Aspirin attenuates the anti-inflammatory effects of theophylline via inhibition of cAMP production in mice with non-eosinophilic asthma

Theophylline is commonly used to treat severe asthma and chronic obstructive pulmonary disease (COPD) characterized by non-eosinophilic inflammation. Acetyl salicylic acid (ASA) is one of the most widely used medications worldwide, but up to 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma. A non-eosinophilic asthma mouse model was induced by airway sensitization with lipopolysaccharide-containing allergen and then challenged with allergen alone. Therapeutic intervention was performed during allergen challenge. Theophylline inhibited lung inflammation partly induced by T_h1 immune response. ASA attenuated the beneficial effects of theophylline. However, co-administration of the ASA metabolite salicylic acid (SA) showed no attenuating effect on theophylline treatment. The therapeutic effect of theophylline was associated with increase in cAMP levels, which was blocked by co-treatment of theophylline and ASA. ASA co-treatment also attenuated the anti-inflammatory effects of a specific phosphodiesterase 4 inhibitor. These results demonstrate that ASA reverses anti-inflammatory effects of theophylline, and that ASA exerts its adverse effects through the inhibition of cAMP production. Our data suggest that ASA reverses lung inflammation in patients taking theophylline, although clinical evidence will be needed.     

Biodegradable amphiphilic block copolymers containing functionalized PEO blocks:Controlled synthesis and biomedical potentials

A series of controllable amphiphilic block copolymers composed of poly(ethylene oxide)(PEO) as the hydrophilic block and poly(ε-caprolactone)(PCL) as the hydrophobic block with the amino terminal group at the end of the PEO chain(PCL-b-PEO-NH2) were synthesized.Based on the further reaction of reactive amino groups,diblock copolymers with functional carboxyl groups(PCL-b-PEO-COOH) and functional compounds RGD(PCL-b-PEO-RGD) as well as the triblock copolymers with thermosensitive PNIPAAm blocks(PCL-b-PEO-b-P...     

离子交换树脂药物载体在给药系统中的应用

离子交换树脂作为药物传递系统的有效载体,由于具有多种优良特性,已经受到药剂学家们的高度关注。本文就缓释、控释给药、靶向给药、离子导入透皮、鼻腔、眼部给药、胃漂浮剂给药、掩盖药物苦味和脉冲给药等方面在药剂学中的应用研究进行了概述。     

庆大霉素对羟基磷灰石/壳聚糖复合材料性能的影响

羟基磷灰石/壳聚糖-庆大霉素(HA/CS-G)缓释材料为骨髓炎的定点缓释给药提供了一种有效的局部药物缓释体系。为了研究抗生素对羟基磷灰石/壳聚糖材料性能的影响,采用共沉淀法制备了HA/CS-G缓释材料。利用红外光谱(IR)、X射线衍射(XRD)和扫描电子显微镜(SEM)对材料进行了表征。以不载药的羟基磷灰石/壳聚糖(HA/CS)为对照,研究了庆大霉素对HA/CS复合材料抑菌性能、力学性能和降解性能等的影响。实验结果表明,HA/CS-G有良好的抑菌效果。负载庆大霉素后HA/CS的机械强度明显增强,而材料的降解速率有所下降。本文采用的二次成型技术显著增大了材料的机械强度。     

Molecular Nanoworm with PCL Core and PEO Shell as a Non‐spherical Carrier for Drug Delivery

Core/shell wormlike polymer brushes with densely grafted poly(ϵ‐caprolactone)‐b‐poly(ethylene oxide) (PCL‐b‐PEO) are synthesized via grafting an alkynyl terminated PCL‐b‐PEO (ay‐PCL₁₇‐b‐PEO₁₁₃) onto a well‐defined azido functionalized polymethacrylate (PGA₉₄₀) and are evaluated preliminarily as a single molecular cylindrical vehicle for drug delivery. Water soluble molecular worms of ca. 230 nm are obtained and then the anticancer drug doxorubicin (DOX) is loaded into its PCL core by hydrophobic interaction. Compared with spherical micelles from linear PCL₁₇‐b‐PEO₁₁₃, the brushes demonstrate a lower loading efficiency but a faster release rate of DOX. Confocal laser scanning microscopy measurements show that DOX‐loaded cylindrical molecular brushes can easily enter into HeLa and HepG2 cells in 1 h.     

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.     

Optimal Halbach permanent magnet designs for maximally pulling and pushing nanoparticles

Optimization methods are presented to design Halbach arrays to maximize the forces applied on magnetic nanoparticles at deep tissue locations. In magnetic drug targeting, where magnets are used to focus therapeutic nanoparticles to disease locations, the sharp fall off of magnetic fields and forces with distances from magnets has limited the depth of targeting. Creating stronger forces at a depth by optimally designed Halbach arrays would allow treatment of a wider class of patients, e.g. patients with deeper tumors. The presented optimization methods are based on semi-definite quadratic programming, yield provably globally optimal Halbach designs in 2 and 3-dimensions, for maximal pull or push magnetic forces (stronger pull forces can collect nanoparticles against blood forces in deeper vessels; push forces can be used to inject particles into precise locations, e.g. into the inner ear). These Halbach designs, here tested in simulations of Maxwell's equations, significantly outperform benchmark magnets of the same size and strength. For example, a 3-dimensional 36 element 2000 cm³ volume optimal Halbach design yields a 5× greater force at a 10 cm depth compared to a uniformly magnetized magnet of the same size and strength. The designed arrays should be feasible to construct, as they have a similar strength (≤1 T), size (≤2000 cm³), and number of elements (≤36) as previously demonstrated arrays, and retain good performance for reasonable manufacturing errors (element magnetization direction errors ≤5°), thus yielding practical designs to improve magnetic drug targeting treatment depths.     

Vascular permeability in cancer and infection as related to macromolecular drug delivery, with emphasis on the EPR effect for tumor-selective drug targeting

Tumor and inflammation have many common features. One hallmark of both is enhanced vascular permeability, which is mediated by various factors including bradykinin, nitric oxide (NO), peroxynitrite, prostaglandins etc. A unique characteristic of tumors, however, is defective vascular anatomy. The enhanced vascular permeability in tumors is also distinctive in that extravasated macromolecules are not readily cleared. We utilized the enhanced permeability and retention (EPR) effect of tumors for tumor selective delivery of macromolecular drugs. Consequently, such drugs, nanoparticles or lipid particles, when injected intravenously, selectively accumulate in tumor tissues and remain there for long periods. The EPR effect of tumor tissue is frequently inhomogeneous and the heterogeneity of the EPR effect may reduce the tumor delivery of macromolecular drugs. Therefore, we developed methods to augment the EPR effect without inducing adverse effects for instance raising the systemic blood pressure by infusing angiotensin II during arterial injection of SMANCS/Lipiodol. This method was validated in clinical setting. Further, benefits of utilization of NO-releasing agent such as nitroglycerin or angiotensin-converting enzyme (ACE) inhibitors were demonstrated. The EPR effect is thus now widely accepted as the most basic mechanism for tumor-selective targeting of macromolecular drugs, or so-called nanomedicine.