介孔羟基磷灰石的合成及药物释放性能研究

本文采用水热合成法,制备出介孔羟基磷灰石,该材料具有较高比表面积和较大的孔容,药物缓释性能测试表明,材料具有较高的药物组装率和较好药物缓释性能,因此,可以作为药物缓释载体,从而更好地实现对骨组织的修复。     

Polyphophazenes as anti-cancer drug carriers: From synthesis to application

Currently, most of administered anti-cancer drugs are low molecular weight compounds (as compare to polymers) and hydrophobic in nature. Such small molecular anti-cancer drugs possess fast clearance rate from the blood circulating system and have toxic side effects. Poly(organophosphazenes) have wide range of biomedical applications owing good biocompatibility, sustainability and degradability into non-toxic by-products. So, in this review, we have carefully selected such poly(organophosphazenes), which proved to be good anti-cancer drug carriers because of overcoming crucial issues related to the administration of anti-cancer drugs i.e. poor hydrophilicity, lack of cancer cells specificity, and fast clearance rate from blood circulating system. Thence, the main focus of this review is to highlight the advancement that have been achieved in the synthesis of poly(organophosphazenes) and their application in anti-cancer drug delivery system (DDS).     

温敏聚N-异丙基丙烯酰胺的载药和释药性能研究

以对乙酰氨基酚为模型药物分子,温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm)为载体,研究了药物在凝胶上的负载和在不同温度(25和37℃)下磷酸盐缓冲溶液(pH 7.4)中的释放行为.结果表明,对乙酰氨基酚的负载量约为35wt％,并且与载体PNIPAAm存在氢键作用.药物在磷酸盐缓冲溶液中的体外模拟释放结果显示,当温度(37℃)高于凝胶的LCST时,对乙酰氨基酚释放的较慢;当温度(25℃)低于其LCST时,释放的较快.因此,可通过环境温度的改变达到APAP在载体PNIPAAm上控制释放的目的.     

Adsorption of Lead and Cadmium on Ca-Deficient Hydroxyapatite

A Ca-deficient hydroxyapatite(d-HAp) has been used to remove lead and cadmium from their mixed ions solution. The effect of pH, coexistent calcium and magnesium ions, and humic acid on the adsorption efficiency were investigated. The results showed that this d-HAp adsorbed both Cd²⁺ and Pb²⁺ efficiently within a wide pH range. The existence of humic acid reduced the removal efficiency of Cd²⁺ and Pb²⁺. The addition of Ca²⁺ and Mg²⁺ with a concentration of 500 mg/L only slightly reduced the removal efficiency. The adsorption kinetics was described by pseudo-second-order reaction model and the adsorption isotherm followed the Langmuir model.     

Functionalized silver doped hydroxyapatite scaffolds for controlled simultaneous silver ion and drug delivery

Bacterial infections are a major problem in bone tissue regeneration, thus it is essential to incorporate antibacterial properties within the bone scaffolds. Silver compounds are frequently used as antibacterial agents to prevent bacterial infections and numerous studies have shown that silver ions can be incorporated within the biocompatible and osteoconductive biomaterial hydroxyapatite (HAp) structure, but, so far, no study has thoroughly evaluated silver ion release rates in long term. Therefore, we have established a novel carrier system for local drug delivery based on functionalized silver doped hydroxyapatite with determined long term silver ion release rates. Silver ions from prepared scaffolds were released with a rate of 0.001±0.0005 wt%/h taking into account the incorporated silver amount. Moreover, lidocaine hydrochloride was incorporated in the prepared scaffolds, to provide local anesthetic effect. These scaffolds were functionalized with sodium alginate and chitosan and in vitro drug release rate in simulated body fluid was evaluated. The results suggested that the developed novel composite scaffolds possess the antibacterial activity up to one year as well as controlled anesthetic drug delivery up to two weeks.     

聚天冬氨酸衍生物的研究进展及其在药物控释和组织工程领域中的应用

聚天冬氨酸衍生物是一种具有良好生物相容性、生物降解性的新材料.作者综述了聚天冬氨酸衍生物的研究进展,介绍了共聚法、一般开环法、开环交联法制备聚天冬氨酸衍生物,以及近几年聚天冬氨酸衍生物作为共价大分子复合体、胶束药物载体、水凝胶药物载体在药物控释方面的研究进展,及其在组织工程支架上的应用.     

铁基载氧体对煤中汞释放行为的影响

采用Ontario-Hydro方法,在管式炉中考察了煤化学链燃烧/气化过程中Fe₄Al₆载氧体对煤中汞释放率、气态汞形态分布及汞在两反应器内释放行为的影响。结果表明,载氧体对煤中汞释放率具有显著的影响,在500~700℃,与无载氧体相比,化学链燃烧过程煤中汞释放率减少,化学链气化过程煤中汞释放率增大,而在900℃时,无论化学链燃烧过程还是化学链气化过程,煤中汞释放率均减小。Fe₄Al₆载氧体能够显著增加燃料反应器出口气态Hg²⁺的相对含量,其含量随温度的升高而逐渐升高。燃料反应器的温度也是影响煤中汞在两反应器中的分布以及空气反应器中不同价态汞百分含量的重要因素。此外,相同条件下不同煤种的汞释放率不同,主要与煤的组成不同有关。该研究对揭示载氧体对煤中汞迁移的影响机理以及煤化学链转化过程汞的控制提供了实验依据。     

Vancomycin loaded-mesoporous bioglass/hydroxyapatite/chitosan coatings by electrophoretic deposition

In the current research, vancomycin loaded-mesoporous bioglass/hydroxyapatite whiskers/chitosan composite coatings with drug delivery capability were fabricated on titanium substrate via electrophoretic deposition. Hydroxyapatite with whisker morphology demonstrated improvement in microhardness of the coatings. Among different initial vancomycin concentrations of 1, 5, 15, 25 and 50 mg/ml to load mesoporous bioglass particles, maximum loading efficiency and drug content (95%) were achieved at 25 mg/ml. Based on the quality of the coatings, bioglass loaded with initial concentrations of 1, 5 and 15 mg/ml drug were chosen as optimal samples for further investigations. Synergistic effect of bioglass and hydroxyapatite caused the composition with 20% and 50%Wt MBG to have faster bioactivity response. Regarding the drug delivery capability of the composite coatings, sample containing 50%Wt bioglass encapsulated with 15 mg/ml drug exhibited rapid and maximal drug release due to the facile diffusion of the solved bioglass particles. The achieved results showed the acceptable antibacterial potency of vancomycin-loaded coating to prevent infection. Moreover, existence of antibiotic did not have any toxic effect over the osteoblast cells cultured on the coatings.     

Synthesis and physical gels of pH- and thermo-responsive tertiary amine methacrylate based ABA triblock copolymers and drug release studies

A series of novel pH-responsive ABA triblock copolymer gelators have been synthesized by using poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) as the A block and poly[2-(dimethylamino)ethyl methacrylate] (PDMA) as the B block via group transfer polymerization. While the PDPA-b-PDMA-b-PDPA triblock copolymers are molecularly soluble in acidic aqueous media due to protonation of all tertiary amine groups, they formed either gels by the chain-end hydrophobic interactions with relatively high polymer concentration (10 wt%) or near monodisperse “flower” micelles with low polymer concentration at neutral and basic aqueous solutions. The hydrophobic model drug release was studied in a sustained manner from the gels at pH 7.4 by varying the polymer concentration, the polymer molecular weight and the temperature of the medium. Preliminary studies indicate that both slow, sustained release and fast, triggered release of a model hydrophobic drug, dipyridamole, can be achieved by tuning the solution pH, polymer concentration, polymer molecular weight and temperature of the gel.     

Synthesis and characterization of simple and binary drug delivery systems for sustainable release of ciprofloxacin

Biopolymers are widely used for design sustained drug delivery systems (SDDS) and biomaterials for tissue engineering. Reducing wound infections still constitutes one of the major challenges facing the wound care. The aim of this study was to synthetize, characterize and evaluate a single (polymeric spheres) and a binary polymeric biomaterial (polymeric spheres imbedded in a poly(vinyl alcohol) (PVA) scaffold) as a SDDS. Polymeric spheres were prepared by complex coacervation and the binary system of the chitosan (CH) -PVA beads embedded in a PVA scaffold prepared by Ice Segregation Induced Self-Assembly (ISISA) process. Both systems were physicochemically characterized using Fourier Transform Infrared spectroscopy (FTIR), X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). In vitro ciprofloxacin (CFX) release kinetics were evaluated simulating physiological conditions under sink conditions. Physicochemical characterization showed interactions between all components forming beads; in contrast, beads-scaffold interactions were not detected making evident the presence of two different phases in the binary system. The CFX release kinetics revealed that both systems were SDDS, simple system release 97.0?±?6.9% in 7 days, while the binary was 68.56?±?6.6% during 14 days of evaluation. Binary system emerges as a potential tool for evaluate the long-lasting infection control in the treatment of skin wounds.     

Relations between apparent and intrinsic kinetics of “programmable” drug release in human plasma

To better understand and “program” the drug release in human plasma, a kinetic characterization of the process is necessary for every drug ligand and macromolecular support. Due to few observed species and limited standard information, process modelling based on extended kinetic structures is difficult. Laboratory experiments that mimic the natural conditions and the bio-environment, together with statistical estimators allow identification of reduced (apparent) kinetic models. The scope of this paper is to present a more systematic approach to interpret the kinetic models and to link the identified apparent rate/equilibrium constants to kinetic characteristics of an extended “intrinsic” reaction path. The developed stoichiometric analysis and linear lumping rules are exemplified for a case study from literature, that considers a four-ligands (“drug” dansyl groups) release from a dendrimeric support structure in a reducing environment that mimic the human plasma.     

Extraction of chitosan from Aspergillus niger mycelium and synthesis of hydrogels for controlled release of betahistine

Chitosan was extracted from the fungus Aspergillus niger, an alternative source of chitin that is widely available as a byproduct of the industrial production of citric acid. Chitosan with deacetylation degree (DD) of 73.6% was characterized by elemental analysis, capillary viscometry (molecular weight of 1.9 × 10⁵ g/mol), Fourier transform infrared (FTIR), nuclear magnetic resonance (¹H NMR, ¹³C NMR and ¹⁵N NMR) spectroscopies, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Fungal chitosan was crosslinked with glutaraldehyde and glutaric acid to obtain hydrogels. Chitosan hydrogels were characterized by FTIR and by scanning electron microscopy (SEM), which showed that these materials have irregular, polydisperse, and interconnected pores. Kinetic studies of the release of betahistine from the swollen hydrogels showed a Fickian diffusion mechanism. Finally, hydrolytic degradation of chitosan hydrogels under simulated physiological conditions (pH 7.4 and 37 °C) was investigated as well as in vivo biocompatibility tests using New Zealand white rabbits as animal models.     

Effect of the intercalation agent content of montmorillonite on the swelling behavior and drug release behavior of nanocomposite hydrogels

A series of novel dual functional nanocomposite hydrogels were prepared from N‐isopropylacrylamide (NIPAAm), acrylic acid (AA) that is neutralized 50 mol % by sodium hydroxide (SA50), and montmorillonite (MMT). MMT was intercalated with three different contents of intercalation agent of (3‐acrylamidopropyl) trimethyl ammonium chloride (TMAACl). Investigation of the effect of intercalated MMT with three contents of intercalation agent (TMAACl) in the present nanocomposite hydrogels on the swelling and drug release behaviors is the main purpose in this study. The microstructure was identified by X‐ray diffraction (XRD). Results showed that the swelling ratio for the present nanocomposite hydrogels decreased with an increase in the content of the intercalation agent. The gel strength of the present gels did not change obviously with an increase in the content of intercalation agent. XRD results indicated that exfoliation of MMT was achieved in the dry and swollen gel state. Finally, the drug release behaviors for these gels were accessed also. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 74–82, 2004     

Synthesis of mesoporous CuFe2O4@SiO2 core-shell nanocomposite for simultaneous drug release and hyperthermia applications

In the present work, magnetic CuFe₂O₄ nanoparticles were synthesized through a sol-gel combustion. The synthesized CuFe₂O₄ were coated with mesoporous SiO₂. The synthesized CuFe₂O₄@SiO₂ nanocomposite was investigated for drug release and hyperthermia applications. The products were studied by X-ray diffraction analysis, Fourier-transform infrared spectroscopy, simultaneous thermal analysis, Brunauer-Emmett-Teller surface area, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometer. TEM images showed the formation of silica coating with a thickness of 14 nm around copper ferrite. The surface area of the samples increases from 2.59 to 199.2 m²/g after the surface modification of ferrites nanoparticles with silica. The CuFe₂O₄@SiO₂ exhibited high ibuprofen loading and controlled drug release. These improvements resulted from the nanocomposite's mesoporous structure and high surface area. Coating CuFe₂O₄ nanoparticles with mesoporous silica reduced the cytotoxicity and improved drug release properties. However, this coating reduced the hyperthermia ability. The formed CuFe₂O₄@SiO₂ nanocomposites show high potential for simultaneous drug release and hyperthermia applications with prospective use for biomedical applications.     

Hierarchical self-assembled hollow hydroxyapatite flower microspheres containing terpene functional groups for efficient drug loading and pH-responsive drug release

In this paper, we fabricated hierarchical self-assembled hollow rose-like flower microspheres (HRFM) and hollow burr-like flower microspheres (HBFM) hydroxyapatite (HAP) using dehydroabietyl phosphate tri-ester (DDPT) as an organic phosphorus source, a regulating agent, and a soft template simultaneously via a one-step solvothermal method. The HBFM and HRFM have been explored for their application in drug delivery, using doxorubicin (DOX) as a drug model. The formation mechanisms of HRFM and HBFM were proposed on the basis of the electrostatic potential diagrams and self-assembled behavior of DDPT organic molecule. After the rosin-based terpene functional groups were incorporated, both HRFM and HBFM exhibited low cytotoxicity against Hela cell, pH-dependent sustained drug release properties, and high drug loading capacity. The drug-loading capacities of HBFM and HRFM were 116.6?mg?g^?1 and 148.3?mg?g^?1, respectively. Thus, the as-prepared HRFM and HBFM are promising for the applications in drug delivery.     

Effect of fluorinated hydrophobic monomer on the drug release behavior for the thermosensitive hydrogels

Three series of copolymeric gels based on N‐isopropylacrylamide (NIPAAm) and perfluoroalkyl methacrylate such as 2,2,3,3,4,4,5,5‐octafluoropentyl methacrylate (OFPMA), 4,4,5,5,6,7,7,7‐octafluoro‐2‐hydroxy‐6‐(trifluoromethyl)heptyl methacrylate (OFHHMA), and 3,3,4,4,5,6,6,6‐octafluoro‐5‐(trifluoromethyl)hexyl methacrylate (OFHMA), were prepared by emulsion polymerization. The effect of perfluoroalkyl methacrylate and sodium lauryl sulfate (SLS), which can act as a surfactant and a pore‐forming agent, on the equilibrium swelling ratio and mechanical properties of the present hydrogels was investigated. Results show that hydrophobic monomers made the swelling ratio of the gel decrease and the mechanical property of the gel increase; however, SLS exhibits a contrary result. In addition, the effect of perfluoroalkyl methacrylate on the drug release behavior was also investigated. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4661–4667, 2006     

An examination of the thermorheological and drug release properties of zinc tetraphenylporphyrin-containing thermoresponsive hydrogels, designed as light activated antimicrobial implants

This study describes the thermorheological, mechanical and drug release properties of novel, light-activated antimicrobial implants. Hydrogels, based on N-isopropylacrylamide (NIPAA) and hydroxyethylmethacrylate (HEMA) and either devoid of or containing zinc tetraphenylporphyrin, were prepared by free radical polymerisation and characterised using oscillatory rheometry and texture profile analysis. Drug release was studied at both 20 and 37 °C. Hydrogels containing NIPAA exhibited a sol-gel temperature (Tm), which increased as the proportion of HEMA increased and was . The viscoelastic properties (storage modulus G^′, loss modulus G^″, loss tangent and dynamic viscosity η^′) were affected by hydrogel composition and temperature, with the copolymers exhibiting lower values of G^′,G^″ and η^′ values than either homopolymer. Similar relationships between the composition of the hydrogels and the textural/mechanical properties were observed. At 37 °C rheological structuring (increased G^″,G^″,η^′ and reduced loss tangent) occurred for all NIPAA-containing polymers and increased as the NIPAA content increased. At 20 °C drug release was diffusion controlled, the rate of which was similar for all NIPAA-containing polymers and was lower than drug release from p(HEMA), despite the greater elasticity of this homopolymer. At 37 °C drug release from the NIPAA-containing hydrogels was initially non-diffusion controlled, following which drug release levelled. Drug release decreased as the NIPAA content increased and correlated to hydrogel elasticity. It is suggested that the ability to engineer the release of Zn-TPP from these hydrogels, in conjunction with their acceptable mechanical properties, may be clinically advantageous for the treatment of infection.     

The effect of buffer concentration,pH and buffer ions on the degradation and drug release from polyglycolide

Samples of polyglycolide were degraded in various buffered solutions in order to investigate the effects of buffer concentration, pH and particular buffer ions on the hydrolysis reaction. The small‐angle X‐ray scattering profiles changed with degradation; long periods were calculated and their changes with degradation used as a measure of the degradation rate. The release of a model drug, theophylline, was also investigated under these different buffering conditions. In more concentrated buffer solutions theophylline was released slightly earlier and the samples began to swell sooner. Increasing the pH of the phosphate buffer also resulted in an earlier swelling and release of drug. These effects were attributed to the neutralisation and increased solubility of acidic degradation products in more concentrated or alkaline buffer solutions. When an imidazole–HCl rather than a phosphate or citrate–citric acid buffer system was used, swelling and drug release were accelerated, as imidazole catalysed the ester hydrolysis reaction. The results are interpreted within the context of a four‐stage model of PGA degradation. © 2003 Society of Chemical Industry     

Manipulating drug release from tridimensional porous substrates coated by initiated chemical vapor deposition

In the recent years, modern wound dressings have attracted much interest to accelerate wound healing processes with the topical delivery of drugs directly on wounds having a significant effect on wound rehabilitation. The objective of this study was to develop a model dressing that would not only provide wound protection from the environment but might also provide the possibility to keep it moist and deliver a drug for potential speeding the healing process. Poly(ethylene terephthalate), cotton fabrics, and polycaprolactone (PCL) nanofibers were used as different tridimensional porous substrates, loaded with a model drug, clotrimazole. The results show that the chemical structure and surface area to volume ratio of the pristine substrates affect the drug release profile. Coating of such substrates by hydrogels poly(2-hydroxyethyl methacrylate) (p-HEMA) and poly(methacrylic acid) (p-MAA) was successfully achieved by initiated chemical vapor deposition. This method was chosen because it is gentle and solventless and most important it can coat free areas within the three-dimensional structures. Scanning electron microscopy results revealed that p-HEMA and p-MAA conformally coated the fibers of the substrates. Moreover, drug release experiments showed that p-HEMA and p-MAA coatings provide barriers preventing sudden drug release. In conclusion, our results indicated the possibility of fabricating dressings containing a drug with tunable drug release profile depending on several parameters even though a strong porous structure exists. © 2019 The Authors. Journal of Applied Polymer Science published by Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47858.