萘普生在新型缓释系统中的释药

亲水凝胶;萘普生;二醋酸纤维素;致孔剂;新型药物缓释系统     

中西药结合抗菌性甲壳胺复合膜的制备及其体外释放

利用甘油作为增塑剂，制备了以甲壳胺／淀粉／聚乙烯醇为基材的含有原儿茶酸（对烧伤、创伤有特效的中药）和环丙沙星（杀菌性能最强的抗菌剂）等的复合型生物敷料，研究了不同条件下制备的敷料膜其抗菌剂在林格试剂中的静态释放情况，并对释放机理进行了探讨．     

Ultrasound-Triggered Release of Ibuprofen from a Chitosan-Mesoporous Silica Composite- a Novel Approach for Controlled Drug Release

Summary: In this work, an attempt was made to synthesize a novel Chitosan-Mesoporous silica (CS-MS) hybrid composite to design a drug delivery system based on ultrasound triggered stimuli-responsive smart release. The in-vitro drug release properties of both the Mesoporous Silica (MS) and Chitosan (CS) hybrids were investigated. Ibuprofen (Ibu) was used as a model drug. The results from powder X-Ray diffraction (XRD) patterns, and BET N₂ adsorption isotherms exhibited that MS can accommodate drug molecules into the lumen of the channels and pores. Drug release, stimulated by temperature and pH of the release media was also investigated. We studied the Ultrasound (US) triggered release of Ibu in a simulated body fluid (pH 7.4). The results exhibited that US can be used as a non-invasive technique for drug release from polymeric materials. The enhancing effect of ultrasound on drug release is due to the Cavitation effect, without causing any significant destruction on the polymer morphology.     

甲壳胺-硅胶复合载体的制备及其在脂肪酶固定化中的应用

固定化脂肪酶;甲壳胺-硅胶复合载体的制备及其在脂肪酶固定化中的应用     

壳聚糖-g-聚甲基丙烯酸凝胶粒的制备及其药物释放行为

以壳聚糖和甲基丙烯酸为原料,硝酸铈铵为引发剂,合成了不同接枝率的壳聚糖-g-聚甲基丙烯酸(CS-g-PMAA),用FTIR、1H NMR和元素分析表征了产物的结构,以柠檬酸三钠和戊二醛为交联剂制备了具有核壳结构的CS-g-PMAA载药体系。 用UV/Vis检测了CS-g-PMAA粒子对模型药物的释放行为。 结果表明,CS-g-PMAA接枝率为12.21%时药物释放速率最慢,其在pH=1.8介质中药物累积释放量(11 h)为44.18%,而壳聚糖粒子的累积释放量高达65.24%,即接枝改性壳聚糖粒子对药物的缓慢控制释放性能较好; CS-g-PMAA粒子的释药行为还依赖于介质的pH值和盐浓度,在低pH值和低盐浓度下,药物释放速率较快;酶环境下由于载体材料的降解使药物释放速率加快。 分析了不同条件下CS-g-PMAA载药粒子中药物的释放机理。     

壳聚糖-聚丙烯酸复合水凝胶的药物控制释放行为

以壳聚糖(Cs)和丙烯酸(AA)为原料,利用自由基聚合法制备了具有孔洞结构的复合水凝胶Cs-PAA,并研究了AA的量、交联剂的量、聚合温度和AA的中和度对水凝胶溶胀度的影响以及复合水凝胶对烟酸的控制释放。 结果表明,Cs-PAA复合水凝胶具有良好的pH值、离子强度敏感性,且溶胀度最高达1228 g/g,其在pH=686的缓冲溶液中的烟酸累积释放率明显大于其在pH=1.80的缓冲溶液,因此Cs-PAA水凝胶可作为肠口服药物的载体。     

Chitosan‐Capped Mesoporous Silica Nanoparticles as pH‐Responsive Nanocarriers for Controlled Drug Release

Herein, we present a straightforward synthesis of pH‐responsive chitosan‐capped mesoporous silica nanoparticles (MSNs). These MCM‐41‐type MSNs could be used as nanocapsules to accommodate guest molecules. Subsequently, (3‐glycidyloxypropyl)trimethoxysilane was grafted onto the surface of the MSNs, which served as a bridge to link between MSNs and chitosan, which is ubiquitous in nature and commercially available. Owing to the pH‐responsive and biocompatible features of chitosan, the loading and release of an anti‐cancer drug, doxorubicin hydrochloride, were carried out in vitro, in which the composite chitosan‐capped MSNs (CS‐MSNs) showed excellent environmental response. As the pH value of the media decreased, the degree of drug release correspondingly increased. Moreover, thanks to the perfect biocompatibility of chitosan, the CS‐MSNs exhibited lower cytotoxicity than that of the naked MSNs in an MTT assay. In addition, the in vitro kill potency against MCF‐7 breast‐cancer cells was enhanced over time, as well as with increasing concentration of the drug‐loaded CS‐MSNs. These results indicate that CS‐MSNs are promising candidates for pH‐responsive drug delivery in cancer therapy.     

Organically Modified Sol‐Gel/Chitosan Composite Based Glucose Biosensor

A new type of organically modified sol‐gel/chitosan composite material was developed and used for the construction of glucose biosensor. This material provided good biocompatibility and the stabilizing microenvironment around the enzyme. Ferrocene was immobilized on the surface of glassy carbon electrode as a mediator. The characteristics of the biosensor were studied by cyclic voltammetry and chronoamperometry. The effects of enzyme‐loading, buffer pH, applied potential and several interferences on the response of the enzyme electrode were investigated. The simple and low‐cost glucose biosensor exhibited high sensitivity and good stability.     

Plasma Techniques for Preparation of Controlled Drug Release System

Plasma-induced surface radicals formed on a variety of organic polymers have been studied by electron spin resonance (ESR), making it possible to provide a sound basis for future experimental design of polymer surface processing, i.e., plasma treatment. On the basis of the findings from such studies, several pharmaceutical applications in the field of drug engineering have been devised, which include preparation of double-compressed tablets for reservoir-type drug delivery system (DDS) of sustained- and delayed-release, and fabrication of functionalized composite powders applicable for matrix-type DDS by a mechanical application of plasma-irradiated polymer powder.     

中酯化度果胶离子络合复合物凝胶对葡萄糖迁移的影响

通过控制中酯化度果胶多糖溶液pH、多价离子浓度以及对凝胶-溶胶温度曲线的测定,研究其凝胶敏感特性和可逆性能.利用中酯化度果胶多糖的凝胶特性,以体外模拟实验研究不同凝聚态多糖体系中葡萄糖的生成和迁移行为.结果表明:中酯化度果胶多糖具有酸敏感、多价离子敏感等凝胶特性,且其凝胶具有温度可逆性.在降低葡萄糖迁移速率和降低淀粉生成葡萄糖速率两方面,中酯化度果胶钙凝胶体系效果较其他体系明显,并且使生成葡萄糖呈均化释放.     

磁性壳聚糖微球的制备、表征及其靶向给药研究

磁性微球;阿司匹林;磁性壳聚糖微球的制备、表征及其靶向给药研究     

Formulation and Evaluation of Chitosan‐Gellan Based Methotrexate Implants

An implant controlled‐release system for methotrexate delivery based on a polyion complex composed of chitosan and gellan was investigated. Multi‐layered implant was prepared by using poly(vinyl alcohol), gellan and chitosan. Two chitosan layers sandwiched the poly(vinyl alcohol)‐gellan layer, which acted as a methotrexate reservoir. The prepared implant was evaluated for swellability, in vitro and in vivo release and biodegradation studies. The equilibrium swelling and methotrexate release was found to depend on a concentration of calcium chloride, which was used as a crosslinking agent for gellan. Drug‐loaded implants were subcutaneously implanted in the back of Wistar rats. The in vivo studies showed that methotrexate was released slowly for a period over 30 days and also there was no fibrous capsule formation around the implant indicating the biocompatibility of the implant.     

Composite Hydrogels for Sustained Release of Therapeutic Agents

The goal of this research is to develop a composite hydrogel system for sustained release of therapeutic agents. The hydrogel composites were prepared by embedding drug‐loaded, biodegradable poly (DL‐lactide‐co‐glycolide) (PLGA) microparticles in semicrystalline hydrogels of polyvinyl alcohol (PVA). The gels were physically cross‐linked by the formation of the crystallites. The presence of the crystallites and the composite nature of the structure were confirmed by using differential scanning calorimetry and ATR‐FTIR spectroscopy. The distribution of microparticles in the hydrogel matrix was evaluated by using confocal laser scanning microscopy with coumarin‐6 as a fluorescence marker. The numbers of particles in the hydrogel matrix increased along the scanning depth, indicating uneven distribution. The release behavior of a model therapeutic agent, hydrocortisone, was evaluated, and the hydrogel composite system provided for better control of release than the microparticles and hydrogels alone. The addition of outer layers of PVA to the original single‐layer composite further reduced the initial burst effect from the microparticles and allowed for a linear release profile for greater than 1 month.     

Well‐Defined Poly(Ortho Ester Amides) for Potential Drug Carriers: Probing the Effect of Extra‐ and Intracellular Drug Release on Chemotherapeutic Efficacy

To compare the chemotherapeutic efficacy determined by extra‐ and intracellular drug release strategies, poly(ortho ester amide)‐based drug carriers (POEAd‐C) with well‐defined main‐chain lengths, are successfully constructed by a facile method. POEAd‐C3‐doxorubicin (DOX) can be rapidly dissolved to release drug at tumoral extracellular pH (6.5–7.2), while POEAd‐C6‐DOX can rapidly release drug following gradual swelling at intracellular pH (5.0–6.0). In vitro cytotoxicity shows that POEAd‐C3‐DOX exhibits more toxic effect on tumor cells than POEAd‐C6‐DOX at extracellular pH, but POEAd‐C6‐DOX has stronger tumor penetration and inhibition in vitro and in vivo tumor models. So, POEAd‐C6‐DOX with the intracellular drug release strategy has stronger overall chemotherapeutic efficacy than POEAd‐C3‐DOX with extracellular drug release strategy. It is envisioned that these poly(ortho ester amides) can have great potential as drug carriers for efficient chemotherapy with further optimization.

     

Tramadol Release from a Delivery System Based on Alginate‐Chitosan Microcapsules

Alginate‐chitosan microcapsules to control the release of Tramadol‐HCl were prepared using two different methods. In the two‐stage procedure (Variant I) alginate was first pumped into a CaCl₂/NaCl solution and then transferred into a chitosan solution. In the one‐stage procedure (Variant II) alginate was directly pumped into a chitosan/CaCl₂ solution, and different behavior could be noted in each case. The microcapsules were spherical in both variants and they swelled to a greater extent in a basic medium as compared to an acid one. The drug release profile of Tramadol from microcapsules in simulated gastric fluid and simulated intestinal fluid was also studied. The maximum release of Tramadol at 24 h was 64% and 86% for Variant I and II, respectively, in simulated intestinal fluid. Release was adjusted using the power law of the semi‐empirical Peppas equation in order to gain information about the release mechanism. In both cases the values of the exponent were found to be between 0.53 and 0.84 for swellable microcapsules in simulated gastric and intestinal fluids, respectively, indicating anomalous drug transport for both variants. The good results obtained with alginate‐chitosan microcapsules are comparable to those of the best products so far described in the scientific bibliography and in addition, chitosan is useful in pharmacy.

Surface morphology of Tramadol‐loaded microcapsule.     

Green Algae as a Drug Delivery System for the Controlled Release of Antibiotics

New strategies to efficiently treat bacterial infections are crucial to circumvent the increase of resistant strains and to mitigate side effects during treatment. Skin and soft tissue infections represent one of the areas suffering the most from these resistant strains. We developed a new drug delivery system composed of the green algae, Chlamydomonas reinhardtii, which is generally recognized as safe, to target specifically skin diseases. A two-step functionalization strategy was used to chemically modify the algae with the antibiotic vancomycin. Chlamydomonas reinhardtii was found to mask vancomycin and the insertion of a photocleavable linker was used for the release of the antibiotic. This living drug carrier was evaluated in presence of Bacillus subtilis and, only upon UVA1-mediated release, growth inhibition of bacteria was observed. These results represent one of the first examples of a living organism used as a drug delivery system for the release of an antibiotic by UVA1-irradiation.     

Polysaccharide Nanoparticles Bearing HDAC Inhibitor as Nontoxic Nanocarrier for Drug Delivery

The histone deacetylase inhibitors (HDACi) are potent drugs in the treatment of inflammatory diseases and defined cancer types. However, major drawbacks of HDACi, such as valproic acid (VPA), are limited serum half‐life, side effects and the short circulation time. Thus, the immobilization of VPA in a polysaccharide matrix is used to circumvent these problems and to design a suitable nanocarrier system. Therefore, VPA is covalently attached to cellulose and dextran via esterification with degree of substitution (DS) values of up to 2.20. The resulting hydrophobic polymers are shaped to spherical nanoparticles (NPs) with hydrodynamic diameter between 138 to 221 nm and polydispersity indices from 0.064 to 0.094 by nanoprecipitation and emulsification technique. Lipase treatment of the NPs leads to in vitro release of VPA and hence to an inhibition of HDAC2 activity in a HDAC2 assay. NPs are rapidly taken up by HeLa cells and mainly localize in the cytoplasm. The NPs are hemocompatible and nontoxic as revealed by the shell‐less hen’s egg model.     

果胶改性硅胶复合材料的制备及其对亚甲基蓝的吸附性能

以废弃柚子皮中提取的果胶改性硅胶表面,制备出新型的果胶改性硅胶复合材料——P-硅胶,研究了P-硅胶对水中亚甲基蓝染料的吸附性能。利用红外光谱对材料进行表征,并通过分光光度法考察了用量、p H值、吸附时间、温度及实际水样对P-硅胶吸附亚甲基蓝性能的影响。硅胶经果胶改性后,其对亚甲基蓝的吸附容量由31.6 mg·g-1增至41.7 mg·g-1,吸附性能明显提高;P-硅胶对亚甲基蓝的吸附容量随着p H值、温度的升高而增大,碱性条件有利于吸附。结果显示:当p H 7.0,P-硅胶用量为5 mg,吸附时间为2 h,吸附温度为50℃时,制备出的P-硅胶对亚甲基蓝染料溶液的吸附容量最大可达59.2 mg·g-1。动力学研究显示,P-硅胶对亚甲基蓝的吸附能够在120 min内迅速达平衡,吸附行为符合准二级动力学方程,表明该吸附过程以化学吸附为主。吸附等温线研究表明,与Freundlich模型相比,实验数据拟合更符合Langmuir吸附等温模型。P-硅胶对环境水样中亚甲基蓝的去除率可达90%以上。     

Drug Encapsulation and Release by Mesoporous Silica Nanoparticles: The Effect of Surface Functional Groups

Mesoporous silica nanoparticles (MSNPs) have been widely used as drug carriers for stimuli‐responsive drug delivery. Herein, a catalysis screening technique was adopted for analyzing the effects of chain length, terminal group, and density of disulfide‐appended functional ligands on the surface of MSNPs on drug‐loading capacity and glutathione‐triggered drug‐release kinetics. The ligand with an intermediate length (5 carbon atoms) and a bulky terminal group (cyclohexyl) that complexes with theβ‐cyclodextrin ring showed the highest drug loading capacity as well as good release kinetics. In addition, decreasing the surface coverage of the functional ligands led to an enhancement in drug release. In vitro drug‐delivery experiments on a melanoma cell line (B16‐F10) by using the functionalized MSNPs further supported the conclusion. The results obtained may serve as a general guide for developing more effective MSNP systems for drug delivery.     

Crosslinked Networks Based on Polysaccharides and Collagen for Pilocarpine Sustained Release

The paper presents the experimental studies regarding synthesis and characterization of hydrogels based on gellan (Gel)/chitosan (CS) and collagen (Col), obtained by crosslinking with glutaraldehyde (GLA). The influence of the polysaccharide content and GLA ratio on the final composition and swelling characteristics was evaluated. Hydrogels swelling analysis, in distilled water and phosphate buffer (PBS, pH 7.2) has shown higher swelling degrees at increased concentration of polysaccharide into hydrogels. In vitro release of pilocarpine has demonstrated the possibility to use gellan-collagen and chitosan-collagen hydrogels as ophthalmic drug delivery matrix.