Thermal characterization of biodegradable methoxy poly(ethylene glycol)-b-poly(d,l-lactide)/methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) blend nanoparticles

Biodegradable methoxy poly(ethylene glycol)-b-poly(d,l-lactide) (MPEG-b-PDLL) and methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-b-PCL) diblock copolymers were synthesized by ring-opening polymerization of DLL and CL monomers in bulk using stannous octoate, and MPEG as the initiating system. Surfactant-free MPEG-b-PDLL/MPEG-b-PCL blend nanoparticles were prepared by the nanoprecipitation method. The influences of block length and blend ratio on morphology, average size, and thermal properties of the blend nanoparticles were determined. The blend nanoparticles were spherical in shape. The average particle sizes slightly decreased as the MPEG-b-PCL blend ratio increased. ¹H-NMR and thermogravimetry revealed the different MPEG-b-PDLL/MPEG-b-PCL blend ratios of the nanoparticles. Differential scanning calorimetry showed that the MPEG-b-PCL crystallinity steadily decreased as the MPEG-b-PDLL blend ratio increased, suggesting miscible blending between the MPEG-b-PDLL and MPEG-b-PCL in the amorphous phase of the nanoparticle matrix.     

Synthesis of thermoresponsive polystyrene-based comb-type grafted poly(N-isopropylacrylamide)

Narrowly distributed polystyrene-g-p(N-isopropylacrylamide) (PSt-g-PNIPAM) was prepared by atom transfer radical polymerization (ATRP) of N-isopropylacrylamide using the brominated polystyrene as macroinitiator and CuCl combined with hexamethyltriethylenetetramine as catalyst. Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy confirmed the structure of PSt-g-PNIPAM. The gel permeation chromatography (GPC) showed that the graft copoly- mer had a single distribution peak with molecular weight, Mn (g/mol) of 19815 g/mol (using polystyrene as the standard). Differential scanning calorimetry (DSC) revealed that due to both effects of hydro- phobic isopropyl groups and hydrogen bonds in the amide group, the glass transition temperature (Tg) of PSt-g-PNIPAM enhanced 16.0 ℃ compared to the Tg of the polystyrene.     

Novel temperature-sensitive, β-cyclodextrin-incorporated poly(N-isopropylacrylamide) hydrogels for slow release of drug

Novel temperature-sensitive poly(N-isopropylacrylamide) hydrogels containing water-soluble -cyclodextrin polymer were prepared by forming semi-interpenetrating polymeric networks. Compared to the conventional poly(N-isopropylacrylamide) gel, the -cyclodextrin-incorporated hydrogels showed the same lower critical solution temperature due to the independence of the -cyclodextrin polymer in the networks. The release time of ibuprofen from the novel gel was significantly prolonged, which was presumably attributed to the formation of the inclusion complexes between the cyclodextrin groups and the drug molecules.Jian-Tao Zhang and Shi-Wen Huang have contributed equally to this work.     

pH-responsive star-shaped functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) with amino groups

Functional star-shaped 4-arm poly(ethylene glycol)-b-poly[(ε-caprolactone-co-γ-amino-ε-caprolactone)] (4-arm PEG-b-P(CL-co-ACL) was synthesized through ring-opening polymerization. The structure of the copolymer was confirmed by ¹H NMR, Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography (GPC). To further understand the copolymers, the difference of the conversion rate between ε-caprolactone (CL) and γ-(carbamic acid benzyl ester)-ε-caprolactone (CABCL) and the detailed deprotection condition were studied. The thermal property of the copolymer was analyzed by WAXR and differential scanning calorimetry (DSC), which demonstrated that the thermal property could be well adjusted. The pH-responsive behavior of the copolymers was studied in detail by dynamic light scattering (DLS), pH titration, and pyrene fluorescence methods, which indicated that it could form micelles and exhibit pH responsibility. Moreover, the copolymer was nontoxic and had good biocompatibility according to the results by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay.     

Effect of poly(4‑tert-butylstyrene) block length on the microphase structure of poly(ethylene oxide)-b-poly(4-vinylbenzyl chloride)-b-poly(4‑tert-butylstyrene) triblock terpolymers

A series of linear poly(ethylene oxide)-b-poly(4-vinylbenzyl chloride)-b-poly(4‑tert-butylstyrene) (PEO₁₁₃-b-PVBC₁₃₀-b-PtBS_x or E₁₁₃V₁₃₀T_x) triblock terpolymers with various lengths x (=20, 33, 66, 104, 215) of PtBS block were synthesized via a two-step reversible addition-fragmentation chain transfer (RAFT) polymerization. The E₁₁₃V₁₃₀T_x triblock terpolymers were non-crystalline because the PVBC and PtBS blocks strongly hindered the crystallization of PEO block. The effects of PtBS block length x on the phase structures of E₁₁₃V₁₃₀T_x triblock terpolymers were investigated by combined techniques of small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). It was found that with increasing x from 20 to 215, the phase structure of E₁₁₃V₁₃₀T_x triblock terpolymers became more ordered and changed from disordered structure, hexagonally-packed cylinder (HEX), hexagonally perforated layer (HPL), to lamellar (LAM) phase structures. Temperature-variable SAXS measurements showed that the HEX, HPL and LAM phase structures obtained for E₁₁₃V₁₃₀T₆₆, E₁₁₃V₁₃₀T₁₀₄ and E₁₁₃V₁₃₀T₂₁₅ by thermal annealing, respectively, were thermodynamically stable in the temperature range of 30–170 °C.     

Recent progress of poly (N-isopropylacrylamide) hybrid hydrogels: synthesis,fundamentals and applications – review

Hydrogels, having nanomaterials (e.g. nanoparticles and nanorods) incorporated inside their polymeric meshes, are generally called hybrid gels/hydrogels. These assemblies combine the properties of both hydrogels and nanomaterials in one system. These responsive hybrid hydrogels, particularly polymerized N-isopropylacrylamide (PoNip) polymeric gels, have been extensively exploited for various multi-disciplinary applications in the literature over the past two decades because of their unique and exquisite particulars. Next generation assemblies have been prepared by using the smart nature of these gels toward the general incentives (e.g. temperature, ionic strength, and pH) in the fields of nanocatalysis, water purification, drug delivery, photonics, and optics. This review presents an overview of the PoNip hybrid assemblies engineered over the past 7 years i.e. 2010–2016 and extensively discusses the interaction of the incorporated nanomaterial with the polymeric chains of the hydrogels as it is the most significant factor which makes these assemblies attractive for all the associated applications. Moreover, this article also describes the preparative routes, properties, classification, and applications of these hybrid hydrogels in the fields of medicine, environment, catalysis, and nanotechnology.     

Synthesis and micellar characterization of thermosensitive amphiphilic poly(ε-caprolactone)-b-poly(N-vinylcaprolactam) block copolymers

Poly(ε-caprolactone)-b-poly(N-vinylcaprolactam) (PCL-b-PVCL) block copolymers were synthesized as new biocompatible, thermosensitive, amphiphilic block polymers by a combination of ring-opening polymerization and reversible addition–fragmentation chain transfer (RAFT) polymerization, and their thermosensitive micellar behavior was examined. The PCL macro-chain-transfer agent was first synthesized by converting the end group of PCL-OH to O-ethyl xanthate, which was subsequently used for the RAFT polymerization of N-vinylcaprolactam. The critical micelle concentration of PCL-b-PVCL (M _n,NMR?=?56,300?g/mol, polydispersity index?=?1.18) was 0.026?mg/mL. The mean diameter of the PCL-b-PVCL micelles determined by transmission electron microscopy was 55?±?25?nm. The PCL-b-PVCL micelles exhibited repetitive aggregation and dispersion during reversible cooling and heating cycles between 20 and 40?°C due to the thermosensitive behavior of the PVCL shell. Overall, the PCL-b-PVCL block copolymers have potential applications in thermosensitive drug delivery applications.     

Confined lamella formation in crystalline-crystalline poly(ethylene oxide)-b-poly(ɛ-caprolactone) diblock copolymers

The real time and in situ investigation of the crystallization process and structure transitions of asymmetric crystalline-crystalline diblock copolymers from the melt was performed with synchrotron simultaneous SAXS/WAXS. The asymmetric poly(ethylene oxide)-b-poly(ε-caprolactone) diblock copolymers were chosen for the present study. It was shown that the short blocks crystallized later than the long blocks and final lamellar structure was formed in all of the asymmetric diblock copolymers. The final lamellar structure was confirmed by AFM observation. The SAXS data were analyzed with different methods for the early stage of the crystallization. The Guinier plots indicated that there were no isolated domains formed before the formation of lamellae in the asymmetric diblock copolymers during the crystallization process. Debye-Bueche plots implied the formation of correlated domains during crystallization.     

Effect of molecular architecture on micellization, drug loading and releasing of multi-armed poly(ethylene glycol)-b-poly(ε-caprolactone) star polymers

This study investigated the effect of molecular architecture of amphiphilic star polymers on micelle formation and drug loading and releasing. For this, multi-armed star block copolymers having poly(ethylene glycol) as a hydrophilic block and poly(ε-caprolactone) as a hydrophobic block were synthesized by using a divergent synthetic method consisting of a coupling reaction and a ring opening polymerization. The molecular weight and molecular weight distribution of the block copolymers were characterized by ¹H NMR and GPC measurements. Dynamic light scattering and fluorescence spectroscopic analysis were employed to observe micellization, drug loading, and drug release behaviors. We have figured out that the number of arms is a critical factor that changes critical micelle concentration as well as drug loading and releasing behaviors; increase in the number of arms not only led to lowering the critical micelle concentration and drug release rate but also increased the micelle size and drug loading efficiency.     

“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.     

Synthesis and Characterization of Triblock Terpolymers with three Potentially Crystallisable Blocks: Polyethylene-b-poly(ethylene oxide)-b-poly(ε-caprolactone)

A first attempt was made to produce novel ABC triblock terpolymers with three potentially crystallisable blocks: polyethylene (PE), poly(ethylene oxide) (PEO), and poly(ε-caprolactone) (PCL). Polybutadiene-b-poly(ethylene oxide) diblock copolymers were synthesized by living anionic polymerization. Then, a non-catalyzed thermal polymerization of ε-caprolactone from the hydroxyl end group of the PB-b-PEO diblock precursors was performed. Finally, hydrogenation by Wilkinson catalyst produced PE-b-PEO-b-PCL triblock terpolymers. Side reactions were detected that lead to the formation of undesired PCL-b-PEO diblock copolymers, however, these impurities were successfully removed by purification. A range of triblock terpolymers with PCL and PEO minor components were prepared. Topological restrictions on the PEO middle block prevented this block from crystallizing while the complex crystallization behavior of the PE and PCL blocks was documented by DSC and WAXS measurements.     

Electron transfer quenching of tris(2,2′-bipyridine) ruthenium (II) complex derivatives covalently linked to poly (N-isopropylacrylamide) in aqueous solutions

Tris(2,2-bipyridine) ruthenium(II) complex, ionic probe, was incorporated into poly (N-isopropylacrylamide) (PNIPA), which is known to be a thermoresponsive polymer, by a copolymerization method. Electron transfer quenching of the complex probe by methyl viologen was investigated as a function of temperature. The electron transfer quenching rate constant (k _q) in a globular state (higher temperature than the LCST (31°C)) is 4–5 times as large as that in a coil state (lower temperature) from the Stern-Volmer analysis. The result is quite different from the quenching of pyrene probe incorporated into PNIPA in the previous study. This is because hydrophilic ruthenium probe is located at the interface of polymer globular matrix even in a globular state, whereas pyrene probe was embedded into the hydrophobic matrix. The quenching behavior is discussed by a difference in molecular environment of the probes in phase transition of PNIPA in the aqueous solution.     

Change in Young’s modulus of poly(N-isopropylacrylamide) gels by volume phase transition

Mechanical properties of poly(N-isopropylacrylamide) (PNIPA) gels were examined both in swollen and collapsed state. Stress–strain curve of the gel in the swollen state was linear and the collapsed gel also showed almost linear stress–strain behavior. The initial Young’s modulus (E₀) in the collapsed state was much higher than that in the swollen state. The number of cross-links increased largely by the introduction of the physical cross-links due to collapse of the gels.     

Swelling–shrinking behaviors of poly(N-isopropylacrylamide) and poly(N-n-propylacrylamide) gels prepared by chemical and radiation crosslinking methods

The swelling and shrinking kinetics of thermosensitive gels based on N-isopropylacrylamide (NiPAAm) and N-n-propylacrylamide (NnPAAm) were studied. Four gels cylindrical in shape were prepared by two different methods: γ-ray irradiation to aqueous solutions of poly(NiPAAm) (PNiPAAm) or poly(NnPAAm) (PNnPAAm) and redox polymerization of NiPAAm or NnPAAm monomer using N,N′-methylenebisacrylamide as a crosslinker. There were a few differences in the swelling kinetics among these gels. However, a marked difference was observed in the shrinking processes, the rate of which was faster in the order of radiation-crosslinked PNiPAAm gel > radiation-crosslinked PNnPAAm gel > chemically crosslinked PNnPAAm gel > chemically crosslinked PNiPAAm gel. This difference was discussed in terms of the microscopic structure of the gels, which was studied by light scattering techniques. It was found that the static inhomogeneities frozen in the chemically and radiation-crosslinked gels play a key role in their shrinking kinetics.     

Solvent induced amplification of the photoresponsive properties of α,ω-di-[4-cyanophenyl-4'-(6-hexyloxy)-azobenzene]-poly(N-isopropylacrylamide) in aqueous media

Irradiation at room temperature of α,ω-di-[4-cyanophenyl-4'-(6-hexyloxy)-azobenzene]-poly-(N-isopropylacrylamide) (Az(2)-PNIPAM) solutions in water/1,4-dioxane (6 mol% dioxane) reversibly converts a turbid suspension into a clear solution, demonstrating for the first time that cononsolvency of PNIPAM in mixed aqueous solvents in synergy with preferential chromophore solvation can act as actuators of responsive systems.     

Interactions of sodium dodecyl sulfate with acrylamide –N-isopropylacrylamide) statistical copolymer

 Poly(N-isopropylacrylamide) (PNIPAM) precipitates out of water around 32 °C. This critical temperature is raised when hydrophilic acrylamide sequences are present on the polymer chain. We have used neutron scattering to study the structural properties of a statistical copolymer containing acrylamide and N-isopropylacrylamide segments at different temperatures and its interactions with an anionic surfactant, sodium dodecyl sulfate (SDS). At low temperatures, the copolymer behaves as a swollen polymer coil. With an increase in temperature, intermolecular attractions are observed, and close to the critical temperature of the copolymer, microphase separation is observed. Here, the structure consists of dense nodules of hydrophobic sequences stabilized by hydrophilic sequences. In the presence of a small amount of SDS, additional colloidal stability is observed: the nodule size is decreased. At high SDS concentration, the copolymer is completely solubilized at all temperatures studied and the structure of the polymer–surfactant complex resembles the “necklace” structure obtained for the homopolymer PNIPAM–SDS system. Received: 11 November 1999 Accepted: 15 December 1999     

Thermosensitive injectable hydrogels from poly(N-isopropylacrylamide)–dextran aqueous solutions: Thermogelation and drug release properties

Novel injectable thermosensitive hydrogel formulations with improved both water retention (WR) and drug release profile were prepared by adding dextran (DXT) to poly(N-isopropylacrylamide) (PNIPAM) aqueous solutions as a remedy against the demixing/syneresis phenomenon. The addition of the hydrophilic polysaccharide improved the WR of the hydrogel at 37°C from about 12% in the absence of DXT to about 40–55% out of the initial amount introduced, depending on both PNIPAM and DXT concentrations. Also, the 5-fluorouracil release experiments showed an appreciably reduced “burst effect” for the DXT-containing hydrogels. The shape of the release profiles revealed the presence of two stages, differing each other from the point of view of the drug release rate.     

Confinement Effects on the Crystallization Kinetics and Self-Nucleation of Double Crystalline Poly(p-dioxanone)-b-poly(ϵ-caprolactone) Diblock Copolymers

The morphology, crystallization and self nucleation behavior of double crystalline diblock copolymers of poly(p-dioxanone) (PPDX) and poly(ϵ-caprolactone) (PCL) with different compositions have been studied by different techniques, including optical microscopy (OM), atomic force microscopy (AFM) and differential scanning calorimetry (DSC). The two blocks crystallize in a single coincident exotherm when cooled from the melt. The self-nucleation technique is able to separate into two exotherms the crystallization of each block. We have gathered evidences indicating that the PPDX block can nucleate the PCL block within the copolymers regardless of the composition. This effect is responsible for the lack of homogeneous nucleation or fractionated crystallization of the PCL block even when it constitutes a minor phase within the copolymer (25% or less). Nevertheless, we were able to show that decreasing amounts of PCL within the diblock copolymer still produces confinement effects that retard the crystallization kinetics of the PCL component and decrease the Avrami index. On the other hand evidence for confinement was also obtained for the PPDX block, since as its content is reduced within the copolymer, a depression in its self-nucleation and annealing temperatures were observed.