HA/GCPU复合多孔支架的可控制备及细胞相容性

以脂肪族异佛尔酮二异氰酸酯(IPDI)作为硬段、蓖麻油甘油酯(GCO)作为软段,通过原位聚合法制备了羟基磷灰石/蓖麻油甘油酯基聚氨酯(HA/GCPU)复合多孔支架.利用红外光谱和扫描电子显微镜对复合支架进行表征,并测试其力学性能及孔隙率.研究结果表明,HA/GCPU复合多孔支架的孔隙率和抗压强度依赖羟基磷灰石的含量,并具有明显的可控性.HA质量分数分别为0,20%和40%时,HA/GCPU复合多孔支架孔隙率分别为(61±3)%,(68±2)%和(57±3)%,抗压强度分别为(605±61),(2125±58)和(4588±260)k Pa,可见HA质量分数为20%时,HA/GCPU复合多孔支架具有与松质骨较为匹配的孔隙率和抗压强度.将MG63细胞与多孔支架共培养,通过倒置显微镜和扫描电子显微镜观察,用噻唑蓝(MTT)法表征HA/GCPU复合多孔支架的细胞相容性,结果表明,HA/GCPU复合多孔支架表面细胞黏附,生长良好,无细胞毒性,在骨组织工程领域具有一定的应用前景.     

循环应力下PLGA多孔支架对地塞米松的控制释放

摘要 采用喷雾干燥法制备包载地塞米松(Dex)的聚L-丙交酯-b-聚乙二醇(PLLA-PEG)微球, 以热致相分离/粒子洗去法制备聚乙交酯-co-丙交酯(PLGA)多孔支架, 通过复合溶结法将载药微球固定于PLGA多孔支架中, 制得载药微球-支架(记为MS-S). 另外, 在支架制备过程中将Dex直接加入PLGA溶液中, 制得对比的直接载药支架(记为D-S). 以扫描电镜观察微球和支架的微观形貌, 在循环压应力与水浴摇床两种环境下分别对上述两种载药支架进行控制释放Dex的实验, 用紫外-可见光分光光度计测定Dex的累积释放量. 结果表明, Dex及微球的载入对PLGA支架的整体形貌影响较小; 循环压应力显著提高了Dex从载药支架中的释放速率, 与D-S相比, MS-S延缓了药物的释放. 研究模拟体内循环压应力下支架控制释放药物规律对于实现理想的临床效果具有重要意义.     

纳米孔硅灰石载药抗菌止血材料的研究

采用溶胶-凝胶法,以聚氧乙烯-聚氧丙烯-聚氧乙烯三嵌段共聚物(P₁₂₃)为模板剂,合成了纳米孔硅灰石(np-WT),用np-WT载盐酸万古霉素研制了一种新型的载药抗菌止血材料,并对其止血性能进行了研究。结果表明：np-WT具有排列有序的纳米孔道结构,其孔径在2 nm左右,高比表面积的np-WT能够明显地缩短体外部分凝血活酶时间(APTT)和凝血酶原时间(PT)。载药np-WT能够在磷酸缓冲溶液(PBS)中缓慢地释放药物,载药np-WT对其凝血性能没有明显的影响。载药np-WT对大肠杆菌有很好的抗菌作用,细胞毒性实验表明：载药np-WT无细胞毒性。载药np-WT具有很好的止血性能,能够阻止兔背部伤口的流血和缩短其流血时间。     

三维打印双固化POXC/CPC可降解骨修复支架

从成分设计和结构控制着手,在木糖醇部分取代1,8-辛二醇与柠檬酸聚合反应制备聚(柠檬酸-辛二醇-木糖醇)酯(POXC)的基础上,采用POXC预聚体与磷酸钙骨水泥(CPC)悬浮体三维打印了孔道贯通的POXC/CPC多孔复合预支架,并进一步采用固化反应制备得到该复合支架。探索了材料的可打印参数,评价了复合支架的降解性、润湿性以及生物相容性。结果表明,POXC的降解速率随着木糖醇取代度的增加而增大。56d后,POXC/CPC降解率高达43%,对照组聚(1,8-辛二醇-柠檬酸)酯/CPC(POC/CPC)降解率近10%,这是由于POXC与复合支架的贯通孔结构的协同作用所致。木糖醇的引入及其与CPC的复合大大提高了支架的亲水性,有利于细胞的黏附和增殖。POXC/CPC支架具有贯通的大孔结构、良好的生物相容性和降解性,可促进骨缺损的修复。     

非化学计量羟基磷灰石骨水泥的制备及性能研究

采用磷酸四钙和磷酸氢钙混合粉末制备了nCa/nP比为1.58的非化学计量羟基磷灰石骨水泥(n-HAC)及其多孔支架材料。结果表明:与nCa/nP=1.67的化学计量羟基磷灰石骨水泥(HAC)相比,n-HAC的凝结时间和抗压强度没有明显的区别。XRD和IR显示:n-HAC与HAC都为羟基磷灰石结构,但n-HAC在Tris-HCl缓冲溶液的降解性明显大于HAC。细胞培养结果表明:成骨细胞在n-HAC和HAC两种材料上的粘附和细胞形态没有明显的区别,但细胞在n-HAC上的增殖率明显高于HAC。将多孔n-HAC支架材料植入兔股骨缺损处,观察其修复骨缺损情况,组织学分析结果表明:新生骨在多孔支架的表面形成,并长入其内部;n-HAC在体内的降解比HAC快,能明显地促进新骨生成。     

多孔羟基磷灰石纳米球作为抗坏血酸载体的研究

利用超声辅助的化学共沉淀法制备了羟基磷灰石纳米材料, 并实现了其对抗坏血酸的包载. 采用透射电镜、氮气吸附孔径分析仪、X射线粉末衍射仪、傅里叶红外光谱仪和紫外分光光度计等对所得纳米材料的微观形貌、孔径分布、物相、表面官能团和负载抗坏血酸量进行了表征和分析, 并在超声辅助条件下进行了药物释放动力学研究. 结果表明, 在抗坏血酸存在的条件下, 利用声化学方法可以制得多孔的羟基磷灰石纳米球, 其平均直径约为140 nm, 平均孔直径约为15 nm, 可实现对抗坏血酸的包载. 此外, 在超声辅助的条件下, 该纳米球具有持续释药的能力, 不同的超声功率能改变载药粒的释药速度, 表明这种多孔羟基磷灰石纳米球是一种具有很大应用前景的骨组织药物载体.     

肾上腺髓质素微球复合PLGA/纳米羟基磷灰石支架材料的制备及生物活性评价

利用离子乳化交联法制备了负载肾上腺髓质素的壳聚糖微球,应用热致相分离法制备了乳酸和乙醇酸共聚物/纳米羟基磷灰石(PLGA/nHA)支架材料并在其中包覆载药微球.通过扫描电子显微镜、体外释放行为、材料溶血行为、碱性磷酸酶(ALP)活性的测定、支架材料表面细胞荧光染色和MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐]比色法等手段综合评价载药支架材料的性能及生物活性.结果表明,微球直径均匀,载药支架孔径大小合适并相互穿通.支架材料的溶血率小于5%,符合医用材料的溶血实验要求.载药支架及支架材料本身对成骨细胞及血管内皮细胞的增殖以及成骨细胞的分化均有一定的促进作用.     

微乳液法制备可共载水溶和脂溶药物的壳聚糖季铵盐乙醇脂质体的载药性能表征

采用微乳液法制备了可包载脂溶性和水溶性药物的羧甲基壳聚糖十八烷基季铵盐(OQCMC)乙醇脂质体,研究了OQCMC乙醇高分子脂质体的相图、粒径和电位、对药物的包封及释放能力及共载水溶性和脂溶性荧光染料后的细胞内递送能力.结果表明:OQCMC上长链季铵盐分子的取代度和共乳化剂乙醇的加入量对相图中微乳区域的面积影响不大;微乳液法可制备包载水溶性长春新碱(VCR)、脂溶性消炎痛(IMC)或二者共载的OQCMC载药微球,微球粒径为(52.40±0.55)nm,分布均匀;微乳液体系对VCR的最大载药率为22.7%,对IMC的最大载药率为20.1%,二者共载时,VCR的最大载药率为12.2%,IMC的最大载药率为10.0%;载药微球对药物具有缓控释功能.OQCMC乙醇高聚物脂质体可有效地包载荧光染料异硫氰酸荧光素FITC(水溶性)和尼罗红(脂溶性),并将二者递送到卵巢癌HO8901细胞内.     

镁掺杂纳米羟基磷灰石的制备及其在载药方面的应用

通过逐步沉淀反应一锅法制备了一系列不同含量的镁掺杂纳米羟基磷灰石。通过硝酸镁、硝酸钙不同的投料物质的量比调控纳米颗粒的形态和尺寸。通过透射电子显微镜(TEM)、X射线衍射(XRD)等分析手段对镁掺杂纳米羟基磷灰石进行物理化学性能表征,用MTT法评价其体外细胞毒性。研究结果表明:镁掺杂纳米羟基磷灰石呈现束状纳米纤维形态、比表面积大、细胞毒性较低;将其作为载体负载抗癌药物顺铂,具有很好的载药能力,载药量可达54%,该载药纳米颗粒还具备缓释特性(72 h释药量达到41.72%)和很好抑制癌细胞生长的效果。     

环状RGDs修饰的分子刷型共聚物在成像及药物运输中的应用

以具有丰富接枝侧链的阴离子型共轭聚合物分子刷PFPANa为材料,通过简单的一步修饰法在聚合物的部分接枝侧链上引入靶向配体分子c(RGDyK),并利用分子刷侧链上未修饰配体分子的羧基负离子与抗癌药物DOX静电结合,制备了基于分子刷型共轭聚合物的靶向细胞成像和载药系统.研究结果表明载药系统对DOX药物的载药量可达13.3 wt%,体外细胞实验研究结果表明该载药系统可实现对肿瘤细胞的靶向选择性成像,并显著促进了肿瘤细胞对DOX药物的摄取,具有良好的抗肿瘤细胞生长效果,显著提高了药物运输效率.     

Enhanced Anticancer Efficacy by ATP‐Mediated Liposomal Drug Delivery

A liposome‐based co‐delivery system composed of a fusogenic liposome encapsulating ATP‐responsive elements with chemotherapeutics and a liposome containing ATP was developed for ATP‐mediated drug release triggered by liposomal fusion. The fusogenic liposome had a protein–DNA complex core containing an ATP‐responsive DNA scaffold with doxorubicin (DOX) and could release DOX through a conformational change from the duplex to the aptamer/ATP complex in the presence of ATP. A cell‐penetrating peptide‐modified fusogenic liposomal membrane was coated on the core, which had an acid‐triggered fusogenic potential with the ATP‐loaded liposomes or endosomes/lysosomes. Directly delivering extrinsic liposomal ATP promoted the drug release from the fusogenic liposome in the acidic intracellular compartments upon a pH‐sensitive membrane fusion and anticancer efficacy was enhanced both in vitro and in vivo.     

可降解自固化类骨磷灰石支架的研究

0引言一直以来,钙磷生物材料如羟基磷灰石(hy-droxyapatite,HA)由于其成份与骨的无机成份相似,具有良好的生物相容性,作为骨修复材料引起了人们广泛的兴趣。磷酸钙骨水泥是一类可在生理条件下自固化的非陶瓷型类HA人工骨材料,这种由磷酸钙骨水泥(calcium phosphate cement,CPC)转变而成的HA,与天然骨磷灰石有类似的组成结构,植入人体后可参与新陈代谢,促进骨组织生长[1,2]。一些研究显示,CPC具有成骨活性和生物降解性,在体内被吸收的同时可引导新骨的生成,从而可克服自体骨、磷酸三钙陶瓷因吸收降解过快造成的局部缺陷以及陶瓷型HA长…     

Bone cell activity responsive drug release from biodegradable apatite/collagen nano-composite cements--in vitro dissolution medium responsive vitamin K2 release

A biodegradable drug delivery system with perforated macro pores was established using an apatite/collagen composite cement containing menatetrenone (VK2). The drug-release capabilities of the device were investigated in vitro under osteoblast and osteoclast-like conditions (SOB and SOC). A bulk powder of apatite cement containing 2.5% VK2 and 20% bovine collagen was obtained by grinding, kneaded with phosphoric acid, and poured into molds, producing fixed blocks with 0-60 perforated macro pores. The characteristics of these samples were measured by X-ray powder diffraction analysis and Fourier-transformed and infrared spectroscopy, and found to be very similar to those of natural bone. Drug release tests were performed under SOB in simulated body fluid (pH 7.8), and then under SOC in acetate buffer (pH 4.5) at 37.0±0.1 °C, and the process repeated twice. The device released almost no drug in SOB, but a significant amount in SOC. The drug release in SOC was not proportional to the number of macro pores in the first test, but was in the second. The device showed dissolution medium-responsive drug release.     

Controlling liposomal drug release with low frequency ultrasound: mechanism and feasibility

The ability of low-frequency ultrasound (LFUS) to release encapsulated drugs from sterically stabilized liposomes in a controlled manner was demonstrated. Three liposomal formulations having identical lipid bilayer compositions and a similar size ( approximately 100 nm) but differing in their encapsulated drugs and methods of drug loading have been tested. Two of the drugs, doxorubicin and methylpredinisolone hemisuccinate, were remote loaded by transmembrane gradients (ammonium sulfate and calcium acetate, respectively). The third drug, cisplatin, was loaded passively into the liposomes. For all three formulations, a short exposure to LFUS (<3 min) released nearly 80% of the drug. The magnitude of drug release was a function of LFUS amplitude and actual exposure time, irrespective of whether irradiation was pulsed or continuous. Furthermore, no change in liposome size distribution or in the chemical properties of the lipids or of the released drugs occurred due to exposure to LFUS. Based on our results, we propose that the mechanism of release is a transient introduction of porelike defects in the liposome membrane, which occurs only during exposure to LFUS, after which the membrane reseals. This explains the observed uptake of the membrane-impermeable fluorophore pyranine from the extraliposomal medium during exposure to LFUS. The implications of these findings for clinical applications of controlled drug release from liposomes are discussed.     

pH敏感型聚谷氨酸/透明质酸基互穿网络医用水凝胶的制备及表征

生物材料是推动生物医学领域日新月异变化的基石,医用水凝胶作为重要成员,近年来表现出蓬勃发展的态势。文章介绍了一种新型可注射的、以生物相容性方法交联的聚谷氨酸(Poly (γ-glutamic acid), PGA)/透明质酸(Hyaluronic acid, HA)复合水凝胶。研究首先采用EDC/NHS方法合成了酪胺(Tyramine,Ty)接枝聚谷氨酸的PGA-Ty前体大分子及半胱胺(Cysteamine, CA)修饰透明质酸的HA-CA前体大分子。两种前体大分子的结构分别使用核磁和红外进行了确证。得到的两种前体大分子在低浓度双氧水和辣根过氧化物酶(Horseradish Peroxidase, HRP)的共同作用下,于水相中交联得到互穿网络(Interpenetrating Network, IPN)水凝胶。实验对IPN水凝胶样品的系列性能,如平衡含水量、内部形貌、酶降解速率以及力学性能等进行了测试,并选取了盐酸四环素为药物模型对凝胶的体外药物释放行为、体外抗菌效果进行了测评。凝胶材料的细胞毒性及凝胶支架对细胞3D培养的效果证明其生物相容性优异,体外包埋的细胞经72h培养,未表现出明显细胞毒性。系列数据证明,该种水凝胶可以设计成为pH敏感型的药物控释载体材料,并因其良好的生物相容性,也有作为细胞支架、创伤辅料等其它生物医用材料的潜力。     

Dynamic Release of Propranolol HCl from Cationic Ion–Exchanger–Loaded Calcium Alginate Beads

The dynamic release of drug propranolol HCl from the propranolol HCl–resin complex (PRC) loaded calcium alginate beads has been studied in the buffer media of pH 1.2 at the physiological temperature 37°C. The PRC encapsulated beads demonstrated nearly 58.04% release while naked PRC particles released 98.00% drug in 24 h in the gastric fluid. The amount of drug released was found to increase with and decrease in the amount of sodium alginate in the beads. Similarly, with the increase in the amount of entrapped PRC particles within the beads, the quantity of drug released was also observed to increase. The degree of crosslinking of beads also affected the release kinetics. Interestingly, the release from naked PRC particles followed ‘first‐order’ kinetics while PRC particles, entrapped in calcium–alginate beads, exhibited ‘diffusion controlled’ release behavior as indicated by liner nature of fractional release vs. √t plot.     

pH‐responsive polymer core–shell nanospheres for drug delivery

Stimuli‐responsive polymer nanoparticles are playing an increasingly more important role in drug delivery applications. However, limited knowledge has been accumulated about processes which use stimuli‐responsive polymer nanospheres (matrix nanoparticles whose entire mass is solid) to carry and deliver hydrophobic therapeutics in aqueous solution. In this research, pyrene was selected as a model hydrophobic drug and a pyrene‐loaded core‐shell structured nanosphere named poly(DEAEMA)‐poly(PEGMA) was designed as a drug carrier where DEAEMA and PEGMA represent 2‐(diethylamino)ethyl methacrylate and poly(ethylene glycol) methacrylate, respectively. The pyrene‐loaded core‐shell nanospheres were prepared via an in situ two‐step semibatch emulsion polymerization method. The particle size of the core‐shell nanosphere can be well controlled through adjusting the level of surfactant used in the polymerization where an average particle diameter of below 100 nm was readily achieved. The surfactant was removed via a dialysis operation after polymerization. Egg lecithin vesicles (liposome) were prepared to mimic the membrane of a cell and to receive the released pyrene from the nanosphere carriers. The in vitro release profiles of pyrene toward different pH liposome vesicles were recorded as a function of time at 37 °C. It was found that release of pyrene from the core‐shell polymer matrix can be triggered by a change in the environmental pH. In particular the pyrene‐loaded nanospheres are capable of responding to a narrow window of pH change from pH = 5, 6, to 7 and can achieve a significant pyrene release of above 80% within 90 h. The rate of release increased with a decrease in pH. A first‐order kinetic model was proposed to describe the rate of release with respect to the concentration of pyrene in the polymer matrix. The first‐order rate constant of release k was thus determined as 0.049 h^?1 for pH = 5; 0.043 h^?1 for pH = 6; and 0.035 h^?1 for pH = 7 at 37 °C. The release of pyrene was considered to follow a diffusion‐controlled mechanism. The synthesis and encapsulation process developed herein provides a new approach to prepare smart nanoparticles for efficient delivery of hydrophobic drugs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4440–4450     

Ultrasound-Triggered Delivery of Iproplatin from Microbubble-Conjugated Liposomes

The Pt^IV prodrug iproplatin has been actively loaded into liposomes using a calcium acetate gradient, achieving a 3-fold enhancement in drug concentration compared to passive loading strategies. A strain-promoted cycloaddition reaction (azide- dibenzocyclooctyne) was used to attach iproplatin-loaded liposomes L(Pt) to gas-filled microbubbles (M), forming an ultrasound-responsive drug delivery vehicle [M−L(Pt)]. Ultrasound-triggered release of iproplatin from the microbubble-liposome construct was evaluated in cellulo. Breast cancer (MCF-7) cells treated with both free iproplatin and iproplatin-loaded liposome−microbubbles [M−L(Pt)] demonstrated an increase in platinum concentration when exposed to ultrasound. No appreciable platinum uptake was observed in MCF-7 cells following treatment with L(Pt) only or L(Pt)+ultrasound, suggesting that microbubble-mediated ultrasonic release of platinum-based drugs from liposomal carriers enables greater control over drug delivery.     

Conjugation of pectin biopolymer with Au-nanoparticles as a drug delivery system: Experimental and DFT studies

In the present study, pectin-coated gold nanoparticles (GNPs) were used as a candidate for curcumin drug delivery. The effect of the size of synthesized GNPs was examined, as an important factor on the yield of drug delivery. For this purpose, three different sizes of GNPs were first synthesized using a chemical method. The synthesized nanoparticles were then coated with pectin biopolymer. Finally, curcumin drug was loaded in a pectin@GNPs complex. Various methods such as UV–vis spectrophotometry, dynamic light scattering, scanning electron microscopy and Fourier-transform infrared spectroscopy were used to characterize the synthesized GNPs and pectin@GNPs. The encapsulation efficiency and the release percentage of the drug were calculated for two different pH values. Further, an antibacterial study was conducted. The results revealed that 100 nm GNPs had the highest encapsulation efficiency. An investigation of the release rate of curcumin drug at 37°C for 48 h indicated that the amount of drug released was higher in acidic pH than at pH 7.4 with a slow release rate. The electronic structure and the adsorption properties of pectin–GNPs complex were examined using the density functional theory method.