Amphiphilic Drug Delivery Microcapsules via Layer-by-Layer Self-Assembly

A strategy to incorporate and release the amphiphilic drugs of doxorubicin (DOX) and ibuprofen (IBU) in the same microcapsules is introduced, A layer-by-layer (LbL) assembly of microcapsules with doxorubicin hydrochloride (DOX) or green fluorescent agent, hydrophilic fluorescein isothiocyanate (FITC), encapsulated in CaCO₃ microparticle templates, was conducted via alternatively depositing sodium carboxymethyl cellulose (CMC) and chitosan (CHI) onto IBU or red fluorescent agent (hydrophobic Nile Red) preloaded poly-L-lactide (PLLA) coated magnetic Fe₃O₄-DOX-loaded CaCO₃ (or FITC-loaded) templates. The structure, morphology, composition, magnetic properties and drugs distribution of the obtained microcapsules were characterized by nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), zeta potential analysis, thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM) and confocal laser scanning microscopy. The fluorescent agents loading of FITC and Nile Red were confirmed by observations using confocal laser scanning microscopy. Fluorescence observations showed that the DOX was distributed both in the walls and in the cavities of the microcapsules, while IBU was present in the capsule wall. The in–vitro release of the dual drugs, DOX and IBU, from the microcapsules with different numbers of CHI and CMC layers was characterized. A tunable amount of drug release was achieved by changing the number of layers. The release study indicated that the LBL microcapsules exhibited better sustained release capacity compared to the uncoated microcapsules. The microcapsules inherited a strong magnetic property from the Fe₃O₄ nanoparticles, sufficient for targeting and magnetic hyperthermia drug delivery systems.     

MRI评价药物投递性能方法研究

采用MRI评价自制肝组织特异性非离子型高分子磁共振造影剂在小鼠体内药物投递效果. 分别在注射造影剂后0.1 h、6 h、12 h、24 h及7天采集磁共振T₁加权图像. 所有扫描均在1.5T临床磁共振成像仪上完成, 以固定体线圈为射频发射线圈, 三英寸圆形表面线圈为信号接收线圈. 数据分析前采用线圈非均匀性校正和信号非稳定性校正进行预处理. 实验结果显示,线圈空间敏感性校正使得小鼠组织图像信号强度空间更加均匀,稳定性校正后使得图像数据更加准确可靠,MRI是一种在体评价顺磁性标记高分子化合物药物投递效果的有效方法.     

具有双重治疗机制的磁性纳米无定型氧化铁基药物递送系统

合成一种具有pH响应性的聚乙二醇(PEG)修饰无定形介孔氧化铁纳米粒子(AFe-PEG). 这种纳米粒子可以高效负载药物分子如阿霉素(DOX),构成新型多功能AFe-PEG/DOX药物递送体系. DOX的负载率高达948 mg/g-纳米粒子. 在酸性溶液中,AFe-PEG/DOX纳米粒子不仅可以有效释放DOX,同时可以释放Fe离子进行Fenton反应,将H₂O₂转变成·OH自由基. 体外实验结果表明,AFe-PEG/DOX纳米粒子对HeLa细胞同时具有化疗和化学动力学疗法的疗效. 同时,由于AFe-PEG/DOX 纳米粒子本身的磁性,使其在外部磁场中的细胞内化效率也得到了提高.     

Multifunctional Magnetic Nanomedicine Drug Delivery and Imaging-Based Diagnostic Systems

Magnetically guided drug transportation is a technique in which magnetic pharmaceutical transporters in organisms are controlled by applied magnetic forces to deliver drugs to the desired location. Different magnetic drug delivery systems (MDDSs) are developed to treat a variety of illnesses, particularly cancer and neurological disorders. However, a unique magnetic setup is required in each application for an effective magnetically guided drug aiming to direct the drug-carrying nanocarriers to the intended area. The current and future perspectives of MDDS are investigated in this study by considering their biological functions, deliverable efficiency, complexity, and the nature of the externally applied magnetic field. Despite the fact that MDDSs have low cytotoxicity, regulated magneto reactivity, extended circulation lifespan, and high surface stability, very few clinical studies have been conducted to date in order to achieve optimized therapeutic efficacy before entering the market. In recent studies, the development of novel magnetic medication transporting carriers is preferred over direct magnetic medication administration. Better functional magnetic targeting technologies are required for such breakthroughs to enter clinical trials. Because MDDSs are unlikely to work in all clinical situations, more focused research is needed to replace or improve the strategy for treating multiple illnesses.     

Modeling of Drug Release from a Novel Temperature-Responsive Phase-Transient Drug Delivery System in Cylindrical Coordinates

In this study, a novel phase-transient multilayer drug delivery system responsive to a unique stimulus, i.e., temperature, was introduced in cylindrical coordinates. The system is composed of three individual sections, including the drug core, phase-transient intermediate layer, and protecting polymeric coverage. The phase-transient layer gives smartness to the system and creates an “On-Off” release profile with increasing or decreasing the environmental temperature around the melting point of the layer. The “On-Off” response of the system was mathematically modeled by analyzing the heat and mass transfer equations in the pseudo-steady state and the effects of various parameters on the performance of the system were investigated. The modeling results showed the intensity of the effects of different kinds of factors, including the geometrical characteristics of the system (e.g., the radius of the drug core and the thicknesses of the intermediate and polymeric layers), the physical properties of the matrix materials (e.g., the thermal conductivities and diffusion coefficients of the intermediate and polymeric layers), and the operation conditions, on the response time lag and release kinetics of the presented system. The obtained results in this study predict methods to prepare multilayer temperature-responsive drug delivery systems with desired and optimized responses (e.g., with a short lag time) for practical biomedical applications.     

Mathematical Modeling of Drug Release in a Phase-Transient Temperature-Responsive Drug Delivery System in Spherical Coordinates

Abstract

A sphere-shaped drug delivery system responsive to temperature, as a unique external stimulus, was introduced and its performance mathematically studied at the pseudo-steady state. The system is composed of three individual sections, including the drug core, phase-transient intermediate shell, and protective polymeric shell. An ON-OFF release of drug could be achieved by increasing or decreasing the environmental temperature around the melting point of the intermediate shell and the smartness of system is due to the solid-liquid phase transition of this shell. The ON-OFF response of the system was mathematically modeled by solving the governing heat and mass transfer equations at the pseudo-steady state. The results showed the lag time of the system in the ON state, the cumulative released drug in the ON state and the fractional undesired release of drug in the OFF state are strongly under the influences of different kinds of factors, including the geometrical characteristics of the system (e.g., the radius of the drug core and the thicknesses of the intermediate and polymeric shells), the physical properties of the system (e.g., the thermal conductivities and diffusion coefficients of the intermediate and polymeric shells), and the environmental and operation conditions.     

Ellipsometry and TIRF Studies of Adsorption Processes in Parenteral Drug Delivery

Ellipsometry and total internal reflection fluorescence spectroscopy(TIRF) were used for investigating adsorption processes of relevance forparenteral administration of colloidal drug carriers. Emphasis is put ondiscussing the effects of both protein and surface properties on theadsorption of serum proteins at phospholipid and other surfaces.Furthermore, the adsorption from multicomponent protein systems, such asblood, is addressed, and both competitive and associative adsorptionphenomena discussed. The correlation between effects of the drug carriersurface properties on the serum protein adsorption and the circulation timeand tissue distribution of colloidal drug carriers is also addressed.Finally, the potential of ellipsometry in another adsorption process ofmajor importance for phagocytosis, i.e., the adsorption of colloidalparticles to macroscopic or mesoscopic surfaces, is indicated byinvestigations of the adsorption of oil-in-water emulsion droplets atsilica.     

Multifunctional Polymer‐Coated Carbon Nanotubes for Safe Drug Delivery

Although progress in the use carbon nanotubes in medicine has been most encouraging for therapeutic and diagnostic applications, any translational success must involve overcoming the toxicological and surface functionalization challenges inherent in the use of such nanotubes. Ideally, a carbon‐nanotube‐based drug delivery system would exhibit low toxicity, sustained drug release, and persist in circulation without aggregation. Here, carbon nanotubes (CNTs) coated with a biocompatible block‐co‐polymer composed of poly(lactide)‐poly(ethylene glycol) (PLA‐PEG) are reported to reduce short‐term and long‐term toxicity, sustain drug release of paclitaxel (PTX), and prevent aggregation. The copolymer coating on the surface of CNTs significantly reduces in vitro toxicity. Moreover, the coating reduces the in vitro inflammatory response. Compared to non‐coated CNTs, in vivo studies show no long‐term inflammatory response with CNT coated with PLA‐PEG (CLP) and the surface coating significantly decreases acute toxicity by doubling the maximum tolerated dose in mice. In vivo biodistribution and histology studies suggest a lower degree of aggregation in tissues.     

两亲性类树枝状聚合物的合成与药物控释

结合阴离子开环聚合方法合成了内壳为聚(乙氧基乙基缩水甘油醚),外层为聚环氧乙烷的两亲性类树枝状嵌段共聚物PEEGE-G2-b-PEO(OH)₁₂. 使用核磁共振氢谱以及凝胶渗透色谱等表征了中间产物和目标产物. 选择阿霉素作为实验药物,研究了该聚合物的载药和控释行为. 聚合物的载药率和包覆效率分别为13.07%和45.75%,体外释放试验表现为持续性的释放,并受到释放介质pH影响.     

pH-Sensitive Poly(Vinyl Alcohol)/Sodium Carboxymethylcellulose Hydrogel Beads for Drug Delivery

A series of pH-sensitive hydrogel beads were prepared composed of poly(vinyl alcohol) (PVA) and sodium carboxymethylcellulose (CMC) by using Fe³⁺ crosslinking and freeze-thawing (FT) cycle techniques. The mixed solution of CMC and PVA was firstly crosslinked with Fe³⁺ to form beads and then subjected to freezing-thawing cycles for further crosslinking. The formation of hydrogel was confirmed by Fourier transform infrared spectroscopy (FTIR). The gelling rate in ferric solution and the swelling and pH-senstive properties of the hydrogel beads were investigated. The encapsulation efficiency and in-vitro release properties of beads were also evaluated using Bovine serum albumin as model drug. The pH sensitivity and the release rate increased with increasing CMC content. These results suggest that the PVA/CMC hgdrogel beads should be useful as pH-sensitive drug delivery systems for bioactive agents.     

Selective Enrichment of Polydopamine in Mesoporous Nanocarriers for Nuclear‐Targeted Drug Delivery

Small particle size and strong host–guest interactions are prerequisites in the field of nuclear‐targeting nanocarriers for overcoming the multidrug resistance of cancer cells. A novel scheme of synthesizing hybrid organic–inorganic nanocarriers with mesopores is introduced to enhance the delivery efficiency of therapeutic drugs. Specifically, inorganic silica and organic polydopamine (PDA) are integrated inside the pore framework by the assistance of organic silanes terminated by amino/thiol groups. Silica‐etching by hydrothermal treatment leads to the selective enrichment of bioadhesive PDA and size reductions for the hybrids (to ≈30 nm). Interestingly, a high drug loading capacity (523 µg mg⁻¹ for doxorubicin hydrochloride), as well as pH/ glutathione dual‐responsive drug release properties, are realized by the nanocarriers, owing to their high surface area (825 m² g⁻¹) and the π‐stacking and/or hydrophobic–hydrophobic interactions stemming from PDA. More importantly, the conjugation of TAT peptide facilitates the intranuclear localization of the nanocarriers and the release of the encapsulated drugs directly within the nucleoplasm of the multidrug resistant MCF‐7/ADR cancer cells. Therefore, these results provide a controllable method of engineering high‐surface‐area nanocarriers with bioadhesive polymers on the pore surface for advanced drug delivery applications.     

Temperature and Redox Dual‐Responsive Biodegradable Nanogels for Optimizing Antitumor Drug Delivery

The strategy to efficiently deliver antitumor drugs via nanocarriers to targeted tumor sites and achieve controllable drug release is attracting great research interest in cancer therapy. In this study, a novel type of disulfide‐bonded poly(vinylcaprolactam) (PVCL)‐based nanogels with tunable volume phase transition temperature and excellent redox‐labile property are prepared. The nanogels are hydrophilic and swell at 37 °C, whereas under hyperthermia (e.g., 41 °C), the nanogels undergo sharp hydrophilic/hydrophobic transition and volume collapse, which enhances the cellular uptake and drug release. The incorporation of disulfide bond linkers endows the nanogels with an excellent disassembly property in reducing environments, which greatly facilitates drug release in tumor cells. Nanogels loaded with doxorubicin (DOX) (DOX‐NGs) (DOX‐NGs) are stable in physiological conditions with low drug leakage (15% in 48 h), while burst release of DOX (92% in 12 h) can be achieved in the presence of 10 × 10^?3 m glutathione and under hyperthermia. The DOX‐NGs possess improved cell killing efficiency under hyperthermia (IC₅₀ decreased from 1.58 μg mL^?1 under normothermia to 0.5 μg mL^?1). Further, the DOX‐NGs show a pronounced tumor inhibition rate of 46.6% compared with free DOX, demonstrating that this new dual‐responsive nanogels have great potential as drug delivery carriers for cancer therapy in vivo.     

海藻酸改性的空心Fe3O4纳米颗粒的制备与应用

不使用任何模板一步制得空心Fe₃O₄纳米颗粒,然后将海藻酸钠嫁接在氨基化的空心Fe₃O₄表面,再利用海藻酸盐与钙离子的作用,在空心Fe₃O₄表面形成一个凝胶化层,制得海藻酸盐凝胶化的空心Fe₃O₄纳米颗粒,粒径约为400～500 nm．采用TEM、XRD、XPS、VSM等手段对纳米微球进行表征．VSM表征结果表明在室温下样品磁性材料为超顺磁性．改性Fe₃O₄纳米颗粒成功地用于柔红霉素的载负和缓释,最大载负率和载药量分别为28.4%和14.2%．缓释结果表明,海藻酸盐凝胶化层的存在,能更有效控制柔红霉素缓慢地释放．