With diabetes mellitus becoming an important public health concern, insulin‐delivery systems are attracting increasing interest from both scientific and technological researchers. This feature article covers the present state‐of‐the‐art glucose‐responsive insulin‐delivery system (denoted as GRIDS), based on responsive polymer materials, a promising system for self‐regulated insulin delivery. Three types of GRIDS are discussed, based on different fundamental mechanisms of glucose‐recognition, with: a) glucose enzyme, b) glucose binding protein, and c) synthetic boronic acid as the glucose‐sensitive component. At the end, a personal perspective on the major issues yet to be worked out in future research is provided. 相似文献
The insulin therapy constitutes the preferred treatment for Diabetes Mellitus (DM). The traditional insulin therapy, which consists of daily subcutaneous insulin injections to control blood glucose level, is not able to regulate the blood glucose level precisely. In this research, to facilitate the diabetic patient life, an intelligent drug delivery system based on a biodegrable biopolymer to control the insulin release, was designed. In this system, chitosan‐polyethylene glycol hydrogel and glucose oxidize play the role of drug carrier and glucose biosensor, respectively. To increase the hydrogel drug loading capacity, hydrogels with different PEG content were synthesized and insulin was loaded by swelling‐diffusion method into them. The loaded hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), High performance liquid chromatography (HPLC), and Thermogravimetric analysis (TGA). Finally, the thermodynamic study for insulin loading process was performed to investigate the stability of the drug in the system. 相似文献
Herein, we report a new drug‐delivery system (DDS) that is comprised of a near‐infrared (NIR)‐light‐sensitive gold‐nanorod (GNR) core and a phase‐changing poly(ε‐caprolactone)‐b‐poly(ethylene glycol) polymer corona (GNR@PCL‐b‐PEG). The underlying mechanism of the drug‐loading and triggered‐release behaviors involves the entrapment of drug payloads among the PCL crystallites and a heat‐induced phase change, respectively. A low premature release of the pre‐loaded doxorubicin was observed in PBS buffer (pH 7.4) at 37 °C (<10 % of the entire payload after 48 h). However, release could be activated within 30 min by conventional heating at 50 °C, above the Tm of the crystalline PCL domain (43.5 °C), with about 60 % release over the subsequent 42 h at 37 °C. The NIR‐induced heating of an aqueous suspension of GNR@PCL‐b‐PEG under NIR irradiation (802 nm) was investigated in terms of the irradiation period, power, and concentration‐dependent heating behavior, as well as the NIR‐induced shape‐transformation of the GNR cores. Remotely NIR‐triggered release was also explored upon NIR irradiation for 30 min and about 70 % release was achieved in the following 42 h at 37 °C, with a mild warming (<4 °C) of the surroundings. The cytotoxicity of GNR@PCL‐b‐PEG against the mouse fibroblastic‐like L929 cell‐line was assessed by MTS assay and good compatibility was confirmed with a cell viability of over 90 % after incubation for 72 h. The cellular uptake of GNR@PCL‐b‐PEG by melanoma MEL‐5 cells was also confirmed, with an averaged uptake of 1250(±110) particles cell?1 after incubation for 12 h (50 μg mL?1). This GNR@PCL‐b‐PEG DDS is aimed at addressing the different requirements for therapeutic treatments and is envisaged to provide new insights into DDS targeting for remotely triggered release by NIR activation. 相似文献
We developed a carbohydrate sensing material, which consists of a crystalline colloidal array (CCA) incorporated into a polyacrylamide hydrogel (PCCA) with pendent boronic acid groups. The embedded CCA diffracts visible light, and the PCCA diffraction wavelength reports on the hydrogel volume. This boronic acid PCCA responds to species containing vicinal cis diols such as carbohydrates. This PCCA photonic crystal sensing material responds to glucose in low ionic strength aqueous solutions by swelling and red shifting its diffraction as the glucose concentration increases. The hydrogel swelling results from a Donnan potential due to formation of boronate anion; the boronic acid pK(a) decreases upon glucose binding. This sensing material responds to glucose and other sugars at <50 microM concentrations in low ionic strength solutions. 相似文献
DNA‐tethered poly‐N‐isopropylacrylamide copolymer chains, pNIPAM, that include nucleic acid tethers have been synthesized. They are capable of inducing pH‐stimulated crosslinking of the chains by i‐motif structures or to be bridged by Ag+ ions to form duplexes. The solutions of pNIPAM chains undergo crosslinking at pH 5.2 or in the presence of Ag+ ions to form hydrogels. The hydrogels reveal switchable hydrogel‐to‐solution transitions by the reversible crosslinking of the chains at pH 5.2 and the separation of the crosslinking units at pH 7.5, or by the Ag+ ion‐stimulated crosslinking of the chains and the reverse dissolution of the hydrogel by the cysteamine‐induced elimination of the Ag+ ions. The DNA‐crosslinked hydrogels are thermosensitive and undergo reversible temperature‐controlled hydrogel‐to‐solid transitions. The solid pNIPAM matrices are protected against the OH? or cysteamine‐stimulated dissociation to the respective polymer solutions. 相似文献
A novel polymer complex system sensitive to glucose was studied as a candidate material for formulating a chemically regulated insulin release system. A ternary copolymer of N-vinyl-2-pyrrolidone (NVP), 3-acrylamidophenylboronic acid (AAm-PBA) and N,N-dimethylaminopropylacrylamide (DMAPAA) (poly(NVP-co-PBA-co-DMAPAA)) was synthesized by radical copolymerization. The phenylboronic acid group in this copolymer serves as a glucose sensor moiety. Poly(NVP-co-PBA-co-DMAPAA) was soluble in water in the pH range of 3–12, in sharp contrast to a binary copolymer of NVP and AAm-PBA (poly(NVP-co-PBA)) which showed solubility only under alkaline aqueous conditions, where the boronic acid group is in a tetrahedral ionized form. The protonated amino group in poly(NVP-co-PBA-DMAPAA) contributed to increase the solubility of the polymer under physiological and acidic aqueous conditions. Furthermore, poly(NVP-co-PBA-co-DMAPAA) formed a stable polymer complex gel with poly(vinyl alcohol) (PVA) in pH 7.4 phosphate buffered solution due to the formation of a covalent linkage between the boronic acid groups in ternary copolymer and diol units in PVA. The release of myoglobin as model protein from the complex gel was increased immediately after the addition of glucose, due to the transition of gel into sol state, indicating the feasibility of this complex gel as a candidate material for a glucose-responsive delivery system for insulin. 相似文献
Hydrogel formation triggered by a change in temperature is an attractive mechanism for in situ gelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A blocks (~22 kDA) but differing PEG-midblock lengths (2, 4 and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDA). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potential in situ gelling biodegradable materials for macromolecular drug delivery. 相似文献
The synthesis of a novel photoreactive poly(ethylene glycol) (PEG)‐based polymer with caged carbonyl groups is reported. We further demonstrate its use for the on‐demand fabrication of hydrogels. For rapid gelation, a hydrazide‐functionalized PEG is used as the second component for the hydrogel preparation. The photoreactive PEG‐based polymer is designed for controlled cleavage of the protecting groups upon exposure to UV light releases free aldehyde moieties, which readily react with hydrazide groups in situ. This hydrogel system may find applications in controlled release drug delivery applications, when combined with in situ gelation. Furthermore, the possibility of forming gels specifically upon UV irradiation gives an opportunity for 3D fabrication of degradable scaffolds.
In the present work a self‐regulated insulin delivery system based on the hydrogel poly(2‐hydroxyethyl methacrylate‐co‐N,N‐dimethylaminoethyl methacrylate) with entrapped glucose oxidase, catalase and insulin was developed and evaluated both by in vitro and in vivo studies. The hydrogels were characterized by FTIR, DSC, SEM and elemental analysis. The swelling studies were carried out in different pH and glucose solutions. The mesh size of the hydrogels and diffusion coefficient of water and insulin in different glucose solution was calculated. The effect of the crosslinking agent (ethylene glycol dimethacrylate) concentration (0–2% w/w) on swelling and insulin release was studied. The equilibrium swelling and insulin release was found to depend on the external glucose concentration and dimethylaminoethyl methacrylate content of the hydrogels. The in vivo studies indicated that the entrapped insulin was stable and was effective in reducing the blood glucose of streptozotocin induced diabetic rats. The histopathological studies revealed that there was no fibrous tissue encapsulation after 56 days of implantation. 相似文献
A pyrene‐containing phenylboronic acid (PBA) functionalized low‐molecular‐weight hydrogelator was synthesized with the aim to develop glucose‐sensitive insulin release. The gelator showed the solvent imbibing ability in aqueous buffer solutions of pH values, ranging from 8–12, whereas the sodium salt of the gelator formed a hydrogel at physiological pH 7.4 with a minimum gelation concentration (MGC) of 5 mg mL?1. The aggregation behavior of this thermoreversible hydrogel was studied by using microscopic and spectroscopic techniques, including transmission electron microscopy, FTIR, UV/Vis, luminescence, and CD spectroscopy. These investigations revealed that hydrogen bonding, π–π stacking, and van der Waals interactions are the key factors for the self‐assembled gelation. The diol‐sensitive PBA part and the pyrene unit in the gelator were judiciously used in fluorimetric sensing of minute amounts of glucose at physiological pH. The morphological change of the gel due to addition of glucose was investigated by scanning electron microscopy, which denoted the glucose‐responsive swelling of the hydrogel. A rheological study indicated the loss of the rigidity of the native gel in the presence of glucose. Hence, the glucose‐induced swelling of the hydrogel was exploited in the controlled release of insulin from the hydrogel. The insulin‐loaded hydrogel showed thixotropic self‐recovery property, which hoisted it as an injectable soft composite. Encouragingly, the gelator was found to be compatible with HeLa cells. 相似文献