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Biodegradable injectable polymer (IP) systems exhibiting temperature-responsive sol-to-gel transitions between room temperature and body temperature have the potential for use in biomedical applications. However, gelation of such IP systems is a reversible process through physical cross-linking, and the hydrogels thus formed are likely to revert to the sol state under highly wet conditions after injection. In this study, a biodegradable IP system exhibiting temperature-responsive irreversible sol-to-gel transition by covalent bond formation was developed by simple mixing of polymers. A triblock copolymer of poly(caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG) and tri-PCG with attached succinimide ester groups at both termini (tri-PCG-SA-OSu) were prepared and mixed together with a water-soluble polyamine (typically poly-l-lysine). The obtained IP formulation was in the sol state after mixing, but exhibited a rapid sol-to-gel transition within 30 s upon increasing the temperature to 37 °...

Metal fluorides are gathering significant interest for use in many applications, such as optical glasses, chemical sensors, and solid electrolytes using fluoride ion batteries, due to their high transparency over a wide wavelength range (ultraviolet to infrared) and fast fluoride ion conductivity. Here, we present a topotactic route for synthesizing thin films of fluorite-type Ba0.5Bi0.5F2.5 (BBF), a promising fluoride ion conductor, from perovskite-type BaBiO3 (BBO) precursor films by fluorination using poly(vinylidene fluoride). The fluorination reaction fully converted BBO to BBF without stopping at the oxyfluoride stage. The BBF films obtained at relatively low reaction temperatures (150–200 °C) showed Ba/Bi cation ordering in the [001] direction, indicating that the cation framework of perovskite BBO was maintained during the fluorination reaction. Meanwhile, increasing the fluorination temperature led to mixtures of cations, resulting in random distribution of Ba and Bi. This demonstrates that the d...

Amphiphilic triblock copolymers of poly(ethylene glycol) (PEG) and aliphatic polyesters such as poly(ɛ-caprolactone-co-glycolide) (PCGA) are typical examples of thermogelling polymers. In the gelation mechanism of these polymers, polymer chain transfer between the micelles, and subsequent aggregation of the micelles are important steps. We previously reported IP systems exhibiting temperature-responsive irreversible sol-gel transition that formed covalently cross-linked hydrogels. The IP formulation prepared by the ‘freeze–dry with PEG/dispersion’ method (D-sample) retained its sol state at r.t. longer than a formulation prepared by the usual dissolution method (S-sample). We hypothesized that polymer chain transfer between micelles was suppressed in the D-samples, because the micelle cores were in a solid-like state. In this study, we investigated polymer chain transfer by the fluorescence resonance energy transfer (FRET) method to reveal its role in the sol-to-gel transition. We synthesized a triblock copolymer of PCGA and PEG (tri-PCG) with attached naphthalene or dansyl groups at termini, tri-PCG-nap and tri-PCG-dan, as FRET donors and acceptors, respectively. The FRET behavior of the mixture of tri-PCG-nap/tri-PCG micelles and tri-PCG-dan/tri-PCG micelles was investigated. It was revealed that polymer chain transfer between micelles was strongly accelerated at the gelation temperature, and polymer chain transfer in D-samples was suppressed compared to S-samples. On the gelation of thermogelling polymer solutions, polymer chain transfer between the micelles and subsequent aggregation of the micelles are important steps. In this study, we investigated polymer chain transfer by the fluorescence resonance energy transfer (FRET) method to reveal its role in the sol-to-gel transition. We synthesized amphiphilic triblock copolymer attaching naphthalene or dansyl groups at termini, tri-PCG-nap and tri-PCG-dan. The FRET behavior of the mixture of tri-PCG-nap/tri-PCG micelles and tri-PCG-dan/tri-PCG micelles was investigated.

Here, we report biodegradable temperature-triggered covalent gelation systems exhibiting a longer and controllable duration time of the gel state by a “mixing strategy” utilizing a thiol–ene reaction. We synthesized a tri-block copolymer of poly(caprolactone-co-glycolic acid) and PEG (tri-PCG) as a temperature-responsive injectable polymer (IP) and attached acryloyl groups on both termini (tri-PCG-Acryl). A tri-PCG micelle solution containing hydrophobic hexa-functional polythiol (Solution-A) and a tri-PCG-Acryl micelle solution (Solution-B) were mixed together. After mixing, the solution was still in the sol state at r.t., but exhibited an irreversible sol-to-gel transition in response to temperature. The duration time of the gel state while soaking in PBS could be altered from 1 day to 93 days by changing the mixing ratio of Solution-A/B. The physical strengths of the hydrogels were also controllable by changing the mixing ratio. The IP system showed good biocompatibility and a long duration time of the gel state after subcutaneous implantation.

On clinical application of biodegradable injectable polymer (IP) systems, quick extemporaneous preparation of IP formulations and longer duration time gel state after injection into the body are the important targets to be developed. Previously, we had reported temperature-responsive covalent gelation systems via bio-orthogonal thiol-ene reaction by ‘mixing strategy’ of amphiphilic biodegradable tri-block copolymer (tri-PCG) attaching acryloyl groups on both termini (tri-PCG-Acryl) with reactive polythiol. In other previous works, we found ‘freeze-dry with PEG/dispersion’ method as quick extemporaneous preparation method of biodegradable IP formulations. In this study, we applied this quick preparative method to the temperature-triggered covalent gelation system. The instant formulation (D-sample) could be prepared by ‘freeze-dry with PEG/dispersion’ just mixing of tri-PCG-Acryl micelle dispersion and tri-PCG/DPMP micelle dispersion with PEG, that can be prepared in 30 s from the dried samples. The obtained D-sample showed irreversible gelation and long duration time of gel state, which was basically the same as the formulations prepared by the usual heating dissolution method (S-sample). Interestingly, the D-sample could maintain its sol state for a longer time (24 h) after preparing the formulation at r.t. compared with the S-sample, which became a gel in 3 h after preparing. The IP system showed good biocompatibility and long duration time of the gel state after subcutaneous implantation. These characteristics of D-samples, quick extemporaneous preparation and high stability in the sol state before injection, would be very convenient in a clinical setting.

Aqueous solutions of biodegradable polymers exhibiting sol-to-gel transitions in response to external stimuli such as temperature and pH are expected to be used as injectable polymers (IPs) for biomedical applications. In this study, we prepared novel biodegradable temperature-responsive IP systems providing variable gel-forming pH regions. We synthesized PCGA-b-PEG-b-PCGA (tri-PCG) and attached carboxylic acid or primary amine groups on both termini, tri-PCG-COOH and tri-PCG-NH2, and investigated the temperature-responsive sol-to-gel transition behavior of the mixtures of these two copolymers at various pHs. We found that the gel-forming pH region of the mixed system could be easily controlled by simply changing the mixing ratios of these polymers.

We investigated the release behavior of glucagon-like peptide-1 (GLP-1) from a biodegradable injectable polymer (IP) hydrogel. This hydrogel shows temperature-responsive irreversible gelation due to the covalent bond formation through a thiol-ene reaction. In vitro sustained release of GLP-1 from an irreversible IP formulation (F(P1/D+PA40)) was observed compared with a reversible (physical gelation) IP formulation (F(P1)). Moreover, pharmaceutically active levels of GLP-1 were maintained in blood after subcutaneous injection of the irreversible IP formulation into rats. This system should be useful for the minimally invasive sustained drug release of peptide drugs and other water-soluble bioactive reagents.

We investigated the polyvinylidene fluoride (PVDF)-mediated topotactic fluorination of two perovskite ruthenate thin films with different crystallographic structures, non-layered perovskite SrRuO3 and layered perovskite Sr2RuO4. While the former ruthenate did not react with PVDF, the latter was fluorinated to form Sr2RuO3F2 with a structure that exhibited a largely expanded c-axis. These results indicate that fluorine ions are preferentially inserted into the SrO rocksalt blocks in perovskite ruthenates, and that the oxygen atoms in the precursor oxide were partially removed upon fluorination. Finally, we noted that the Sr2RuO3F2 film was insulating, with a resistivity of 4.1 × 10 Ω cm at 300 K. It should be noted that this resistivity is five orders of magnitude higher than that of the metallic Sr2RuO4 film (6.7 × 10−4 Ω cm).