Electrosprayed tricalcium phosphate spherical microcups and antibiotic drug delivery

Here we prepared tricalcium phosphate (TCP) spherical cups of a few micrometers in size (average = 2.74 μm) by applying the electrospraying method. The sol-gel precursor containing calcium and phosphate (Ca/P = 1.5) was mixed with Polyvinylpyrrolidone in ethanol at varying concentrations, and then sprayed under a controlled electrostatic field. The jets from the sol-gel solution changed from a complete fibrous mesh into a formation of microbeads connected with fibers and then further into a complete formation of microbeads as the solution viscosity became decreased. After the thermal treatment (800-1100 °C), individual microbeads remained, to form the shape of a spherical cup and retained the phase of β-TCP. The drug delivery potential of the TCP micro-cups, as assessed by using an antibiotic drug ampicillin, demonstrated a dose dependent loading capacity and almost a linear release profile over a day.     

Calcium pectinate capsules for colon-specific drug delivery

The calcium pectinate (CaP) capsule, a novel, colon-specific delivery system, was designed and developed using 5-fluorouracil (5-FU) as a model drug. Technically, CaP capsules were prepared by dipping a glass or stainless steel rod successively into pectin and calcium chloride solutions, followed by subsequent air-drying and coating. In vitro studies showed that the release of 5-FU from CaP capsules markedly increased in the presence of rat cecal contents, and the release characteristic was mainly associated with some capsule parameters such as calcium content, shell thickness, and coat amount. Gamma scintigraphic studies demonstrated that CaP capsules could pass through the stomach and small intestine intact and could release drug in colon. The 5-FU releasing characteristics acquired both from in vitro biomimic dissolution experiments and from healthy volunteers indicated that the newly developed CaP capsule possessed the ideal colon-specific drug delivery characteristic.     

Preparation and properties of phosphogypsum/amino acid copolymer porous composite for medical application

用化学共沉淀法合成了钙磷原子比（Ca/P）为1.50和1.67的磷石膏（PG）,用熔融聚合法制备四元氨基酸共聚物（PAA4）,用挤出发泡法制备了两种磷石膏/四元氨基酸共聚物（PG/PAA4）多孔复合材料。通过TGA、SEM、XRD、IR、EDS等对两种复合材料的组成结构进行了表征,并研究了复合材料在磷酸缓冲液（PBS）中的体外降解性能。结果表明：无机组分PG在两种复合材料中分布均一,质量分数均为60%左右;PG/PAA4复合材料的孔径为100～400μm,孔隙率在60%左右;多孔复合材料的有机和无机相之间有化学作用。PG/PAA4复合材料具有良好的体外降解性能,其失重率随PG钙磷比的增加而增加,降解液的pH值维持在6.9～7.4之间。PG/PAA4复合材料降解后,其表面沉积了片状钙磷化合物,推测该复合材料可能具有生物活性。     

聚乳酸嵌段共聚物的制备及扩链研究

为了获得性能更优良的聚乳酸材料,以乳酸、ε-己内酯、丁二酸酐为原料,采用梯度升温法合成了聚乳酸嵌段共聚物,用IPDI对其扩链.采用乌氏黏度法、FT-IR、1H-NMR、TGA及XRD等手段对产物进行了表征.FT-IR和1H-NMR测试结果显示,预期的聚乳酸嵌段共聚物成功合成;几种聚合方法中,以先合成端羟基活性低聚物P(...     

Ultra-small MoS_2 nanodots-incorporated mesoporous silica nanospheres for pH-sensitive drug delivery and CT imaging

Functionalization of mesoporous silica spheres with well-dispersed and ultra-small nanodots to exert their synergistic effects for biomedical applications has been considered to be an urgent challenge.Herein,homogeneously incorporation of ultra-small and monodispersed MoS₂ nanodots in the mesoporous silica nanospheres(MSN)was achieved by a facile one-step solvothermal reaction.The as-synthesized UsMSND@MSN possessed uniform size(~115 nm)and favorable biocompatibility inherited from MSN.The dispersed UsMSND within MSN could act as anchoring sites for aromatic anti-cancer drug DOX loading,and consequently achieved pH-responsive release based on the specialπ-π/electrostatic interactions with the DOX molecules.More importantly,the well-dispersed UsMSND in MSN could function as the non-toxic contrast agent for the sensitive in vivo CT imaging in various tumors including breast cancer and glioma with different sections.This work promises a good strategy for dispersed incorporation of UsMSND into MSN as an excellent pH-responsive platform for simultaneous cancer imaging and therapy.     

智能药物释放材料的合成与应用

本文阐述了智能药物释放材料的控制释放机理,并介绍了近年来智能药物释放材料合 成与应用的最新进展。     

Synthesis of heteropoly oxometalate/amphiphilic block copolymer composite thin films with self-ordered mesostructures

A simple, reproducible, and versatile procedure for synthesizing mesostructured 12-phosphotungstic acid thin films with large spaced mesostructures (< 17 nm) using amphiphilic block copolymers as structure-directing agents is reported. The morphology of the mesostructure can be controlled by adjusting the m/n ratio of poly (ethylene oxide)_1/2/poly (propylene oxide) (EO_1/2/PO) in the tri-block copolymer (EO)_m(PO)_n(EO)_m. This synthetic approach was adapted to prepare mesoscopically ordered heteropoly oxometalates (HPOMs) films, including 12-phosphomolybdic acid and 12-tungsto (IV) silicic acid. The electrochemical properties of the calcined HPOMs films as electrodes in Li-ion batteries were also investigated.     

Alginate in drug delivery systems

Alginates are established among the most versatile biopolymers, used in a wide range of applications. The conventional use of alginate as an excipient in drug products generally depends on the thickening, gel-forming, and stabilizing properties. A need for prolonged and better control of drug administration has increased the demand for tailor-made polymers. Hydrocolloids like alginate can play a significant role in the design of a controlled-release product. At low pH hydration of alginic acid leads to the formation of a high-viscosity “acid gel.” Alginate is also easily gelled in the presence of a divalent cation as the calcium ion. Dried sodium alginate beads reswell, creating a diffusion barrier decreasing the migration of small molecules (e.g., drugs). The ability of alginate to form two types of gel dependent on pH, i.e., an acid gel and an ionotropic gel, gives the polymer unique properties compared to neutral macromolecules. The molecule can be tailor-made for a number of applications. So far more than 200 different alginate grades and a number of alginate salts are manufactured. The potential use of the various qualities as pharmaceutical excipients has not been evaluated fully, but alginate is likely to make an important contribution in the development of polymeric delivery systems. This natural polymer is adopted by Ph.Eur. It can be obtained in an ultrapure form suitable for implants. This review discusses the present use and future possibilities of alginate as a tool in drug formulation.     

用于肺部给药的壳聚糖空心微球的制备

采用壳聚糖为壁材、烷基多糖苷为赋形剂通过喷雾干燥的方法成功制备出了可用于肺部给药的空心载药微球,其粒径在10μm左右。采用扫描电子纤维镜观察了所得粒子的形貌,并分析了喷雾干燥条件下得到这种薄壁空心结构的原理。     

Synthesis and characterization of three-arm polyamide 6-polyurethane block copolymer by monomer casting process

Three-arm polyamide 6-polyurethane (PA 6-PU) block copolymers were synthesized using ε-caprolactam as a monomer, caprolactam sodium as a catalyst, and a three-arm carbamyl caprolactam terminated polyurethane (PU) prepolymer as macroactivator. The three-arm PU prepolymer was formed from polyether glycerol (PPG) and diphenyl methane-4,4′ diisocyanate (MDI). The block copolymers were obtained using the monomer casting process (MC) of ε-caprolactam at different content of three-arm PU prepolymer (5–20%). In increasing the content of the soft phase, in Fourier transform infrared (FTIR), a displacement was observed in the band at 1637 cm⁻¹, which is assigned to the amide I of polyamide 6 (PA 6) shifted to a higher wavenumber. This suggested an interaction between the amide group of the PA 6 and the urethane group of the PU. The effects of the PU prepolymer content on the mechanical properties of the block copolymers were investigated. The results showed that the impact strength of the block copolymers at 25 °C and −50 °C temperature could be significantly improved. The crystallization and melting behaviors, structure and thermal properties and morphological characteristic of the block copolymers were studied using the different techniques such as differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMTA) and scanning electronic microscopy (SEM).     

多孔球形羟基磷灰石的制备及其药物控释性能的研究

研究了多孔球形羟基磷灰石生物材料的制备及其对药物的控释性能。采用微乳液法先制得多孔球形碳酸钙,并以此为模板与磷酸氢二钠在一定条件下反应制备出多孔球形羟基磷灰石,通过X射线衍射,扫描电子显微镜等手段对制备的羟基磷灰石的组成和形貌进行了表征,并以硫酸庆大霉素为模型药物,研究了多孔球形羟基磷灰石对庆大霉素的体外释放规律。结果表明制备的多孔球形羟基磷灰石直径约10μm,粒度均匀,分散良好,且对庆大霉素的载药率为18.0%,包封率为46.0%,持续释药时间达到10d。多孔球形羟基磷灰石作为药物载体材料对药物具有很好的缓释作用。     

Dendron-polymer hybrid mediated anticancer drug delivery for suppression of mammary cancer

Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity.Here we report a dendronized polymer-doxorubicin(DOX)hybrid(DPDH)with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate(LPDC).The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4.DPDH efficiently enters 4 T1 cells and releases DOX to induce cytotoxicity and apoptosis.Owing to the dendronzied structure,DPDH has a significantly longer blood circulation time than LPDC.DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4 T1 mammary cancer model than LPDC as well as free drug,evidenced from tumor growth inhibition,TUNEL assessment and histological analysis.Biosafety of DPDH is also confirmed from hemolysis,body weight shifts during treatment and pathological analysis.This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.     

Role of macropore size in the mechanical properties and in vitro degradation of porous calcium phosphate cements

The goal of the present study was to investigate the effect of macropore size on the compressive strength and in vitro degradation of porous calcium phosphate cements (CPCs). For this purpose, a series of porous CPCs with three different macropore sizes (200-300 μm, 300-450 μm and 450-600 μm) and comparable porosity were prepared by salting-out method, and the study of in vitro degradation behavior was carried out under a constant fluid flow environment. The results showed that the increase in macropore size of CPCs with invariant porosity resulted in a decrease in the compressive strength but an increase in the degradation rate of CPCs significantly, suggesting the possibility that the degradation rate and compressive strength of biomaterials can be regulated by varying the macropore size while maintaining the porosity unchanged.     

含锶磷酸钙骨水泥的制备及性能研究

通过混合磷酸四钙、磷酸氢钙、磷酸氢锶及稀磷酸制备了一种含锶磷酸钙骨水泥(Sr-CPC),研究了水泥固/液比、含锶量及仿生浸泡时间对其结构组态及抗压强度的影响.结果表明,不同组分的CPC在调和浆体时均存在最佳固/液比,且对应的凝结时间适合临床手术要求;Sr-CPC试样在模拟体液(SBF)中浸泡24h后固化产物为含锶缺钙羟基磷灰石;适量锶的加入及较短时间仿生浸泡均可显著改善Sr-CPC固化体的抗压强度,并且浸泡过程对固化体抗压强度的影响主要体现在其微观结构的变化.     

Preparation of alginate microspheres by water-in-oil emulsion method for drug delivery: Effect of Ca2+ post-cross-linking

Alginate microspheres were prepared by a water-in-oil emulsion solvent diffusion method. The alginate microspheres were post-cross-linked with Ca²⁺ ions. Influence of Ca²⁺ concentration on the characteristics and drug release behaviors of alginate microspheres was evaluated. Blue dextran was used as a water-soluble model drug. The non-cross-linked alginate microspheres were less than 100 μm in size and had a spherical shape. The cross-linked alginate microspheres were also spherical in shape with a rougher surface but their particle sizes were larger than 100 μm. The drug encapsulation efficiency of the non-cross-linked alginate microspheres was very high (82%). The drug encapsulation efficiency of alginate microspheres cross-linked with 5% and 10% Ca²⁺ concentrations were similar to the non-cross-linked microspheres. The in vitro drug releases of the cross-linked alginate microspheres showed prolong release profiles. The cumulative release of blue dextran decreased as the Ca²⁺ concentration increased. Thus, Ca²⁺-post-cross-linked alginate microspheres show possibility for use as controlled-release drug carriers.     

新型分离-吸附腈氯纶纤维的制备及其应用研究

利用自制的含活性炭的腈氯纶纤维制备了羧酸型离子交换吸附纤维,研究了所制得的含活性炭的腈氯纶离子交换吸附纤维的性能,尤其是对L-精氨酸的吸附性能,考察了其静态、动态吸附情况.结果表明,静态饱和吸附量随精氨酸起始浓度的增加而增加,吸附率随精氨酸起始浓度的增加而降低,且遵循Freundlish等温吸附模式.所制得的纤维对精氨酸的动态吸附能力较强,吸附和解吸速率较快.     

Superparamagnetic magnesium ferrite/silica core-shell nanospheres: A controllable SiO2 coating process for potential magnetic hyperthermia application

The control of coating shell becoming important to improve the applicability of magnetic nanoparticles. Herein, we present the scalable technique for preparing MgFe₂O₄/SiO₂ core-shell nanospheres with finely tuned shell thickness and their efficiency in magnetic hyperthermia heating agent. At first, MgFe₂O₄ dense nanosphere derived from one-step ultrasonic spray pyrolysis (USP) technique. Silica shells were then coated on the as prepared nanospheres with tunable thickness from 10 to 30 nm. We show that the thickness of this coating is finely controlled at allowing our proposed level by using the required amount of SiO₂ precursor (SiC₈H₂₀O₄)/acidic catalyst (HCl) ratio where the surface area of core nanospheres are significantly considered. X-ray diffraction reveals the cubic spinel ferrite structure of core particles with crystallite size 9.6 ± 1.8 nm and Fourier transform infrared spectrum analysis confirmed the formation of SiO₂. The morphological observation clarified the uniform and smooth SiO₂ shell where core-shell nanostructure is highly monodispersed in a liquid medium. M-H loops confirmed the superparamagnetic nature of all samples at room temperature. Significantly reduced ion release concentration in an aqueous solvent of the coated nanospheres compared with uncoated sample demonstrates the hermetically coating feature of dense SiO₂. This MgFe₂O₄/SiO₂ core-shell nanospheres with thine SiO₂ shell (10 nm) shows effective heating rate in the operative region (<46 °C) which makes them promising candidates for application as magnetic hyperthermia heating agent.     

Preparation and Characterization of Porous Calcium Phosphate Bioceramics

β-tricalcium phosphate (β-TCP) powder and Na2O-CaO-MgO-P2O5 glass binder were synthesized and mixed, and then the biodegradable porous calcium phosphate ceramics were successfully prepared by foaming and sintering at 8500C. The as-prepared ceramics possess a high porosity with partial three-dimension intercon- nected macro- and micro-pores. As in vitro experiment testified, the calcium phosphate ceramics (CPCs) has good degradability.     

Microneedles for transdermal drug delivery: a systematic review

Transdermal route has been explored for various agents due to its advantage of bypassing the first pass effect and sustained release of drug. Due to strong barrier properties of the skin, mainly stratum corneum (SC), the delivery of many therapeutic agents across the skin has become challenging. Few drugs with specific physicochemical properties (molecular weight <500?Da, adequate lipophilicity, and low melting point) can be effectively administered via transdermal route. However, delivery of hydrophilic drugs and macromolecular agents including peptides, DNA and small interfering RNA is challenging. Drug penetration through the SC may involve bypass or reversible disruption of SC layer by various means. Recently, the use of micron-scale needles has been proposed in increasing skin permeability and shown to dramatically increase permeation, especially for macromolecules. Microneedles (MNs) can penetrate through the SC layer of the skin into the viable epidermis, avoiding contact with nerve fibers and blood vessels that reside primarily in the dermal layer. This review summarizes the types of MNs and fabrication techniques of different types of MNs. The safety aspects of the materials used for fabrication have been discussed in detail. Biological applications and relevant phase III clinical trials are also highlighted.