介孔生物活性玻璃装载和释放抗癌药物表阿霉素的研究

将介孔58S生物活性玻璃(m58S)作为抗癌药物载体评价了其对表阿霉素的装载量和释放性能. 实验结果表明, m58S对亲水性药物表阿霉素的药物装载量为40%, 是普通溶胶-凝胶58S生物活性玻璃的3倍多, 并且具有更长效的缓释特性. 研究还发现释放介质的pH值对表阿霉素的释放速率有很大影响, pH值越低, 表阿霉素分子从载体材料中释放出的速率越快. 因此, 介孔生物活性玻璃是一种高效的药物缓释载体, 且药物释放速率受释放介质pH值影响, 有望成为药物控释型骨修复材料.     

介孔硼硅酸盐玻璃微球药物载体的制备及其性能表征

介孔二氧化硅微粒具有化学稳定性好、比表面积大和表面易修饰等特点, 作为药物载体具有良好的应用前景, 但其缺乏生物活性且生物降解缓慢等在一定程度上限制了它的应用领域。为克服这些缺陷, 寻找合适的药物载体已成为重要研究方向。与纯二氧化硅相比, 硼硅酸盐玻璃具有良好的生物活性和更高的降解速率。基于此, 本研究尝试合成介孔硼硅酸盐玻璃微球(MBGMs), 并表征了其在负载和释放抗肿瘤药物盐酸阿霉素(DOX)过程中的载体特性和材料降解引发的各种功能性离子的释放行为。结果表明BMGMs具有约25 mg/g的DOX负载量,引入硼不仅可以调控MBGMs的化学活性和降解速率, 而且较高硼含量的MBGMs可促进酸性条件下的药物释放, 具有一定的酸性响应性。此外, MBGMs可在模拟体液中释放SiO₄^4-、BO₃^3-和Ca²⁺等有益骨组织生长的功能性离子, 并诱导生成羟基磷灰石, 具备良好的离子缓释能力和体外矿化活性。因此, MBGMs作为一种新颖的药物载体材料, 既可作为药物和功能离子的双重负载, 又具有良好的生物活性和降解特性, 在病理性骨缺损修复领域具有良好的应用前景。     

载替考拉宁治疗骨髓炎症的硼酸盐生物玻璃药物载体的研究

本实验制备了用于治疗骨髓炎的以硼酸盐生物活性玻璃为基体负载抗菌素的药物载体系统.此药物载体系统的固相为硼酸盐生物玻璃,其组成为6Na2O-8K2O-8MgO-22CaO-54B2O3-2P2O5(mol%);液相为壳聚糖/柠檬酸/葡萄糖溶液;所载药物为水溶性药物-替考拉宁.在体外的磷酸盐缓冲溶液(PBS)的浸泡实验中,对载体系统中的药物释放、机械性能以及玻璃基体的生物降解性进行了测试,通过高效液相色谱仪测定浸泡溶液中替考拉宁的含量.实验表明,这种硼酸盐生物活性玻璃基药物载体系统中的药物缓释可持续30d;其中,在缓释的第一周内药物缓释量仅达到72%.通过Peppas模型对药物缓释行为进行模拟,证明药物的释放过程符合F ick扩散定律.实验结果还表明,经XRD物相分析证实,这种硼酸盐生物玻璃基体在药物释放的过程中转化为羟基磷灰石(Hydroxyapatite,HA),显示出药物载体系统的体外生物活性.在以兔子为动物模型的体内实验中,药物载体系统治愈了兔子胫骨中的骨髓炎,而且又促进骨创伤处新骨的生成.实验证明,硼酸盐生物活性玻璃是一种既能负载抗菌素药物治疗骨髓炎,又能促进骨修复的优良的生物材料.     

高分子微胶囊药物释放体系

用高分子材料作为载体的高分子微胶囊和纳米级胶囊药物制剂不仅能控制药物以一定的速度释放 ,而且还可以对生物体的生理指标变化作出相应的反馈 ,因而可以制成靶向药物释放体系。文章较全面地综述了高分子微胶囊药物的制备技术和应用。阐述了高分子微胶囊的粒径、表面积、孔度、药物性能和药含量 ,以及高分子胶囊材料的性能对药物释放行为的影响。并对药物释放机理进行了简单扼要的陈述。     

聚乙烯吡咯烷酮用于药物递送载体材料的研究进展

高分子药物递送载体材料具有良好的生物相容性和生物可降解性,可以有选择性的释放药物,以提高药物利用率和降低药物的副作用,因此,高分子药物递送载体材料已成为当前的研究热点。聚乙烯吡咯烷酮(PVP)是一种绿色的高分子材料,具有优异的溶解性和低毒性,在医用材料领域具有广泛的应用。主要介绍了高分子药物递送载体材料的基本特性,并对聚乙烯吡咯烷酮的特性、合成、改性以及应用进行了较详细的论述,最后对其发展和应用前景进行了展望。     

聚β-羟基丁酸酯(PHB)在医学领域中的应用研究

简要介绍了生物降解聚合物聚β-羟基丁酸酯(PHB)的主要性能特点,着重评述了PHB在药物释放和组织工程方面的应用研究.并在药物释放方面介绍了利用PHB及其改性材料制成缓释微球作为药物缓释载体材料的研究;在组织工程方面综述了PHB在软骨、骨、心脏瓣膜等方面的应用研究进展.     

磁性水凝胶作为药物载体的应用研究进展

磁性水凝胶是一类同时具有磁性材料、高分子材料及水凝胶的性质特点的无机/有机复合材料。因具有优良的磁学性能及生物相容性,其作为新一代的药物载体可以实现磁响应、磁靶向及磁热疗等功能,在药物控制释放领域具有广阔的应用前景。对磁性水凝胶的制备方法及其在药物载体领域的研究情况进行了综述,详细介绍了磁性水凝胶作为药物载体的两种药物释放机理(ON/OFF模型及热敏释放原理),及其在磁靶向药物控释、磁热疗和磁共振成像方面的应用研究现状。     

介孔生物玻璃/磷酸钙骨水泥多级孔复合支架的制备及其载药特性研究

采用离心法将介孔生物活性玻璃(MBG)和磷酸钙骨水泥(CPC)高效复合制备出介孔/大孔多级孔复合支架材料, 评价了其对抗癌药物阿霉素的装载及释放性能。实验结果表明, 采用离心法能在大孔支架CPC内有效负载大量的介孔生物活性玻璃, 使其比表面积高达100.1 m²/g, 负载量达47.2%, 而采用传统浸渍法则不能将MBG粉体材料负载于CPC支架上。载药实验发现离心法制备的介孔/大孔复合支架对阿霉素的装载量达到了46 mg/g, 是普通大孔CPC支架的11.5倍, 且在体外具有药物缓释的特性。     

用于药物载体系统的多糖材料的修饰方法

癌症是一种致死率极高的全球性疾病。迄今为止,化学药物疗法仍然是治疗癌症最为直接有效的手段,然而,目前采用的化疗药物通常不具备特异性,在杀死肿瘤细胞的同时也会对正常组织细胞带来严重的毒副作用。因此,如何安全有效地将抗癌药物输送至肿瘤组织并增强药物在肿瘤细胞内的吸收是当今癌症治疗领域急需解决的难题。药物控制释放技术通过功能化载体材料对药物进行负载,对药物释放位点及速率进行控制,从而实现降低药物毒副作用、提高药物生物利用度的目的。载体材料是实现药物控制释放的技术关键,因此,设计并开发多功能药物载体已成为该领域的研究热点。理想的药物载体通常需具备高稳定性、低生物毒性、非免疫原性及组织靶向性等特点。目前,无机纳米粒子、脂质体、水凝胶、聚合物胶束、微囊等多种药物载体已被广泛应用于癌症的诊断及治疗研究。基于天然高分子材料的药物载体因具有优良的生物相容性及临床应用前景受到了众多研究者的青睐,因此,对天然高分子材料进行化学修饰构建药物载体也已成为药物控释领域的重要研究方向。多糖是一类具有良好生物降解性及生物相容性的天然高分子材料,具有在自然界中种类丰富、水溶性高、容易进行化学修饰等优点。多糖的分子结构中含有大量的活性反应基团(羟基、氨基和羧酸基团等),经过特定的化学修饰,改变其物理或化学性质可形成水凝胶、胶束、囊泡等结构,其作为药物载体在生物材料领域具有潜在的应用价值。目前,常用的多糖修饰方法包括疏水性分子接枝、醛基化改性、原位二硫键修饰等。修饰后形成的基于多糖的药物载体具有药物释放速度可控、生物安全性好等特性,并且可以实现改变药物进入人体的方式及在体内的分布,被动或主动靶向将药物输送到特定的作用部位,达到靶向治疗的目的。本文综述了多种对天然多糖进行化学修饰,构建水凝胶、胶束及囊泡类多糖药物载体的方法,并简要讨论了基于多糖的药物载体在生物医学领域的研究前景及应用价值。     

药物控制释放用高分子载体的研究进展

综述了高分子药物控制释放体系的机理和种类,其中重点介绍了可控生物降解高分子载体的设计与研究,以及天然高分子载体、合成高分子载体和以亲水凝胶为载体的药物控制释放体系的制备与应用,并通过介绍双亲性聚合物对其前景进行了预测。     

In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites

Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.     

Hollow Mesoporous Silica Nanocarriers with Multifunctional Capping Agents for In Vivo Cancer Imaging and Therapy

Efficient drug loading and selectivity in drug delivery are two key features of a good drug‐carrier design. Here we report on such a drug carrier formed by using hollow mesoporous silica nanoparticles (HMS NPs) as the core and specifically designed multifunctional amphiphilic agents as the encapsulating shell. These nanocarriers combine the advantages of the HMS NP core (favorable physical and structural properties) and the versatility of an organic‐based shell (e.g., specificity in chemical properties and modifiability). Moreover, both the properties of the core and the shell can be independently varied. The varied core and shell could then be integrated into a single device (drug carrier) to provide efficient and specific drug delivery. In vitro and in vivo data suggests that these drug nanocarriers are biocompatible and are able to deliver hydrophobic drugs selectively to target tumor cells. After the break of the pH‐labile linkages in the shell, the drug payload can be released and the tumor cells are killed.     

Local antibiotic delivery systems for the treatment of osteomyelitis – A review

Osteomyelitis, an inflammatory process accompanied by bone destruction, is caused by infective microorganisms. The high success rates of antimicrobial therapy by conventional routes of administration in controlling most infectious diseases have not yet been achieved with osteomyelitis for several reasons. Local and sustained availability of drugs have proven to be more effective in achieving prophylactic and therapeutic outcomes. This review introduces osteomyelitis – its present options for drug delivery and their limitations, and the wide range of carrier materials and effective drug choices. Local drug delivery for osteomyelitis is a topic of importance for more than 20 years. Carrier materials used for local delivery of antibiotics may be classified as nonbiodegradable and biodegradable. Commonly used non biodegradable carrier materials are polymethyl methacrylate (PMMA), Acrylic beads, PMMA bone cement etc. and biodegradable materials are hydroxyapatite block, bioactive glass ceramics, collagen sponge, polylactide/ployglycolide implants. Both the systems release antibiotic at concentrations exceeding the minimum inhibitory concentrations (MICs) for the most common pathogens involved in osteomyelitis without causing any adverse systemic effects although non biodegradable beads are to be removed from the surgical site after completion of antibiotic release.     

淀粉基口服结肠靶向给药控释载体

通过合理改性来调控淀粉的消化性能,使其具有不被上消化道消化、但能够被结肠微生物酵解的特性,则可用作口服结肠靶向药物控释载体.综述了淀粉的结构、消化特性、影响淀粉消化特性的因素及其在口服结肠靶向药物控释载体中的应用前景.     

Methods for reduction of cohesive forces between carrier and drug in DPI formulation

Dry powder inhaler (DPI) has become a well accepted drug delivery for pulmonary system to treat many related diseases including symptomatic and life threatening diseases. Successful delivery of dry powder to the lung requires careful consideration of powder production process, formulation and inhaler device. The formulation of DPI mostly comprises of lactose as a carrier for drug delivery. In DPI formulation, particulate interactions within the formulation govern both the drug dissociation from carrier particles and the disaggregation of drug into primary particles with a capacity to penetrate deep into lung. Two contradictory requirements must be fulfilled for this type of dry powder formulation. On one hand, adhesion between carrier and drug must be sufficient for the blend drug/carrier to be stable. On the other hand, adhesion drug/carrier has to be weak enough to enable the release of drug from carrier during patient inhalation. Thus the carrier use restricted due to detachment problem. Different methods are proposed to reduce the cohesive forces between drug and carrier to desired level. Various studies conducted for understanding the mechanism of deposition into lungs and making formulation with optimum carrier drug cohesive force. This review provides information on various processes involved in reducing the cohesive forces between drug and carrier, to a required level.     

Development of drug adsorbates onto soluble inorganic silicate glass surface: example with acetaminophen

A ternary melt-derived inorganic glass system (Igl) of composition corresponding to 62SiO₂, 35Na₂O, 3Al₂O₃ (wt.%) has been formulated and studied as a drug carrier. The [Al₂O₃/Na₂O] ratio is less than one and the aluminium ion is a network former that retards the glass dissolution. The processing conditions lead to a brittle, easily grinding, amorphous product. The Igl structure was proven by IR-spectroscopy, energy-dispersive spectrometry, X-ray diffraction, scanning electron microscopy. A very important fact established is that the Igl corrosion (dissolution) is pH-dependent. Inorganic glass system was transformed into model acetaminophen (APH) adsorbate (APH/Igla 1:1(w/w)) with mild experimental conditions and evaluated as a drug carrier. No interactions between Igl and APH during the processing were proven. Besides, APH settles onto the glass surface as crystalline phase. A lower extent of corrosion, apparent solubility and delayed in vitro APH release from the adsorbate in water and artificial gastric juice in comparison to the samples untreated drug and APH/Iglm physical mixture were established. It is hypothesized that the glass decomposition products, formed into contact with a solvent, initiate interactions with APH at the glass/solution interface. Similar behaviour of the Igl and its drug adsorbates could be expected in gastro-intestinal tract.     

Resistant starch as a carrier for oral colon-targeting drug matrix system

In this study, a novel tablet of protein drug matrix for colon targeting was developed using resistant starch as a carrier prepared by pre-gelatinization and cross-linking of starch. The effects of pre-gelatinization and cross-linking on the swelling and enzymatic degradation of maize starch as well as the release rate of drug from the matrix tablets were examined. Cross-linked pre-gelatinized maize starches were prepared by double modification of pre-gelatinization and cross-linked with POCl₃, and bovine serum albumin was used as a model drug. For in vitro drug release assays, the resistant starch matrix tablets were incubated in simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid, respectively. The content of resistant starch and swelling property of maize starch were increased by pre-gelatinization and cross-linking, which retarded its enzymatic degradation. Drug release studies have shown that the matrix tablets of cross-linked pre-gelatinized maize starch could delivery the drug to the colon. These results indicate that the resistant starch carrier prepared by pre-gelatinization and cross-linking can be used for a potential drug delivery carrier for colon-targeting drug matrix delivery system.     

Pharmacological activity of ibuprofen released from mesoporous silica

Novel drug delivery systems (DDS) to improve the pharmacokinetic profile of hydrophobic drugs following oral administration are an area of keen interest in drug research. An ideal DDS should not adversely affect drug activity, be capable of delivering a therapeutic dose of drug, and allow homogenous drug loading and drug release. Mesoporous silica has been proposed for this application, with ibuprofen employed as the model drug. It was hypothesised that mesoporous silica MCM-41 is capable of delivering a pharmacologically therapeutic dose of ibuprofen. Ibuprofen-loaded MCM-41 can be prepared reproducibly at a drug to carrier ratio of 30% (wt/wt). The release profile was seen to be 90% within 2 h. Initial assessment of COX-1 inhibitory activity suggests the absence of adverse effects attributable to drug-carrier interaction. The results of this study provide further evidence in support of the proposed use of mesoporous silica in drug delivery.     

Glycyrrhetinic Acid Functionalized Graphene Oxide for Mitochondria Targeting and Cancer Treatment In Vivo

Mitochondria‐mediated apoptosis (MMA) is a preferential option for cancer therapy due to the presence of cell‐suicide factors in mitochondria, however, low permeability of mitochondria is a bottleneck for targeting drug delivery. In this paper, glycyrrhetinic acid (GA), a natural product from Glycyrrhiza glabra, is found to be a novel mitochondria targeting ligand, which can improve mitochondrial permeability and enhance the drug uptake of mitochondria. GA‐functionalized graphene oxide (GO) is prepared and used as an effective carrier for targeted delivery of doxorubicin into mitochondria. The detailed in vitro and in vivo mechanism study shows that GA‐functionalized GO causes a decrease in mitochondrial membrane potential and activates the MMA pathway. The GA‐functionalized drug delivery system demonstrates highly improved apoptosis induction ability and anticancer efficacy compared to the non‐GA‐functionalized nanocarrier delivery system. The GA‐functionalized nanocarrier also shows low toxicity, suggesting that it can be a useful tool for drug delivery.     

Self‐Assembly of an Amphiphilic Janus Camptothecin–Floxuridine Conjugate into Liposome‐Like Nanocapsules for More Efficacious Combination Chemotherapy in Cancer

The combination of camptothecin (CPT) and fluoropyrimidine derivatives acts synergistically at a 1:1 molar ratio. Practically, the greatest challenge is the development of a single liposomal formulation that can both encapsulate and maintain this drug combination at an exact 1:1 ratio to achieve coordinated pharmacokinetics. Consequently, a new type of liposome‐like nanocapsule (NC) is developed from a highly symmetric Janus camptothecin–floxuridine conjugate (JCFC) amphiphile, which is synthesized by coupling two hydrophobic CPT molecules and two hydrophilic floxuridine (FUDR) molecules to multivalent pentaerythritol via a hydrolyzable ester linkage. JCFC NCs possess remarkably high drug‐loading contents, and no premature release because of the highly stable co‐delivery of the drug combination without the need for any carrier. It is shown that JCFC NCs consistently provide synergy and avoid antagonism in a broad panel of tumor cell lines. In vivo delivery of JCFC NCs leads to longer blood retention half‐life, higher tumorous accumulation and cellular uptake of drugs, and greatly enhanced efficacy in murine tumor models compared to CPT, FUDR, and CPT + FUDR. This liposomal strategy can be extended to other hydrophilic and hydrophobic anticancer drugs that are coupled to pentaerythritol to self‐assemble into nanocapsules for drug self‐delivery, pointing to potential clinical translation in near future.