酸化凹凸棒石/海藻酸复合材料的制备及其缓释性能

以海藻酸钠 (SA) 和酸化凹凸棒石 (H⁺-ATP) 为原料,运用溶液共混法制备了一种具有优良缓释性能的复合材料,并以其为基质材料制备了双氯芬酸钠 (DS) 缓释片.利用SEM、FTIR和XRD对复合材料形貌和结构进行了表征,考察了酸改性剂浓度、H⁺-ATP用量和复合时间对复合材料缓释性能的影响,以获得最佳复合工艺.结果表明,当用12 mol·L^-1盐酸酸化的ATP量占复合物总量60%时,复合缓释片在体外模拟肠液中缓释性能最佳.与单一海藻酸缓释片相比,复合缓释片2 h的累积释放率由42.6%下降到23.7%,有效改善了"突释"效应.释放动力学研究表明,复合缓释片的释药行为可以用Ritger-Peppas方程很好地拟合,释药速率受骨架溶蚀和药物扩散双重控制.H⁺-ATP的加入显著改善了海藻酸的缓释性能.     

羟丙基壳聚糖/氧化甲基纤维素自愈合水凝胶的制备及其载药性能

采用高碘酸钠对甲基纤维素（MC）进行氧化制备了氧化甲基纤维素（DAMC），通过羟丙基壳聚糖（HPC）的氨基与DAMC的醛基发生希夫碱反应制备了HPC/DAMC自愈合水凝胶。通过调节HPC和DAMC含量探究水凝胶的微观形态、溶胀性能、力学性能、自愈合性能、体外降解以及药物缓释性能。结果表明，HPC/DAMC自愈合水凝胶具有相互连通的孔隙，且孔径处于80～375μm范围内，在室温无刺激条件下能够在20 min内实现自愈合且具有良好的拉伸性能。此外，HPC/DAMC自愈合水凝胶具有良好的保水性，其溶胀比为14.0～17.4。在溶菌酶的作用下，HPC/DAMC自愈合水凝胶在60 h时质量损失率可达84.2%～99.6%。HPC/DAMC自愈合水凝胶对抗肿瘤药物吉西他滨具有缓释效果，缓释作用长达96 h，药物累积释放率达到83.2%～92.7%。     

Hydrogel capsules for sustained drug release

Interpenetrating polymer networks (IPNs) based on polyacrylamide and polyvinyl alcohol for hydrogel capsules were synthesized. These polymer networks were evaluated as drug-delivery devices using Crystal Violet and Bromothymol Blue as model drugs. The observed drug release is higher for semi-II-IPN than full-IPN. The drug-release behaviors from these capsules were analyzed by the exponent relation Mt/Mα = Ktⁿ, where “K” and “n” are constants and Mt/Mα is the fraction of the drug released until time “t.” The constant “n” was found to be above 0.5, which suggests that the release of drug from the capsules follows the non-Fickian diffusional model. The mechanical behavior of hydrogel disks were also analyzed. © 1994 John Wiley & Sons, Inc.     

Swelling and drug release behavior of calcium alginate/poly (sodium acrylate) hydrogel beads

In the present work calcium alginate/poly (sodium acrylate) composite beads have been prepared by in situ formation of cross-linked poly (sodium acrylate) network, within the calcium alginate (CA) beads. The CA/poly (SA) beads have been found to be stable for more than 48 h, in the physiological fluid (PF) of pH 7.4, while the plain alginate beads disintegrated within a couple of hours. The water uptake of beads was investigated under various composition parameters such as the amount of alginate, concentration of ionic cross-linker Ca⁺⁺ ions, monomer sodium acrylate (SA) contents, and degree of cross-linking. The beads also exhibited fair stability in the media of varying pH. Finally the release of model drug methylene blue (MB) was investigated. It was found that plain CA and CA/poly (SA) composite beads exhibited different release mechanisms.     

Formation of silk fibroin hydrogel and evaluation of its drug release profile

Silk hydrogels are interesting materials to be used as matrix in controlled drug delivery devices. However, methods to accelerate fibroin gelation and allow the drug incorporation during the hydrogel preparation are needed in literature. In this article we report the preparation of silk fibroin hydrogels with addition of several contents of ethanol, used to accelerate fibroin gelation kinetics, and we also evaluate the potential of these hydrogels to be used as matrices for drug delivery. Chemical and conformational properties did not change despite the amount of ethanol incorporated in the hydrogel. Hydrogels containing diclofenac sodium dissolved in ethanol showed a faster initial release of the drug than hydrogels with the drug dissolved in water but equilibrium was reached later. This indicates a more sustained drug delivery from hydrogels in which the model drug was dissolved in ethanol. Fibroin hydrogels confirm their promising use as biopolymeric matrices for controlled drug release. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41802.     

微颗粒水凝胶复合调驱体系的制备与性能评价

制备了一种新型微颗粒水凝胶堵剂,与驱油用表面活性剂复配后得到复合调驱体系,对该复合体系进行了室内性能评价,结果表明,该堵剂受地层水影响较小,且与驱油用表面活性剂复合稳定性良好。复合调驱体系耐温耐剪切性能良好,在地层温度条件下粒径增大,稳定性增强,界面张力达到6×10^(-3) mN/m,有利于实现驱油提采效果。且其注入性能良好,储层伤害低,可以实现深部调剖,对渗透率小于0.5μm(-3) mN/m,有利于实现驱油提采效果。且其注入性能良好,储层伤害低,可以实现深部调剖,对渗透率小于0.5μm²,孔径直径小于100μm的地层封堵性良好。同时该体系制备工艺、配液简单快速,大大降低了现场施工成本。为低成本高效调驱体系研发与应用提供了经验与方向。     

Controlled release study of carbaryl insecticide from calcium alginate and nickel alginate hydrogel beads

In this study, controlled release formulations for reducing environmental impact of pesticides have been produced by encapsulating as a model pesticide carbaryl (Carb) in the alginate beads. The various hydrogel bead formulations were prepared by the ionotropic crosslinking of sodium alginate (NaAlg) with calcium and nickel ions. The surface morphology of prepared beads was characterized with scanning electron microscopy (SEM). SEM confirmed the spherical nature and surface morphology of the particles. Bead characteristics, such as carbaryl entrapment efficiency, particle size, equilibrium swelling degree, and carbaryl release kinetics, were determined. The effects of the bead preparation conditions such as crosslinker concentration and type, carbaryl/sodium alginate (Carb/NaAlg) ratio and percentage of NaAlg on the carbaryl release from the calcium alginate (Ca‐Alg) and nickel alginate (Ni‐Alg) beads were investigated in distilled water at 25°C. It was observed that carbaryl release from the Ca‐Alg beads was slower than that of Ni‐Alg beads. The release results indicated that carbaryl release from both of the Ca‐Alg and Ni‐Alg beads decreases with the increasing crosslinker concentration, Carb/NaAlg ratio and percentage of NaAlg. The highest carbaryl release was found to be 100% for the Ni‐Alg beads at 3 days whereas the lowest carbaryl release was found to be 67% for the Ca‐Alg beads at 21 days. The swelling measurements of the beads were also in consistent with the carbaryl release results. The carbaryl release from most of the bead formulations followed Case II transport. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Preparation and evaluation of chitosan‐coated polyphosphazene hydrogel beads for drug controlled release

Chitosan‐coated polyphosphazene‐Ca²⁺ hydrogel beads were fabricated by dropping polyphosphazene into CaCl₂/chitosan gelling solution. Polyphosphazene used here was a water‐soluble degradable polyanion (PCPAP), which carried almost two carboxylatophenamino groups on each phosphorus atom of the polymer backbone. Two kinds of turbidimetric titration were applied in this study to reveal the interaction between PCPAP and chitosan within the pH range of 4.57≈7.14. The effect of gelling solution pH on the properties of chitosan‐coated PCPAP beads was especially emphasized. It was found that the PCPAP/chitosan complex prepared at relatively high pH (pH 6.5) dissociated most slowly in pH 7.4 phosphate‐buffered solution (PBS). The erosion of chitosan‐coated beads and the release of model drug (Coomassie brilliant blue and myoglobin) in PBS were both obviously prolonged with the increase of gelling solution pH, exhibiting perfect accordance with the behavior of complex dissociation. In addition, the coating of PCPAP/chitosan complex on the bead surface facilitated the improvement of drug loading efficiency. The higher the gelling solution pH, the more the drug loading efficiency improved. At pH 6.5 (PCPAP 5%, CaCl₂ 7%, chitosan 0.3%), the loading efficiency of myoglobin in beads reached as high as 93.2%. These results indicate that the chitosan‐coated polyphosphazene‐ Ca²⁺ bead is a potential formulation for drug controlled release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1993–1999, 2004     

A rechargeable drug delivery system based on pNIPAM hydrogel for the local release of curcumin

This study was designed to develop a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) hydrogel and a suitable solvent to enhance solubility and local release of curcumin. pNIPAM hydrogel was synthesized by radical polymerization. The chemical, mechanical and physical properties and biocompatibility of pNIPAM hydrogel were investigated as an implantable and rechargeable drug reservoir. Curcumin was loaded within pNIPAM hydrogel during swelling by using two different solvents; methanol, an organic solvent, and low molecular weight polyethylene glycol (PEG200), a polymeric solvent. The results of drug solubility showed that using PEG200 can increase curcumin solubility more than commonly used organic solvents such as methanol. Also, the release profile of drug-loaded hydrogels demonstrated that PEG200 has a superior effect on the cumulative amount of released curcumin (33.163 ± 0.319 μg/ml) compared to methanol (8.765 ± 0.544 μg/ml) during 1 week. Based on our results, curcumin-loaded hydrogels did not show any cytotoxicity, and pNIPAM/PEG combination represented an antibacterial effect within 12 hours. Accordingly, it can be concluded that pNIPAM hydrogel in combination with low molecular weight PEG200 could be used as an efficient drug delivery system to preserve and provide sustained release of curcumin as a hydrophobic drug.     

Fabrication of polymer/drug‐loaded hydroxyapatite particle composite fibers for drug sustained release

The aim of this study is to fabricate polymer/hydroxyapatite (HA) particle composite fibers for drug encapsulation and sustained release. Firstly, drug‐loaded hydroxyapatite particles are synthesized in one step, then by electrospinning of the blends of drug‐loaded hydroxyapatite particles and polymer solution the drug‐loaded polymer/hydroxyapatite particle composite fibers are successfully prepared. Effect of loading ratio of drug‐loaded hydroxyapatite particles in the fibers and pH value of the release medium on the drug release kinetics are both investigated, and the results demonstrate that, as compared with the polymer/drug electrospun fibers, the drug in the polymer/drug‐loaded hydroxyapatite particle composite fibers shows a sustained release manner, and the drug release rate can be regulated by both the loading ratio of drug‐loaded hydroxyapatite particles in the composite fibers and pH value of the buffer solution. The results indicate that the developed drug‐loaded polymer/hydroxyapatite particle composite fibers show great potential in bone regeneration and other related biomedical fields. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42871.     

Novel degradable polyphosphazene hydrogel beads for drug controlled release

Novel water‐soluble polyphosphazene containing carboxylatophenamino groups (PCPAP) was synthesized by the substitution reaction of ethyl p‐amino benzonate with poly(dichlorophosphazene), followed by alkali hydrolysis. Characterizations by IR, ¹H‐NMR, differential scanning calorimetry, and elemental analysis indicated that the reaction brought about an almost complete introduction of carboxylatophenamino to the polymer side chain. Calcium‐crosslinked PCPAP hydrogel beads were accomplished with an extremely mild method. The erosion experiments were conducted in vitro in various pH environments. The erosion duration of the beads at pH 7.4 and 37°C was effectively extended by an increase in the concentration of the PCPAP or CaCl₂ solution during the preparation process. Moreover, the bead erosion was sensitive to the pH. The sample dissolved 39.4% in a pH 8.0 buffer within 34 days but only 5.3% in a pH 5.0 buffer. Furthermore, PCPAP underwent degradation into macromolecular segments through the breaking of the backbone, and this could prevent accumulation in the body. These properties of PCPAP may be useful for controlled drug delivery, including intestine‐specific oral delivery systems. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 986–992, 2003     

Facile preparation and characterization of sodium alginate/graphite conductive composite hydrogel

Conductive composite hydrogels based on sodium alginate (SA) and graphite were fabricated by a facile method via dispersing homogeneously conductive graphite into SA hydrogel matrix. The hydrogel was formed by in situ release of Ca²⁺ from Ca–EDTA, thus eliminating the multistep reactions and tedious purification compared to the previous work. Raman spectra, scanning electron microscopy (SEM), X‐ray diffraction (XRD), and thermogravimetric analysis (TGA) were used to characterize the structure, crystalline nature, and thermostability of SA/graphite composite hydrogels. The SA/graphite composite hydrogels exhibited the improved network and layer‐type structure. The thermal stability of the hydrogel decreased slightly after the graphite was incorporated into the SA hydrogel matrix regardless of the content of graphite. The enhanced mechanical strength of SA/graphite composite hydrogel was achieved via increasing the f value (i.e., [Ca²⁺]/[COO^‐ in alginate]) and lowering graphite content. The conductivity of the composite hydrogels could be varied in a broad range, reaching up to 10⁻³ S/cm, mainly depending on the content of graphite and the f value. POLYM. COMPOS., 37:3050–3056, 2016. © 2015 Society of Plastics Engineers     

药物缓释用生物降解性高分子载体材料的研究

生物降解性聚合物安全、可靠,有良好的生物相容性,可通过生理途径代谢排出体外,成为了药物载体的首选材料。本文简要综述了主要常用天然和合成生物降解性聚合物,如壳聚糖、环糊精、胶原、聚乳酸、聚酸酐、氨基酸类聚合物的制备方法,在药物缓释体系的作用和效果,并对其发展趋势进行了展望。     

Electrospun hydroxypropyl methyl cellulose phthalate (HPMCP)/erythromycin fibers for targeted release in intestine

Ultrafine fiber mats of hydroxypropyl methyl cellulose phthalate (HPMCP) were successfully electrospun and explored as drug delivery vehicles using erythromycin as a model drug. The morphology of the electrospun fiber and the drug release process in the artificial gastric juice and in the artificial intestinal juice were investigated. With the same drug‐to‐matrix ratio (HPMCP/erythromycin = 9/1), all the fibers were electrospun into a tape‐like or ribbon shape and the average fiber diameter (AFD) was increased with the HPMCP concentration. Because of the pH‐sensitive property of HPMCP, erythromycin was released from the erythromycin‐containing electrospun HPMCP fiber mats by a slowly diffusion process in the artificial gastric juice, while it was released in nearly first‐order kinetics in the artificial intestinal juice because of the first‐order kinetics dissolution of the HPMCP fibers in the artificial intestinal juice. And the rate of erythromycin released in the artificial intestinal juice was about more than 2.5 times faster than that in the artificial gastric juice. The diameter of the fibers plays an important role on the rate and the total amount of the drug released both in stomach and in intestine, the rate and the total amount of the drug released decreasing with increasing AFD. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

pH-sensitive hydrogel based on carboxymethyl chitosan/sodium alginate and its application for drug delivery

Carboxymethyl chitosan sodium salt (CMCS)/sodium alginate (SA), a pH-sensitive hydrogel composed of CMCS and SA crosslinked by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide, has been evaluated in vitro as a potential carrier for protein drug delivery of bovine serum albumin (BSA). The crosslinked structures, pore morphologies, and mechanical properties of the composite CMCS/SA hydrogel at different pH have been characterized by Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and dynamic mechanical analysis (DMA). The swelling behavior of the prepared hydrogel was assessed at different pH values, 1.2, 4.0, 6.86, 7.4, and 9.0. The in vitro slow release ability of the CMCS/SA hydrogel was assessed at 37°C and pH 1.2 or pH 7.4 to simulate gastrointestinal and mouth environments in vivo. The efficiency was found to be greater than 90% at pH 7.4. The composite CMCS/SA hydrogel showed no cytotoxic effect toward L-929 cells according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. These findings demonstrate that the composite hydrogel has promising potential for drug delivery. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 46911.     

Core–shell biopolymer microspheres for sustained drug release

In this work, a core–shell biopolymer microsphere comprising a carvedilol‐loaded yeast cell wall polysaccharides core surrounded by a silk fibroin shell layer is developed to eliminate the risks of using synthetic polymers for drug encapsulation on human health and to avoid burst release and to prolong the release time. Transmission electron microscopy, Fourier‐transform infrared, confocal laser scanning microscope, and phase contrast microscopy analysis indicate that yeast treated with Tris–HCl containing cetyltrimethylammonium bromide, EDTA, and NaCl could provide much larger space for host drug as compared to plasmolyzed cells because the former can help maintain the original shape of yeast cells. In addition, its permeability barrier is significantly altered and nucleus becomes pyknotic. In contrast, plasmolyzed cells can hardly maintain the rigidity and integrity of their cell walls and will finally end up with cell fragments. SEM observation reveals that the carvedilol‐loaded cells maintain very similar shape and size before and after coating with 0.1% silk fibroin. In vitro release studies show that a drug delivery system using the carvedilol‐loaded cells can achieve a sustained drug release up to 20 days probably due to the electrostatic interaction between the positively charged carvedilol and the negatively charged yeast cells at the pH 7.4 and to the stability of the yeast cell helped by silk fibroin that provides an effective diffusion barrier. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41782.     

NIR光响应型PNIPAM/GO复合体系的制备及药物释放

多刺激合作响应的智能药物输送体系具有重要的研究价值。采用乳液聚合法将N-异丙基丙烯酰胺（NIPAM）与丙烯酸（AA）聚合为PNIPAM-co-AA微凝胶，并进一步与氧化石墨烯（GO）超声共混得到PNIPAM-co-AA/GO复合体系，将其应用于药物释放研究。采用FTIR、TEM、DLS、UV-Vis对微凝胶及复合体系的结构和性能进行表征。结果表明，PNIPAM-co-AA微凝胶的粒径约为458.7 nm，最低临界相转变温度（LCST）为40 ℃，具有温度敏感性和pH敏感性。在PNIPAM-co-AA微凝胶体系中引入GO后， GO的存在将复合体系的温度响应控制转化成了近红外（NIR）响应，结果表明，复合体系受到NIR光照射，可在3 min内将NIR光能转化为热能达到微凝胶的LCST，多次循环后光热转化性能稳定。药物释放实验结果表明，有NIR、pH 7.4条件下，5-氟尿嘧啶（5-FU）在24 h内的累积释放率最高为77.24%。     

In situ incorporation of monodisperse drug nanoparticles into hydrogel scaffolds for hydrophobic drug release

The effective and locally sustained delivery of hydrophobic drug with hydrogels as carriers is still a challenge owing to the inherent incompatibility of hydrophilic hydrogel network and hydrophobic drug. One promising approach is to use porous hydrogels to encapsulate and deliver hydrophobic drug in the form of nanoparticles to the disease sites. However, this approach is currently limited by the inability to load concentrated hydrophobic drug nanoparticles into the hydrogels because of the severe nanoparticle aggregation during the loading process. In this article, we firstly designed and fabricated efficient drug nanoparticles embedded hydrogels for hydrophobic drug delivery by incorporating monodisperse silybin (hydrophobic drug for liver protection) nanoparticles into acrylated hyaluronic acid (HA‐AC) based hydrogels through in situ cross‐linking. The silybin nanoparticles embedded hydrogel scaffolds proved to be a good sustained release system with a long period of 36 h. The drug release from this hybrid hydrogels could be modulated by tuning HA‐AC concentration, cross‐linking ratio, chain length of cross‐linker and drug loading amount. The different kinetic models were applied, and it was observed that the release profile of silybin best followed the Hixson‐Crowell model for the release of drug from the hydrogels embedding silybin nanoparticles. It could be envisioned that this process would significantly advance the potential applications of hydrogel scaffolds mediated hydrophobic drug delivery in clinical therapies. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43111.     

Preparation and characterization of a positive thermoresponsive hydrogel for drug loading and release

A positive thermoresponsive hydrogel composed of poly(acrylic acid)‐graft‐β‐cyclodextrin (PAAc‐g‐β‐CD) and polyacrylamide (PAAm) was synthesized with the sequential interpenetrating polymer network (IPN) method for the purpose of improving its loading and release of drugs. The structure and properties of the PAAc‐g‐β‐CD/PAAm hydrogel (IPN hydrogel) were characterized with Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and swelling measurements. FTIR studies showed that the IPN hydrogel was primarily composed of an IPN of PAAc‐g‐β‐CD and PAAm. The data from DSC and swelling measurements indicated that the phase‐transition temperature or upper critical solution temperature (UCST) of the IPN hydrogel was approximately 35°C. Through the measurement of the temperature dependence of the swelling, increases in the UCST and non‐sensitivity to changes in the salt concentration were observed for the IPN hydrogel versus the normal IPN hydrogel poly(acrylic acid)/PAAm (without β‐cyclodextrin). Furthermore, the swelling/deswelling kinetics of the IPN hydrogel also exhibited an improved controllable response rate versus the normal IPN hydrogel. Ibuprofen (IBU) was chosen as the model drug for examining loading and release from the IPN hydrogel. The experimental data proved that the IPN hydrogel provided a positive drug release pattern; the IBU released faster at 37°C than at 25°C, and improved drug loading and controlled release were achieved by the IPN hydrogel versus the normal IPN hydrogel. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009