布洛芬在阴离子交换树脂上的负载及其缓释

将布洛芬通过静电和疏水作用的共同作用负载于聚苯乙烯型大孔弱碱性阴离子交换树脂D301R和D301T上,最佳负载条件为:布洛芬悬浮于5~10%的乙醇水溶液中,加入树脂后在60℃下搅拌12h,负载量可达到0.49g/g树脂。研究了负载的布洛芬在模拟胃肠道的条件下(pH2下2h、pH 7.4下4h和pH 6.7下18h)的释放动力学,在前12h的释放接近于线性释放,释放率为58~60%。后12h的释放量较小,释放率为13~17%。如果每12h服药1次,第2次服药后的24h的累加释放率接近于线性释放。与聚苯乙烯骨架的大孔弱碱性阴离子交换树脂相比,聚甲基丙烯酸酯骨架的弱碱性阴离子交换树脂(甲基丙烯酸正丁酯/甲基丙烯酸N,N-二甲胺基乙酯/双甲基丙烯酸乙二醇酯共聚物)负载的布洛芬在相同释放条件下突释明显,表明布洛芬与苯乙烯型弱碱性阴离子交换树脂之间的π-π作用在布洛芬的缓释中起关键的作用。     

Preparation,Characterization of Hydrophobic Drug in Combine Loaded Chitosan/Cyclodextrin/Trisodium Citrate Nanoparticles and in vitro Release Study

Chitosan/cyclodextrin/trisodium citrate(CS/CD/TSC) nanoparticles with ibuprofen(IBU) loaded were prepared via the ionic cross-linking method, with trisodium citrate selected as the cross-linking agent. The drug-loading capacity, particle size, zeta potential and surface morphology of the obtained nanoparticles were investigated. The results show a good drug-loading capacity. The prepared nanoparticles were spherical in shape with an average size of 293.7 nm and a zeta potential of +30.72 mV. The in vitro release studies show that the controlled release of IBU from the nanoparticles was followed. The drug release from CS/β-CD/TSC nanoparticles followed non-Fickian or anomalous diffusion.     

增塑剂对可吸收缝合线后处理工艺条件和降解性能的影响

分别在对二氧环己酮均聚物和对二氧环己酮-乙交酯共聚物中加入增塑剂进行纺丝,制得聚对二氧环己酮单丝缝合线(PDS)和对二氧环己酮-乙交酯共聚物单丝缝合线(PDG).用DSC方法研究了增塑剂含量对PDS缝合线热性能的影响和不同热定型条件的PDG缝合线的热性能,测试了热定型温度对PDG缝合线初始强度、模量及柔量的影响,考察了增塑剂含量对两种缝合线的生物降解性能和力学降解性能影响.研究结果表明,PDS缝合线的玻璃化转变温度Tg、结晶温度Tc以及熔融温度Tm均随着增塑剂含量的增加而降低,但其结晶能力增加.随着热定型温度的增加,PDG缝合线的初始打结强度、熔融热均提高,熔融温度Tm基本保持不变.两种缝合线的强度保留率随着增塑剂含量的增加均先增加后减小,而重量保留率随着增塑剂含量增加始终减小.     

Smart nanocontainers as depot media for feedback active coatings

Among the grand challenges at present are ways to develop systems with low consumption of raw materials and with little load on the environment. In view of this it is of utmost importance to avoid or to delay processes causing material destruction. This is especially urgent, since many protective substances have associated health hazards, and new routes to improve the situation are a main concern of this contribution. Nanocapsules (nanocontainers) with controlled release properties of the shell can be used to fabricate a new family of active coatings, with quick response to changes of the coating environment or coating integrity. The release of active materials encapsulated into nanocapsules is triggered by various external and internal factors, thus preventing spontaneous leakage of the active component. The coating can have several active functionalities when several types of nanocapsules loaded with corresponding active agent are incorporated simultaneously into a coating matrix. We highlight recent achievements in development and application of filled responsive containers in biomedical and self-healing protective coatings.     

Self-assembly of human serum albumin (HSA) and L-alpha-dimyristoylphosphatidic acid (DMPA) microcapsules for controlled drug release

Human serum albumin (HSA) and L-alpha-dimyristoylphosphatidic acid (DMPA) were applied as a pair to encapsulate ibuprofen microcrystals by means of a technique based on the layer-by-layer (LbL) assembly of oppositely charged species, for the purpose of controlling drug release. The successful adsorption of HSA and DMPA multilayers onto ibuprofen crystals was confirmed by optical microscopy. The drug release process, in a solution of pH 7.4, was monitored by optical microscopy and UV spectroscopy. The results revealed that the rate of release of ibuprofen from HSA/DMPA microcapsules decreased as the capsule wall thickness and drug crystal size increased, indicating that the permeability of the microcapsules can be controlled by simply varying the number of HSA/DMPA deposition cycles.     

5-氟尿嘧啶在pH敏感型分子筛控释载体中的缓释行为

以肠溶性的羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)作为包覆材料,制备了HPMCP包覆的SBA-15介孔分子筛药物控释载体(HPMCP/SBA-15),并考察了抗癌药物5-氟尿嘧啶(5-Fu)负载于控释载体后,在不同pH释放环境中的释放行为.结果表明,在模拟胃液中(pH=1.2),HPMCP能明显地延缓5-Fu的释放速度;药物释放4h后,其释放率仅为15%.而在模拟肠液中(pH=7.5)HPMCP迅速溶解,对5-Fu释放速度的影响甚微;药物释放4h后,释放率可达到80%.与此同时,包覆膜的干燥温度影响5-Fu的释放行为,干燥温度越高,药物在模拟胃液中的释放速度越慢.     

Chitosan nanoparticle as protein delivery carrier--systematic examination of fabrication conditions for efficient loading and release

Chitosan nanoparticles fabricated via different preparation protocols have been in recent years widely studied as carriers for therapeutic proteins and genes with varying degree of effectiveness and drawbacks. This work seeks to further explore the polyionic coacervation fabrication process, and associated processing conditions under which protein encapsulation and subsequent release can be systematically and predictably manipulated so as to obtain desired effectiveness. BSA was used as a model protein which was encapsulated by either incorporation or incubation method, using the polyanion tripolyphosphate (TPP) as the coacervation crosslink agent to form chitosan-BSA-TPP nanoparticles. The BSA-loaded chitosan-TPP nanoparticles were characterized for particle size, morphology, zeta potential, BSA encapsulation efficiency, and subsequent release kinetics, which were found predominantly dependent on the factors of chitosan molecular weight, chitosan concentration, BSA loading concentration, and chitosan/TPP mass ratio. The BSA loaded nanoparticles prepared under varying conditions were in the size range of 200-580nm, and exhibit a high positive zeta potential. Detailed sequential time frame TEM imaging of morphological change of the BSA loaded particles showed a swelling and particle degradation process. Initial burst released due to surface protein desorption and diffusion from sublayers did not relate directly to change of particle size and shape, which was eminently apparent only after 6h. It is also notable that later stage particle degradation and disintegration did not yield a substantial follow-on release, as the remaining protein molecules, with adaptable 3-D conformation, could be tightly bound and entangled with the cationic chitosan chains. In general, this study demonstrated that the polyionic coacervation process for fabricating protein loaded chitosan nanoparticles offers simple preparation conditions and a clear processing window for manipulation of physiochemical properties of the nanoparticles (e.g., size and surface charge), which can be conditioned to exert control over protein encapsulation efficiency and subsequent release profile. The weakness of the chitosan nanoparticle system lies typically with difficulties in controlling initial burst effect in releasing large quantities of protein molecules.     

Synthesis of polyaniline‐modified mesoporous‐silica containers for anticorrosion coatings via in‐situ polymerization and surface‐protected etching

An efficient type of container for anticorrosion coating based on polyaniline (PANI) modified mesoporous silica (pS) sphere has been first prepared via in‐situ polymerization and surface‐protected etching. The PANI‐modified containers not only show higher concentration of loaded inhibitor than pS, but also protect steel well because of the PANI. The coating with 1H‐benzotriazole (BTA) loaded containers shows significant anticorrosion property because of the release of BTA from containers. The structure and morphology of container are characterized by FTIR, XRD, SEM and TEM. The release of BTA from pS and PANI‐modified containers is determined by UV in water. The possible self‐healing anticorrosion performances are evaluated by EIS and polarization curves which indicate that the coating including BTA‐loaded containers performs best. The strategy of modifying pS by PANI is effective and successful. Copyright © 2016 John Wiley & Sons, Ltd.     

Hydrogel matrices containing single and mixed natural cyclodextrins. Mechanisms of drug release

Hydrogel networks of α, β or γ-cyclodextrin (CD) and mixtures of α/β or β/γ CDs have been obtained using epichlorohydrin (EP) as a crosslinking agent. Discs of the resulting polymers were evaluated as drug carriers for controlled release using the antiinflammatory naproxen (NAP) as a model drug. βCD polymer (βCDP) has shown the highest amount of drug loaded and the lowest one corresponds to the polymer containing αCD, in agreement with the affinities of NAP for the corresponding cyclodextrins.     

Drug Release and In Vitro Assays of Bioactive Polymer/Glass Mixtures

The bioactive behaviour and drug release of samples composed by sol gel glass with composition 80SiO₂-16CaO₂-4P₂O₅% mol, polymethylmethacrylate (PMMA) and gentamicine or ibuprofen have been studied. The bioactive behaviour of the samples does not depend on the amount (5% and 10% in weight) or on the type of drug used in this study. In all the cases the SEM micrographs show the formation of a layer that covers the surface of the samples after 24 hours soaked in simulated body fluid (SBF). X ray diffraction patterns show two broad peaks after being soaked 3 days. These peaks could be identified with an apatite-like phase, characteristic in this kind of studies.On the contrary, the release kinetics is strongly dependent on the drug employed. In the case of gentamicine, the curve shows a high slope during the first day soaked in SBF and the complete release occurs before 150 hours. For the ibuprofen samples, the drug release is much slower; the samples containing 10% of ibuprofen do not reach the total release after 600 hours. This different behaviour could be related with the solubility of both drugs in aqueous media.     

Temperature sensitive poly[N-isopropylacrylamide-co-(acryloyl beta-cyclodextrin)] for improved drug release

The model drugs ibuprofen (IBU) and tegafur (T-Fu) were loaded into poly[N-isopropylacrylamide-co-(acryloyl beta-cyclodextrin)] [P(NIPA-co-A-CD)] and PNIPA hydrogels by immersing dried gels in IBU or T-Fu alcohol solutions until they reached equilibrium. Drug release studies were carried out in water at 25 degrees C. In contrast to the release time of conventional PNIPA hydrogel, that of IBU from the beta-CD incorporated hydrogel was significantly prolonged and the drug loading was also greatly increased, which may be the result of the formation of inclusion complexes between CD and ibuprofen. However, another hydrophilic drug, tegafur, did not display these properties because it could not form a complex with the CD groups. [diagram in text].     

Effects of Morphology and Structural Characteristics of Ordered SBA-15 Mesoporous Silica on Release of Ibuprofen

Three kinds of highly ordered SBA-15 mesoporous materials with different pore sizes and morphologies denoted as LPS-SBA-15 (stick-like with pore size 7.28 nm), CPS-SBA-15 (stick-like with pore size 5.96 nm) and T-SBA-15 (tablet-like with pore size 4.64 nm) have been prepared, characterized and employed as carrier materials. The release behaviors of the ibuprofen in a simulated body fluid from these mesoporous silica materials were studied. The influences of pore size and exterior morphologies of mesoporous silica on the release behaviors of ibuprofen have been investigated. It has been found that the release becomes fast with increasing of pore size and slow with extending of transport pathway, and that the release rate of ibuprofen from the three kinds of SBA-15 is LPS-SBA-15 > T-SBA-15 > CPS-SBA-15. The results show that the inner structure as well as the exterior morphologies of SBA-15 mesoporous silica can seriously affect the release behaviors of ibuprofen.     

Dynamical Mechanical Analysis and Curing Analysis of Fouling Release Coatings and Components

A commercially available fouling release (adsorbed foulants removed by shear flow) coating based on poly(dimethylsiloxane) and a commercial marine epoxy primer have been analyzed by diffusing wave spectroscopy and by thermal and dynamical mechanical methods. Diffusing wave spectroscopy reveals 7–9 distinct relaxation intervals over short (minutes) to long (20 hour) time scales. Several junctures of these intervals are shown to correlate with mechanically determined film formation parameters, such as set to touch times, tack free times, and dry through times. Thickness series of coatings made by casting illustrate similarities and distinct differences between the epoxy primer and poly(dimethylsiloxane)-based fouling release coating formulations. Several low temperature β transitions are resolved in the fouling release coatings in addition the α (T_g) transition in both formulations. A scaling analysis of the thickness series data shows that both the primer and the top coat exhibit a negative exponent for thickness; −0.77 for the epoxy; −1.2 for the top coat. Stress-strain experiments reveal further significant difference between these two types of elastomers. The elastic modulus for the epoxy is 1000-fold higher than for the topcoat. A small elastic modulus is thought to be key in the successful functioning of fouling release coatings. Analyses of substrate effects (wire mesh, fiberglass braid) and of coating or loading levels on dynamical mechanical properties, in comparison with thickness series of thin films are presented. The woven braid offers the advantage that it can be loaded more easily than can wire mesh substrates. The negative exponents show that thinner coatings may be more mechanically resilient than thicker coatings, as the ability to store and dissipate mechanical energy decreases as thickness increases.     

High-throughput study of poly(ethylene glycol)/ibuprofen formulations under controlled environment using FTIR imaging

Simultaneous analysis of many samples under identical conditions improves the effectiveness of research and accelerates product design. A novel spectroscopic imaging approach using a multichannel detector has been developed for parallel analysis of pharmaceutical formulations under controlled environments. Samples of formulations of ibuprofen in poly(ethylene glycol) have been prepared with ibuprofen concentrations ranging from 0 to 100% using a microdroplet deposition approach. The concentration of ibuprofen in PEG at which dimerization of ibuprofen molecules can be avoided has been determined via simultaneous measurement of all samples using in situ FTIR spectroscopic imaging. FTIR spectra from all samples have been analyzed to assess the molecular state of the drug and the degree of polymer swelling as a function of drug concentration. The effect of elevated temperature on the stability of all formulations was also studied. This high-throughput approach identified the concentration range for stable formulations and provided evidence that hydrogen bonding between ibuprofen and the polymer is responsible for enhanced stability at higher temperatures. This high-throughput imaging approach, based on a miniature sampling system, significantly reduces the experimental time by allowing many (potentially a few thousand) experiments to be run in parallel and increases the accuracy by minimizing variations between experiments.     

Influence of mesoporous structure type on the controlled delivery of drugs: release of ibuprofen from MCM-48, SBA-15 and functionalized SBA-15

Ordered mesoporous materials exhibit potential features to be used as controlled drug delivery systems, including their wide range of chemical compositions and their outstanding textural and structural properties. Therefore, it is possible to control the drug release kinetics by tailoring such parameters. In this paper, mesoporous materials such as MCM-48 and SBA-15, which present different pore sizes (3.7 and 8.8 nm) and structural characteristics (3D-bicontinuous cubic and 2D-hexagonal, respectively) have been synthesized to evaluate their application as drug delivery system and to determine their influence on release kinetic of ibuprofen. Moreover, a chemical modification of the SBA-15 mesoporous material with octadecyltrimethoxysilane has also been performed to study its influence on the release rate of ibuprofen. The structural characteristics (3D cubic and 2D hexagonal pore system) do not affect the release kinetic profiles of ibuprofen. On the contrary, the pore size affects highly to the release kinetic profiles from first-order kinetic to zero-order kinetic for MCM-48 and SBA-15, respectively. Moreover, the importance of surface functionalization was demonstrate through the very fast delivery of ibuprofen from SBA-15 mesoporous materials functionalized with octadecyl chains.     

层状复合氢氧化物对乙酰苯甲酸的负载与体外释放

共沉淀-微波晶化法合成层状复合氢氧化物(LDH)后, 用不同方式将乙酰苯甲酸(ASP)组装到LDH层间制成载药体LDH-ASP, 通过对合成及药物释放前后的液相分析与固相表征数据研究了LDH对ASP的负载及载药体LDH-ASP在磷酸盐介质的溶释现象. 结果表明: LDH层间通道是负载、贮存及控制药物释放的微观基础; 载体选择、药物配比、反应能量供给方式及搅拌强度是决定并影响LDH-ASP载药效率的基本因素, LDH-ASP结构参数可以反映药物负载情况、并与其释放性能明确相关; LDH对ASP的负载与释放均致晶胞参数改变、结晶度下降; 载药体与前体的晶态属性、热力学行为及表面特性相似, 而释放药物后固相的晶态性征减弱、无定形性增强、通道吸附活性降低, 有利于使命后载体在体内降解消除.     

Antimicrobial Surgical Sutures: Recent Developments and Strategies

Surgical sutures are probably the most widely used medical devices in healthcare applications for wound closure. During their application, sutures may be exposed to microorganisms present in the environment leading to bacterial biofilm formation, and thereon to surgical site infections. The physicochemical characteristics of the polymeric substrate play a major role in directing the behavior of the suture in a biological milieu. In such a context, it is necessary to develop sutures which actively repel and inhibit bacterial adherence and colonization on their surfaces. Drug eluting sutures have been proposed as a solution to this dilemma. Currently, bioactive agents (natural or synthetic) are being incorporated in polymeric materials via various methods including blending and compounding, surface functionalization and conjugation, and coating to render antimicrobial surgical sutures. However, each of these methods has its own pros and cons. Depending upon the nature of the substrate, an appropriate processing technique has to be chosen. In this article, we review the recent state-of-the-art developments and strategies in antimicrobial surgical suture fabrication. The efficacy and mechanism of these sutures in controlling infection is critically analyzed. However, such bioactive agent incorporated sutures have to be tested in clinically randomized trials to accurately gauze their applicability in a surgical setting. Presently, very few antimicrobial surgical sutures are available commercially. Therefore, there is a great scope for market development in this area.     

In-line prediction of drug release profiles for pH-sensitive coated pellets

A new method for the prediction of the drug release profiles during a running pellet coating process from in-line near infrared (NIR) measurements has been developed. The NIR spectra were acquired during a manufacturing process through an immersion probe. These spectra reflect the coating thickness that is inherently connected with the drug release. Pellets sampled at nine process time points from thirteen designed laboratory-scale coating batches were subjected to the dissolution testing. In the case of the pH-sensitive Acryl-EZE coating the drug release kinetics for the acidic medium has a sigmoid form with a pronounced induction period that tends to grow along with the coating thickness. In this work the autocatalytic model adopted from the chemical kinetics has been successfully applied to describe the drug release. A generalized interpretation of the kinetic constants in terms of the process and product parameters has been suggested. A combination of the kinetic model with the multivariate Partial Least Squares (PLS) regression enabled prediction of the release profiles from the process NIR data. The method can be used to monitor the final pellet quality in the course of a coating process.     

RELEASE OF IBUPROFEN FROM PEG-PLLA ELECTROSPUN FIBERS CONTAINING POLY(ETHYLENE GLYCOL)-b-POLY(α-HYDROXY OCTANOIC ACID) AS AN ADDITIVE

<正>Poly(α-hydroxy octanoic acid) was first used as an additive for the preparation of electrospun ultra-fine fibers of poly(ethylene glycol)-b-poly(L-lactide)(PEG-PLLA).Ibuprofen was loaded in the electrospun ultra-fine fibers.The results from environmental scanning electron microscopy(ESEM),wide angle X-ray diffraction(WAXD) and differential scanning calorimetry(DSC) demonstrated that ibuprofen could be perfectly entrapped in the fibers electrospun from PEG-PLLA usingα-hydroxy octanoic acid or PEG-b-poly(α-hydroxy octanoic acid)(PEG-PHOA) as additives.Compared with electrospun PEG-PLLA fibers which entrapped 20 wt%ibuprofen,the PEG-PLLA electrospun fibers containing PEG-PHOA exhibited integral and robust after 1 week incubated in 37℃,pH 7.4 phosphate buffer solution with 10μg/mL proteinase K.Compared with electrospun fibers without PEG-PHOA,the concentration of proteinase K in release media had less effect on the release rate of ibuprofen.An unique release profile was found from PEG-PLLA fiber after the incorporation of PEG-PHOA. Enzyme degradation experiments demonstrated that PEG-PHOA but notα-hydroxy octanoic acid monomer was the crucial factor for integrity maintenance of the electrospun fibers,which may be due to the enzyme degradation tolerance property of the PEG-PHOA polymer additive.     

Calcium Phosphate Nanocarriers Dual‐Loaded with Bovine Serum Albumin and Ibuprofen: Facile Synthesis,Sequential Drug Loading and Sustained Drug Release

A simple and green strategy is reported for the preparation, drug loading, and release properties of a drug delivery system consisting of calcium phosphate (CP) nanocarriers dual‐loaded with bovine serum albumin (BSA) and hydrophobic drug ibuprofen (IBU). The sequential loading of BSA and IBU in calcium phosphate nanocarriers and in vitro simultaneous release of BSA and IBU are realized and investigated. In this method, BSA, which is used as a model protein drug, is encapsulated in situ in calcium phosphate nanocarriers. Subsequently, the typical hydrophobic drug IBU is loaded in the BSA/CP drug delivery system, forming the IBU/BSA/CP dual drug delivery system. The experiments reveal that the preloaded BSA not only reduces the cytotoxicity of calcium phosphate nanocarriers but also significantly improves the IBU drug loading capacity in calcium phosphate nanocarriers and greatly extends the duration of drug release. Thus, the as‐prepared IBU/BSA/CP dual drug delivery system is promising for drug delivery applications.