in aqueous solution were investigated by transmission electron microscopy and ¹H‐NMR analyses. The resulting CCL micelles were further explored as nanocarriers for the codelivery of an anticancer drug and nucleic acid for enhanced therapeutic efficacy. The CCL micelles effectively condensed the nucleic acid and mediated higher gene transfer in the presence of serum than in serum‐free transduction. A cytotoxicity study revealed that whereas the pure CCL micelles exhibited unapparent cytotoxicity, the codelivery of p53 and doxorubicin with the CCL micelle formulation resulted in better treatment efficiency than sole chemotherapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41752.     

Thermosensitive polymeric micelles based on the triblock copolymer poly(d,l‐lactide)‐b‐poly(N‐isopropyl acrylamide)‐b‐poly(d,l‐lactide) for controllable drug delivery

A thermosensitive amphiphilic triblock copolymer, poly(d,l ‐lactide) (PLA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAAM)‐b‐PLA, was synthesized by the ring‐opening polymerization of d,l ‐lactide; the reaction was initiated from a dihydroxy‐terminated poly(N‐isopropyl acrylamide) homopolymer (HO‐PNIPAAM‐OH) created by radical polymerization. The molecular structure, thermosensitive characteristics, and micellization behavior of the obtained triblock copolymer were characterized with Fourier transform infrared spectroscopy, ¹H‐NMR, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. The obtained results indicate that the composition of PLA‐b‐PNIPAAM‐b‐PLA was in good agreement with what was preconceived. This copolymer could self‐assemble into spherical core–shell micelles (ca. 75–80 nm) in aqueous solution and exhibited a phase‐transition temperature around 26 °C. Furthermore, the drug‐delivery properties of the PLA‐b‐PNIPAAM‐b‐PLA micelles were investigated. The drug‐release test indicated that the synthesized PLA‐b‐PNIPAAM‐b‐PLA micelles could be used as nanocarriers of the anticancer drug adriamycin (ADR) to effectively control the release of the drug. The drug‐delivery properties of PLA‐b‐PNIPAAM‐b‐PLA showed obvious thermosensitive characteristics, and the release time of ADR could be extended to 50 h. This represents a significant improvement from previous PNIPAAM‐based drug‐delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45304.     

Amphiphilic star‐shaped poly(ε‐caprolactone)‐block‐poly(l‐lysine) copolymers with porphyrin core: Synthesis,self‐assembly,and cell viability assay

Star‐shaped copolymers poly(ε‐caprolactone)‐bolck‐poly(ε‐benzyloxycarbonyl‐l ‐lysine) (SPPCL‐b‐PZLLs) with porphyrin core were synthesized by a sequential ring‐opening polymerization (ROP) of CL and Nε‐Benzyloxycarbonyl‐l ‐lysine N‐Carboxyanhydride. After the deprotection of benzyloxycarbonyl groups in polylysine blocks, the star‐shaped amphiphilic copolymers SPPCL‐b‐PLLs were obtained. These amphiphilic copolymers can self‐assemble into micelles or aggregates in aqueous solution. Investigation shows that the morphology of micelles/aggregates varied according to the change of pH values of media, indicating the pH‐responsive property of SPPCL‐b‐PLL copolymers. Furthermore, associated with conjugated porphyrin cores, the SPPCL‐b‐PLL copolymers micelles showed a certain degree of Photodynamic Therapy (PDT) effects on tumor cells, suggesting its potential application as carrier for hydrophobic drug with additional therapeutic ability of inherent porphyrin segments. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40097.     

Synthesis and self‐assembling behaviors of biotinylated pluronic/poly(lactic acid) biocompatible block copolymers in aqueous solutions

Four kinds of Biotinylated Pluronic/PLA block copolymers were synthesized by two‐step reactions. Pluronic were firstly modified by biotin to obtain B‐Pluronic‐OH. Biotin‐Pluronic‐PLA block copolymers were then produced by ring‐opening polymerization of the monomer L ‐lactide using Biotin‐Pluronic‐OH as the initiator and stannous octoate (Sn(Oct)₂) as the catalyst. The self‐assembling behaviors of Biotin‐Pluronic‐PLA block copolymers in aqueous solutions were examined by fluorescence measurement, dynamic light scattering (DLS), and transmission electron microscopic (TEM) techniques. The size of Biotin‐F127‐PLA‐61, Biotin‐F87‐PLA, and Biotin‐P85‐PLA nanoparticles were determined to be 198, 229, and 257 nm, respectively, and their morphologies were found to be spherical micelles. Biotin‐F127‐PLA‐87 produces both spherical micelles and large compound micelles with the size of 127 and 906 nm. The cytotoxicity studies using human ovarian cancer cells OVCAR‐3 indicate that Biotin‐Pluronic‐PLA block copolymers have good biocompatibility. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Improved swelling–deswelling behavior of poly(N‐isopropyl acrylamide) gels with poly(N,N′‐dimethyl aminoethyl methacrylate) grafts

Thermoresponsive and pH‐responsive gels were synthesized from N‐isopropyl acrylamide (NIPA) and N,N′‐dimethyl aminoethyl methacrylate (DMAEMA) monomers. Gelation reactions were carried out with both conventional free‐radical polymerization (CFRP) and controlled free‐radical polymerization [reversible addition fragmentation transfer (RAFT)] techniques. The CFRP gels were prepared by polymerizing mixtures of NIPA and DMAEMA in 1,4‐dioxane in presence of N,N'‐methylene bisacrylamide (BIS) as cross‐linker. The RAFT gels were prepared by a the polymerization of NIPA via a similar process in the presence of different amounts of poly(N,N′‐dimethyl aminoethyl methacrylate) macro chain‐transfer agent and the crosslinker. These gels were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry. SEM analysis revealed a macroporous network structure for the RAFT gels, whereas their volume phase‐transition temperatures (VPTTs) were found to be in the range 32–34°C, close to that of poly(N‐isopropyl acrylamide) gels. However, the CFRP copolymer gels exhibited a higher VPTT; this increased with increasing DMAEMA content. The RAFT gels exhibited higher swelling capabilities than the corresponding CFRP gels and also showed faster shrinking–reswelling behavior in response to changes in temperature. All of the gels showed interesting pH‐responsive behavior as well. The unique structural attributes exhibited by the RAFT gels can potentially open up opportunities for developing new materials for various applications, for example, as adsorbents or carrier of drugs or biomolecules. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42749.     

Self‐assembly and drug delivery behaviors of thermo‐sensitive poly(t‐butyl acrylate)‐b‐poly(N‐isopropylacrylamide) micelles

Self‐assembly of thermo‐sensitive poly (t‐butyl acrylate)‐b‐poly(N‐isopropylacrylamide) (PtBA‐ b‐PNIPAM) micelles in aqueous medium and its applications in controlled release of hydrophobic drugs were described. PtBA‐b‐PNIPAM was synthesized by atom transfer radical polymerization and aggregated into thermo‐sensitive core‐shell micelles with regular spheres in water, which was confirmed by ¹H‐NMR, fluorescence spectroscopy, transmission electron microscopic (TEM), and UV–vis spectroscopic techniques. The critical micelle concentration of micelles decreased with the increase of the hydrophobic components. The anti‐inflammation drug naproxen (NAP) was loaded as the model drug into polymeric micelles, which showed a dramatic thermo‐sensitive fast/slow switching behavior around the lower critical solution temperature (LCST). When the temperature was enhanced above LCST, release of NAP from core‐shell micelles was accelerated ascribed to the temperature‐induced deformation of micelles. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Creating a smart textile via the self‐assembly of responsive polymer particles on poly(ethylene terephthalate) fibers

A novel method is presented for the construction of a hierarchical microstructure/nanostructure via the chemical self‐assembly of poly(N‐isopropyl acrylamide‐co‐acrylic acid) particles on polyester fibers. The textile of the particle‐bound fibers possessed smart wettability and an oil‐absorbing capacity. The wettability was dependent on the initial contact angle and spreading time of water droplets on the particle‐bound textile, which could be controlled with the content of acrylic acid inserted into the polymer chains. The wettability of the particle‐bound textile was responsive to the pH value. In addition, the textile was superoleophilic on an air–solid surface and could absorb oil quickly from water. The oil‐absorbing capacity could be controlled by the alteration of the pH value. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46834.     

Preparation of quadruple responsive polymeric micelles combining temperature‐, pH‐, redox‐, and UV‐responsive behaviors and its application in controlled release system

A novel series of quadruple responsive copolymers, poly(ethylene glycol)‐ss‐[poly(dimethylaminoethyl methacrylate)‐co‐poly(2‐nitrobenzyl methacrylate)] [PEG‐ss‐(PDMAEMA‐co‐PNBM)], were synthesized via atom transfer radical polymerization mediated by home‐made PEG‐based macro‐initiator labeled with disulfides. The obtained copolymers could self‐assemble in aqueous solution forming micelles with the disulfide bridge linking the hydrophilic coronas (PEG) and the hydrophobic cores (PDMAEMA‐co‐PNBM). Investigation on the resulted micelles indicated that the micelles could respond to various stimuli, that is, temperature, pH, the presence of dithiothreitol (DTT), and UV irradiation. Moreover, the responsive behavior of the micelles depends on the type of stimuli, that is, temperature change causes size change of the micelles, while UV irradiation leads to dissolution of the self‐assembled structures. Such stimulus‐dependent responsive behavior could be applied in smart materials that deal with multi‐tasks or in the construction of complex logic gate. The potential application of the multi‐responsive micelles in cargo release system was also evaluated using Nile Red (NR) as model molecule. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46675.     

Thermoresponsive poly(γ‐propyl‐l‐glutamate)‐graft‐(oligo ethylene glycol)s: Synthesis,characterization, and properties

A series of thermoresponsive poly(γ‐propyl‐_L‐glutamate)‐graft‐(oligo ethylene glycol)s (PPLG‐g‐OEGs) with different main‐chain and side‐chain lengths have been synthesized via copper‐mediated alkyne‐azide 1,3‐dipolar cycloaddition between poly(γ‐azidopropyl‐_L‐glutamate)s (PAPLG) and propargyl terminated oligo ethylene glycols (Pr‐OEGs). Fourier transform infrared spectrometer analysis revealed that PAPLG₁₀ adopted 39.4% β‐sheet, 47.4% α‐helix, and 13.2% random coil while PAPLG with longer main‐chain length (DP = 37 and 88) and PPLG‐g‐OEGs adopted exclusive α‐helix in the solid state. Circular dichroism analysis revealed that PPLG‐g‐OEGs adopted α‐helical conformations with helicities in the range of 50～100%. The thermoresponsive behaviors of PPLG‐g‐OEGs in water have been studied by dynamic light scattering. The polymer concentration, main‐/side‐chain length, and helicity collectively affected their cloud point temperatures. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41022.     

Synthesis,properties and self‐assembly of intelligent core‐shell nanoparticles based on chitosan with different molecular weight and N‐isopropylacrylamide

In this study, a series of chitosan‐graft‐poly(N‐isopropylacrylamide) (CTS‐g‐PNIPAAm) copolymers based on different molecular weight (Mw) of CTS and NIPAAm were synthesized through the polymerization of NIPAAm in an acid aqueous solution. The structures were verified by Fourier transform infrared and nuclear magnetic resonance. The influence of the CTS Mw on the properties of the resulting copolymers and self‐assembled nanoparticles was fully examined. The grafting ratio and grafting efficiency of the copolymers increased with the CTS Mw. All the copolymers have a similar low critical solution temperature of 33.5°C, which was independent of the CTS Mw. Furthermore, the copolymers were less temperature sensitive, when CTS Mw increased to 200 kDa. Besides, once the CTS Mw increased to 700 kDa, the copolymers were less pH sensitive near the tumor site (from pH 7.4 to 6.8). The copolymers could form uniform nanoparticles once the temperature increased to 34°C, which was reversible. After crosslinking by N,N‐methylenebisacrylamide (MBA), structurally stable nanoparticles could be obtained. The results from Transmission electron microscope (TEM) and Atomic force microscopy (AFM) showed that the MBA crosslinked nanoparticles were uniformly spherical with a loose structure. Surface tension method indicated that the critical aggregate concentrations were 0.045, 0.042, 0.037, and 0.036 mg mL^?1 prepared from CTS 50, 100, 200, and 700 kDa, respectively. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

6‐O‐dodecyl‐chitosan carbamate–based pH‐responsive polymeric micelles for gene delivery

pH‐responsiveness is highly desirable in the stimuli‐responsive controlled release because of the distinct advantages of the fast response of pH‐triggered release and the available pH‐difference between intra‐ and extra‐cells. The present work reported a kind of novel pH‐responsive polymeric micelles, which was derived from biopolymer of 6‐O‐dodecyl‐chitosan carbamate (DCC) and evaluated as gene‐controlled release vector. The amphiphilic and amino‐rich DDC was synthesized through a protection‐graft‐deprotection method. ¹³C CP/MAS NMR, FTIR, and elemental analysis identified that dodecyls were chemoselectively grafting at 6‐hydroxyls of chitosan via the pH‐responsive bonds of carbamate, and the substitute degree (SD) was 14%. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) showed that DCC self‐assembled into polymeric micelles in aqueous solutions. The DCC polymeric micelles formed complexes with pDNA, which was elucidated by Gel retardation, TEM, and DLS. Transfection and cytotoxicity assays in A549 cells showed that DCC polymeric micelles were suitable for gene delivery. The improved transfection was attributed to the pH‐responsiveness and the moderate pDNA‐binding affinity, which led to easier release of pDNA intra‐cells. The synthesized DCC polymeric micelles might be a promising and safe candidate as nonviral vectors for gene delivery. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42469.     

Thermosensitive copolymer synthesized by controlled living radical polymerization: Phase behavior of diblock copolymers of poly(N‐isopropyl acrylamide) families

In this study, we prepared a series of thermosensitive polymers with low polydispersity index (PDI) values by nitroxide‐mediated controlled radical polymerization (NMRP) with 2,2,6,6‐tetramethyl‐1‐piperdinyloxy nitroxide (TEMPO) as a stable nitroxide‐free radical. Poly(N‐isopropyl acrylamide) (PNIPAAm)‐block‐poly(N‐tert‐butyl acrylamide) (PNTBA) was successfully synthesized, first, through polymerization with N‐isopropyl acrylamide to obtain the reactive polymer PNIPAAm‐TEMPO and, second, through polymerization by the addition of N‐tert‐butyl acrylamide (NTBA). The added molar fraction of NTBA during the second polymerization was adjusted accordingly to obtain the final polymerization product, a thermosensitive polymer (PNIPAAm‐block‐PNTBA), which had a targeted lower critical solution temperature (LCST). The result shows that the synthesis method used in this study effectively controlled the formation of the polymer to obtain a low PDI. The thermosensitive block copolymer, PNIPAAm‐b‐PNTBA (molar ratio = 9:1), with LCSTs in the range 27.7–39.8°C, was obtained through controlled living radical polymerization with PNIPAAm–TEMPO. Specifically, the 5 wt % aqueous solution of PNIPAAm‐b‐PNTBA (molar ratio = 9:1) had an LCST of 37.4°C; this was close to body temperature, 37°C. The 5 wt % aqueous solution of PNIPAAm‐b‐PNTBA (molar ratio = 9:1) showed potential for use in biomedical applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43224.