Thermogelling Poly Research Articles

Recyclable macromolecular thermogels for Hg(II) detection and separation via sol-gel transition in complex aqueous environments

The sensitive detection and quantitative separation of toxic heavy metal ions in aqueous media are of great importance. In this study, a thermogelling poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) triblock copolymer (P1) was synthesized, and difluoroboron dipyrromethene (BODIPY) fluorophore integrated with thiosemicarbazide units was attached to the chain ends of P1 through consecutive post-polymerization modifications, leading to P4. P4 exhibited rapid and selective detection of Hg(II) in 100% aqueous media via turn-on fluorescence emission with a limit of detection (LOD) of as low as 0.461 μM. This turn-on emission behavior is attributed to the suppression of C˭N isomerization caused by the formation of a coordination complex between P4 and Hg(II) ions. The selective and quantitative removal of Hg(II) among various metal ions was achieved by trapping chelated Hg(II) ions inside the dehydrated P4 gel via thermo-controlled sol-gel-dehydrated gel transitions. Treating the Hg(II) ion-trapped dehydrated gels with sodium sulfide (Na2S) in acetone/water at room temperature led to HgS precipitates, and P4 in solution was dried and recycled. This recyclable thermoresponsive macromolecular probe is promising for not only Hg(II) detection but also its separation and removal from complex aqueous environments.

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

A reactive oxygen species (ROS)-sensitive degradable polymer would be a promising material in designing a disease-responsive system or accelerating degradation of polymers with slow hydrolysis kinetics. Here, a thermogelling poly(ethylene glycol)-polycaprolactone-poly(ethylene glycol) (PEG-PCL-PEG or EG12 -CL20 -EG12 ) triblock copolymer with an oxalate group at the middle of the polymer is reported. The polymers form micelles with an average size of 100 nm in water. Thermogelation is observed in a concentration range of 8.0-37.0 wt%. In particular, the aqueous PEG-PCL-PEG triblock copolymer solutions are in a gel state at 37 °C in a concentration range of 25.0-37.0 wt%, whereas the aqueous PEG-PCL diblock copolymer solutions are in a sol state in the same concentration range at 37 °C. Thus, the gel depot could dissolve out once degradation of the triblock copolymers occurs at the oxalate group as confirmed by the in vitro experiment. In vivo gel formation is confirmed by injecting an aqueous PEG-PCL-PEG solution (36.0 wt%) into the subcutaneous layer of rats. The gel completely disappears in 21 d. A model polypeptide drug (cyclosporine A) is released over 21 d from the in situ formed gel. The micelle-based thermogel of PEG-PCL-PEG with ROS-triggering degradability is a promising injectable material for biomedical applications.

Poly(carbonate urethane)-Based Thermogels with Enhanced Drug Release Efficacy for Chemotherapeutic Applications.

In this study, we report the synthesis and characterisation of a thermogelling poly(carbonate urethane) system comprising poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG) and poly(polytetrahydrofuran carbonate) (PTHF carbonate). The incorporation of PTHF carbonate allowed for the control of the lower critical solution temperature (LCST) and decreased critical gelation concentration (CGC) of the thermogels significantly. In addition, the as-prepared thermogels displayed low toxicity against HepG2, L02 and HEK293T cells. Drug release studies were carried out using doxorubicin (Dox). Studies conducted using nude mice models with hepatocellular carcinoma revealed that the Dox-loaded poly(PEG/PPG/PTHF carbonate urethane) thermogels showed excellent in vivo anti-tumour performance and effectively inhibited tumour growth in the tested model.

An Injectable Thermogel Containing Levonorgestrel for Long-Acting Contraception and Fertility Control of Animals.

The demand of contraception and fertility control of animals is huge in livestock field and pet market. In this study, we suggest a formulation made up of an injectable and biodegradable thermogel for sustained delivery of levonorgestrel (LNG), a hormonal contraceptive, to realize the long-acting animal contraception. A thermogelling poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer was synthesized in a one-pot reaction. The micelles formed by the amphiphilic polymer carriers in water could serve as a reservoir for the solubilization of hydrophobic LNG molecules. The concentrated polymer aqueous solution exhibited a reversible sol-gel transition upon heating, and the incorporation of various amounts of LNG was found not to affect the thermogelation of the polymer/water system. In vitro release profiles showed that the entrapped LNG was sustainedly released from the thermogel matrix and the initial drug-loading amounts had a significant influence on the release kinetics of LNG. In vivo pharmacokinetic studies demonstrated that the use of PLGA-PEG-PLGA thermogel markedly extended the release of LNG after subcutaneous injection into SD rats. Consequently, this study revealed that the injectable PLGA-PEG-PLGA thermogel was a promising candidate for sustained delivery of LNG, and provided an attractive option for long-term contraception and fertility control of animals by a way of facile fabrication, easy administration and low expense.

Effects of Molecular Weight and Its Distribution of PEG Block on Micellization and Thermogellability of PLGA–PEG–PLGA Copolymer Aqueous Solutions

While amphiphilic block copolymers have been extensively investigated, little is known about the effect of molecular weight distribution (MWD) of the hydrophilic blocks on corresponding physical gelation behaviors. Herein, we employed thermogelling poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PLGA–PEG–PLGA) as the model system. We synthesized the block copolymer and prepared a series of copolymers with similar PLGA blocks but varied lengths and distributions of the PEG block. The micellization in dilute solutions was detected by light scattering and fluorescence spectroscopy using the probe 1-anilino-8-naphthalenesulfonate (ANS) specifically for the micelle coronae. Vial-inverting observations and rheological measurements were carried out to judge sol or gel states for the concentrated aqueous systems. The gel-to-sol transition or sol-to-gel transition occurred only with appropriate molecular weight (MW) and molar mass dispersity (ĐM). In this study, we denote t...

New thermogelling poly(ether carbonate urethane)s based on pluronics F127 and poly(polytetrahydrofuran carbonate)

ABSTRACTPluronics F127 or (PEG)99–(PPG)69–(PEG)99 (with PEG and PPG representing polyethylene glycol and polypropylene glycol, respectively) was chemically modified by reacting with poly(polytetrahydrofuran carbonate) (PTHF) diol using a standard poly(urethane) reaction. The poly(F127/PTHF urethane)s showed lower critical gelation concentration as compared with Pluronics F127. The solution properties of these polymers were investigated at different temperatures using a hydrophobic dye probe. The thermodynamic variables associated with micelle formation were determined. This study uncovered valuable structure–property relationships affecting the micellization and gelation behavior. We tested these materials as potential ophthalmic delivery agents for the sustained release of natamycin for the treatment of eye infections. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39924.

Thermogelling Chitosan-g-(PAF-PEG) Aqueous Solution As an Injectable Scaffold

The present study reports on a thermogelling poly(ethylene glycol)-poly(L-alanine-co-L-phenyl alanine) grafted chitosan (CS-g-(PAF-PEG)) system, focusing on phase diagram, transition mechanism, and in vivo gel duration. The sol-to-gel transition temperature decreased from 27 to 11 °C as the concentration increased from 4.0 wt % to 9.0 wt %. The polymer formed micelles with 10-50 nm in diameter at 10 °C and formed large aggregates ranging from hundreds to thousands of nanometers in size as the temperature increased from 10 to 35 °C, suggesting that an extensive molecular aggregation might be involved in the sol-to-gel transition. To study the transition mechanism on a molecular level, we investigated pH, circular dichroism spectra, and (13)C NMR spectra of the CS-g-(PAF-PEG) aqueous solution as a function of temperature. As the temperature increased, deprotonation of the chitosan and dehydration of the PEG were suggested, whereas the α-helical secondary structure of PAF was slightly changed in the sol-to-gel transition temperature range of 10-50 °C. A gel was formed in situ after injecting the CS-g-(PAF-PEG) aqueous solution into the subcutaneous layer of rats. About 60-70% of the gel was eliminated in 1 week, and the remaining gel was completely cleared from the implant site in 14 days. The results indicate the potential of CS-g-(PAF-PEG) as a promising short-term carrier for pharmaceutical agents.

Sustained delivery of paclitaxel using thermogelling poly(PEG/PPG/PCL urethane)s for enhanced toxicity against cancer cells

A multiblock poly(ether ester urethane)s comprising poly(ε-caprolactone), poly(ethylene glycol), and poly(propylene glycol) segments was synthesized. The aqueous copolymer solution exhibited thermogelling behavior at a critical gelation concentration of 3 wt %. The chemical structure and molecular characteristic of the copolymers were studied by gel permeation chromatography, NMR, and fourier transform infrared spectroscopy (FTIR). Rheological characterizations on the thermogel were carried out. Drug release studies using paclitaxel showed that sustained drug release of more than 2 weeks can be achieved with this system. The paclitaxel-loaded gels showed efficiency in the control of the growth of HeLa cells when compared with the paclitaxel dissolved in solution or paclitaxel encapsulated in Pluronics F127. The results demonstrated that the copolymers could be potentially used in chemotherapeutic applications.

New biocompatible thermogelling copolymers containing ethylene-butylene segments exhibiting very low gelation concentrations

We present a new thermogelling poly(ether urethane) consisting of poly(ethylene-butylene) (PEB), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments. Their aqueous solutions exhibited thermogelling behavior at critical gelation concentrations (CGC) ranging from 1.7 to 11.9 wt%. The composition and structural information of the copolymers were determined by GPC and 1H NMR. The critical micellization concentration (CMC) and thermodynamic parameters for micelle formation of these copolymers were determined at different temperatures by the dye absorption method. It was found that the incorporation of small quantities of PEB led to a significant decrease in the CGC of the thermogelling copolymers. Rheological characterization of the thermogels provided insight into the mechanical properties of the gel. The non-toxicity of the copolymer towards L929 mouse fibroblast cells provides us with great optimism in utilizing this material for biological or medical-based applications.

PVPylated Poly(alanine) as a New Thermogelling Polymer

In order to investigate poly(N-vinyl pyrrolidone) as an alternative to poly(ethylene glycol) in preparing a biomedical polymer, we synthesized a series of reverse thermogelling poly(N-vinyl pyrrolidone-b-alanine) (PVP-PA). The amphiphilic polymers consisting of the hydrophilic PVP block and the hydrophobic PA block formed micelles in water and the micelles aggregated as the temperature increased. FTIR spectroscopy, circular dichrosim spectroscopy, and 13C NMR spectroscopy showed that the aggregation behavior accompanied a change in PA conformation as well as a decrease in the molecular motion of PVP-PA. The sol-to-gel transition temperature decreased as the PA block length increased, PVP block length decreased, and l-alanine/dl-alanine ratio of PA increased. This paper suggests that PVP can be a promising alternative to poly(ethylene glycol) in designing a reverse thermogelling biomaterial.

A New Injectable Thermogelling Material: Methoxy Poly(ethylene glycol)–Poly(sebacic acid-D,L-lactic acid)–Methoxy Poly(ethylene glycol) Triblock Co-polymer

A novel injectable thermogelling poly(ester-anhydride) co-polymer, methoxy poly(ethylene glycol)–poly(sebacic acid-D,L-lactic acid)–methoxy poly(ethylene glycol) (mPEG–poly(SA-LA)–mPEG) triblock co-polymer, was prepared by melt-condensation polymerization. The synthesized triblock co-polymer was characterized by FT-IR and 1H-NMR. The aqueous solutions of mPEG–poly(SA-LA)–mPEG underwent sol–gel precipitation transition when the temperature was increased from 20 to 70°C, depending on the concentration of the polymer. 5-FU, as the model drug, was mixed into the gel in a low-viscous sol state at room temperature. About 63 wt% of the loaded 5-FU could be released in vitro from the gel over 72 h at 37°C. Subcutaneous injection of 25 wt% mPEG–poly(SA-LA)–mPEG aqueous solution resulted in the formation of a in situ gel depot in a rat model, which sustained for longer time than that of Pluronic F-127 aqueous solution. The biodegradable thermogelling mPEG–poly(SA-LA)–mPEG triblock co-polymer is believed to be a promising candidate for drug-delivery applications.

Temperature-Sensitive Poly(caprolactone-co-trimethylene carbonate)−Poly(ethylene glycol)−Poly(caprolactone-co-trimethylene carbonate) as in Situ Gel-Forming Biomaterial

We are reporting a new thermogelling poly(caprolactone-co-trimethylene carbonate)−poly(ethylene glycol)−poly(caprolactone-co-trimethylene carbonate) (PCTC−PEG−PCTC) triblock copolymer. By incorporating the comonomer (trimethylene carbonate) up to 25−40 wt % in the polycaprolactone block, the resulting PCTC−PEG−PCTC triblock copolymer achieved sol stability while keeping the thermogelling property in a physiologically important temperature range of 10−50 °C. The precipitation of the polymer in water at 20 °C was a concern for a poly(caprolactone)−poly(ethylene glycol)−poly(caprolactone) (PCL−PEG−PCL) system for practical applications (Macromolecules 2006, 39, 4873). The PCTC−PEG−PCTC triblock copolymer thermogel did not show the characteristic peaks of the polycaprolactone crystalline domain at 2θ = 21.5° and 23.5° in the X-ray diffraction spectra. The sol-to-gel transition temperature of PCTC−PEG−PCTC aqueous solution could be controlled in a range of 15−30 °C by varying the composition and molecular weight of PCTC. The PCTC−PEG−PCTC was not degraded in a phosphate buffer saline for 50 days, whereas significant changes in molecular weight and composition of the polymer were observed for the polymer implanted in the subcutaneous layer of rats over the same period of time. The in situ formed hydrogel of PCTC−PEG−PCTC was investigated as a three-dimensional cell culture medium. Compared with the traditional culture on a plate (two-dimensional culture), the chondrocytes cultured in the in situ formed PCTC−PEG−PCTC hydrogel (three-dimensional culture) showed a higher expression of collagen type II and aggrecan and suppression of collagen type I (fibroblastic gene), suggesting the excellent differentiation of the cell in the PCTC−PEG−PCTC hydrogel.

Thermogelling Poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) Disulfide Multiblock Copolymer as a Thiol-Sensitive Degradable Polymer

We report a reverse thermogelling poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) disulfide multiblock copolymer as a thiol-sensitive biodegradable polymer. The poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) aqueous solutions studied in this research underwent sol-gel-sol or sol-gel-sol-gel transition depending on the molecular weight and concentration of the polymer, whereas the corresponding disulfide multiblock copolymer aqueous solutions underwent sol-gel transition as the temperature increased in a range of 0-60 degrees C. The hydrophobic dye solubilization and dynamic light scattering of the polymer aqueous solution suggest that the poly(ethylene oxide-b-propylene oxide-b-ethylene oxide)s undergo unimer (3 nm) to micelle (12 nm) transition, whereas the disulfide multiblock copolymers undergo unimer (6 nm) to aggregated polymer (600 nm) transition as the temperature increases. The gel duration increased from 6 h (poly(ethylene oxide-b-propylene oxide-b-ethylene oxide)) to more than 12 days (the corresponding disulfide multiblock copolymer) in phosphate buffer saline, and the gel duration of the latter depended on the glutathione concentration of the medium. The model drug, paclitaxel, was released from the in-situ-formed poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) disulfide multiblock copolymer gel in a glutathione concentration-sensitive manner.

New thermogelling poly(organophosphazenes) with methoxypoly(ethylene glycol) and oligopeptide as side groups

A new class of thermogelling poly(organophosphazenes) bearing a hydrophilic methoxypoly(ethylene glycol) (MPEG) and a hydrophobic tri or tetrapeptide such as GlyPheLeuEt, GlyPheIleEt, GlyLeuPheEt, and GlyPheLeuGlyEt have been synthesized and characterized by means of multinuclear ( 1H, 31P) NMR spectroscopy, gel permeation chromatography, viscometry, and elemental analysis. The gelation of the present polymers is presumed to be attributed to the intermolecular interaction between the hydrophobic oligopeptide side groups, which can form strong physical junction zones in the polymer aqueous solution. The gelation properties of the polymer were affected by the subtle change in the nature of the hydrophobic oligopeptide, composition of the hydrophilic to hydrophobic side groups, and the concentration of the polymer solutions. Among the present thermogels, the copolymer with equimolar MPEG and GlyPheIleEt as side groups showed the excellent gel phase persisting over 35–43 °C, which indicates that it is a new promising material for drug delivery and tissue engineering.