Nanostructured Lipid Carriers (NLC)-Based Gel Formulations as Etodolac Delivery: From Gel Preparation to Permeation Study

Topical administration of drug is an attractive alternative to the oral administration as it provides a reduction in adverse reactions and an enhancement of therapeutic effects. The use of lipid carriers in hydrogel structures makes it possible to introduce lipophilic substances in a dissolved form. In this study, an NSAID from the BCS class II, etodolac (ETD), was used. The nanostructured lipid carriers (NLC) obtained with ETD were incorporated into semi-solid forms (gels). Hydrogels with the suspended drug and oleogel were also prepared for comparison purposes. The obtained gels were tested in terms of pH, viscosity, rheological, mechanical, and bioadhesive properties. The release and permeation through membranes were also studied. All tested formulations were characterized by a pH below 7, which ensured the physiological state of the skin. The viscosities of all gels decreased with increasing shear rate, indicating non-Newtonian behavior. The fastest ETD release was observed for NLC with a Carbopol base (formulation F1); a similar result was noticed in the permeation test. The developed gel formulations containing ETD-NLC dispersion and Carbopol or Poloxamer as gelling agents were stable and possessed beneficial pharmaceutical properties.     

类脂立方液晶作为药物载体的研究

综述了近年来类脂立方液晶作为药物载体的研究进展,特别是对甘油单油酸酯/水体系形成的立方液晶进行了详细的介绍和讨论;重点论述了类脂立方液晶的物理化学性质以及类脂立方液晶作为药物载体的特点和药物对相态的影响;同时还探讨了类脂立方液晶作为药物载体的应用前景.     

水滑石型磁性纳米载药粒子的制备及其体外药物释放性能研究

通过调变镁铁尖晶石的含量, 采用一步共沉淀法制备了一系列具有核壳结构的水滑石型磁性纳米载药粒子, 对其微结构、热稳定性、磁性和药物释放性能进行了系统的研究. 结果表明这种磁性纳米载药粒子是一种具有以镁铁尖晶石为核层、双氯酚酸(Diclofenac, DIC)插层水滑石(DIC-LDH)为壳层的复合纳米粒子, 粒径在90～180 nm之间. 其中壳层DIC-LDH的晶粒尺寸D₁₁₀和层板电荷密度随磁核含量的增大而逐渐减小. 磁性纳米载药粒子的载药量随磁核含量的增大而逐渐减小, 而其比饱和磁化强度则随着磁核含量的增大逐渐增大. 体外释放实验表明, 无外加磁场时, 磁核含量增大, 壳层DIC-LDH粒径减小, 磁性纳米载药粒子药物释放速率逐渐增大|外加1500 G磁场时, 磁核含量增大, 磁致团聚程度增大, 其药物释放速率逐渐减小.     

Controlling Liquid Crystal Configuration and Phase Using Multiple Molecular Triggers

Liquid crystals are able to transform a local molecular interaction into a macroscopic change of state, making them a valuable “smart” material. Here, we investigate a novel polymeric amphiphile as a candidate for molecular triggering of liquid crystal droplets in aqueous background. Using microscopy equipped with crossed polarizers and optical tweezers, we find that the monomeric amphiphile is able to trigger both a fast phase change and then a subsequent transition from nematic to isotropic. We next include sodium dodecyl sulfate (SDS), a standard surfactant, with the novel amphiphilic molecules to test phase transitioning when both were present. As seen previously, we find that the activity of SDS at the surface can result in configuration changes with hysteresis. We find that the presence of the polymeric amphiphile reverses the hysteresis previously observed during such transitions. This work demonstrates a variety of phase and configuration changes of liquid crystals that can be controlled by multiple exogenous chemical triggers.     

Sol-Gel Carrier Systems for Controlled Drug Delivery

Embedding of the well-known coronary therapeuticum nifedipine into a modified silica matrix by the sol-gel technique allows its releasing behavior to be controlled to a high degree. The liberation rate is proportional to temperature and is increased by the addition of penetration agents such as sorbitol, but is inversely proportional to particle size and is decreased by modification of the silica matrix with methyl-triethoxysilane or polyethylene-glycol. It is presumed that the drug is dispersed in the gel matrix and that diffusion occurs through solvent-filled capillary channels. The liberation rate is governed by the relationship between the rates of dissolution and diffusion.     

多功能脂质体递药系统

脂质体是第一种成功进入临床应用,也是目前进入临床应用最多的一类纳米递药体系,将药物装载于脂质体中可以实现降低非特异性吸收、提高靶组织的富集量、降低副作用等目的。但是当前的脂质体技术仍然存在着诸多缺陷,例如载药量低以及靶向效果差等。新的脂质体载药技术的发展使得脂质体的载药量和包封率有了很大的提升。将热、激光、超声、离子辐射等外源物理刺激与脂质体药物结合可以提高脂质体药物在肿瘤的富集量,同时调节药物的释放。脂质体独特的核壳结构使得脂质体可以同时装载多种药物从而实现联合给药,通过合理设计脂质体纳米材料的结构不仅能够实现多种药物的递送,还能够实现药物的程序性释放。脂质体不仅能够装载治疗性药物,还能装载具有造影功能的组分,从而实现对治疗过程的影像监控。本文将主要介绍近五年在脂质体的载药方法、靶向给药、药物控释、联合给药、影像可视化等方面的一些重要进展。     

新型仿生聚合物胶束用于纳米药物载体的研究

对两亲性聚合物进行设计和优化, 从细胞膜仿生的设计出发, 利用原子转移自由基聚合, 制备了一种以胆固醇为疏水段、以仿细胞膜磷酸胆碱基聚合物为亲水段的两亲性分子CMPC. 在对其溶液胶束自组装行为进行探索的基础上, 以水包油(O/W)溶剂挥发法制备了包含抗癌药物阿霉素(ADR)的纳米抗癌药物载体, 通过体外细胞培养, 研究了仿细胞膜两亲分子的细胞相容性, 并对抗癌纳米药物载体抗肿瘤细胞的药效进行了初步研究.     

Determination of Tandospirone and its Impurities in Drug Formulations by LC-UV and LC-MS

This work describes the determination of tandospirone in bulk drug substance and formulated products by a reversed-phase liquid chromatographic method with UV detection. Chromatographic separation was performed on a C₁₈ column with a mobile phase of a binary mixture of methanol and water (70:30, v/v) delivered at a flow rate of 0.5 mL min^–1 and detection was performed at 243 nm. The proposed LC method is selective, precise and accurate for the determination of tandospirone in the presence of its manufacturing impurities with a limit of quantitation of 0.54 g mL^–1. A preliminary study for the identification of the major manufacturing impurities was made by liquid chromatography-mass spectrometry with electrospray ionization source operated in a positive ion mode.     

Minimum Evaporation Model of Dermatological Delivery Systems. Lamellar Liquid Crystal Formulations Containing Brazilian Nut (Bertholletia excelsa HBK) Vegetable Oil and Guarana Glycolic Extract

Formulations with lyotropic liquid crystals were prepared from a Brazilian nut vegetable oil, guarana extract and combination of sorbitan monooleate (Span 80) and sorbitan monolaurate ethoxylate EO 20 (Tween 20) in the ratio 1:3 (surfactant component) and their physical–chemical aspects and rheological properties were determined. Compositions with liquid crystals were found in the pseudoternary diagram in a surfactant range of 70–90% and polarized light microscopy, small-angle x-ray scattering (SAXS) showed them to be lamellar. The preparations were furthermore characterized rheologically by shear stress shear rate sweeps finding plastic and pseudoplastic behavior without thixotropy. Electric conductivity and pH measurements demonstrated a potential for future application as dermatological delivery system of the active compounds in the Bertholletia excelsa and Paullinia cupana.      

天然高分子药物微球载体材料的研究进展

综述了国内外在天然高分子药物微球载体材料研究及应用中的进展状况,主要从天然高分子药物微球载体材料的分类、微球的制备方法及特点、载药微球的给药途径和应用等进行概括,并对目前所存在的问题进行了描述。     

pH敏感型mPEG-Hz-PLA聚合物纳米载药胶束的制备

以合成的含有腙键的聚乙二醇大分子(mPEG-Hz-OH)为引发剂,以丙交酯为单体引发开环聚合反应,并通过调整投料比,制备出3种不同分子量的含腙键的生物可降解嵌段聚合物(mPEG-Hz-PLA).将腙键引入到聚合物的骨架中,以此构建聚合物胶束并作为pH敏感型纳米药物载体.制备的pH敏感型胶束的CMC值等于或低于5.46×10-4 mg/m L,DLS和TEM显示粒径均小于100 nm,且粒径分布均匀.非pH敏感型胶束在不同pH下的粒径变化不明显,而pH敏感型胶束在酸性环境下(pH=4.0和pH=5.0)胶束粒径出现了明显变化.以阿霉素为模型药物制备了pH敏感型载药胶束,其粒径比空白胶束大(100~200 nm),且粒径分布均匀.药物释放实验表明pH敏感型载药胶束随着释放介质pH降低累积释药量增高.MTT实验表明空白胶束对HeLa细胞和RAW264.7细胞几乎没有抑制作用,而载阿霉素的胶束对2种细胞的抑制作用都随着剂量的增大和时间的延长而增强.     

高分子包囊药物释放体系

用高分子作为载体的高分子微包囊和纳米级包囊药物制剂不仅能控制药物以一定的速度释放，而且可对生物体的生理指标变化作出反馈，因而可以成为靶向药物释放体系。通过用高分子包囊还可以延长蛋白质和多肽类药物的生理活性，提高药物稳定性，使之成为长效药物，并使一些难以口服的药物能够制成口服制剂。文章在介绍有关高分子药物释放体系的一些基本原理，以及与之相关的药学、药理学、物理化学和高分子材料科学方面知识的基础上，较全面地综述了高分子包囊药物的制备技术和应用。阐述了高分子包囊的粒径、表面积、孔度、药物性能和药含量，以及高分子包囊材料的性能对药物释放行为的影响。对药物传送机理亦进行了扼要的介绍。     

Soft Contact Lenses as Drug Delivery Systems: A Review

This review describes the role of contact lenses as an innovative drug delivery system in treating eye diseases. Current ophthalmic drug delivery systems are inadequate, particularly eye drops, which allow about 95% of the active substance to be lost through tear drainage. According to the literature, many interdisciplinary studies have been carried out on the ability of contact lenses to increase the penetration of topical therapeutic agents. Contact lenses limit drug loss by releasing the medicine into two layers of tears on either side of the contact lens, eventually extending the time of contact with the ocular surface. Thanks to weighted soft contact lenses, a continuous release of the drug over an extended period is possible. This article reviewed the various techniques to deliver medications through contact lenses, examining their advantages and disadvantages. In addition, the potential of drug delivery systems based on contact lenses has been extensively studied.     

Next Generation Multiresponsive Nanocarriers for Targeted Drug Delivery to Cancer Cells

C?H bond activation of 2‐methoxyethylamino‐bis(phenolate)‐yttrium catalysts allowed the synthesis of BAB block copolymers comprised of 2‐vinylpyridine (2VP; monomer A) and diethylvinylphosphonate (DEVP; monomer B) as the A and B blocks, respectively, by rare‐earth‐metal‐mediated group‐transfer polymerization (REM‐GTP). The inherent multi‐stimuli‐responsive character and drug‐loading and ‐release capabilities were observed to be dependent on the chain length and monomer ratios. Cytotoxicity assays revealed the biocompatibility and nontoxic nature of the obtained micelles toward ovarian cancer (HeLa) cells. The BAB block copolymers effectively encapsulated, transported, and released doxorubicin (DOX) within HeLa cells. REM‐GTP enables access to previously unattainable vinylphosphonate copolymer structures, and thereby unlocks their full potential as nanocarriers for stimuli‐responsive drug delivery in HeLa cells. The self‐evident consequence is the application of these new micelles as potent drug‐delivery vehicles with reduced side effects in future cancer therapies.     

Versatile Pectin Grafted Poly (N-isopropylacrylamide); Modulated Targeted Drug Release

This study describes synthesis and optimization of pectin grafted poly(N-isopropylacrylamide) hydrogels as vehicles for colon-targeted theophylline model drug release. The gels were prepared in the presence of N, N′–methylenebisacrylamide (MBAA) crosslinker and ceric ammonium nitrate (CAN) initiator under N₂ atmosphere. Optimum conditions, in terms of percent of grafting (%G), were determined as follows: pectin = 1.0 g, [NIPAAm] = 26.51 mM, [MBAA] = 0.65 mM, [CAN] = 0.073 mM, polymerization temperature = 30°C and time = 4.0 h. Hydrogels were characterized by FTIR, TGA, DSC, XRD and SEM. The formed hydrogel did not have a thermo-sensitivity behavior. The in vitro percent drug release was studied in terms of different percent of grafting and different polymerization temperatures under two pH values namely 5.5 and 7.4. Conclusively, the optimum colon-targeted vehicle properties that provide the least drug release at pH5.5 and the most drug release at pH7.4 were as follows: [NIPAAm] = 26.51 mM and [MBAA] = 0.56 mM, polymerization temperature = 30°C and %G = 55.5.     

Preparation and characteristics of multiple emulsions containing liquid crystals

In this paper, multiple emulsions containing liquid crystals were prepared successfully and the influence of formulation parameters on the formation mechanism was studied. Moreover, differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS) spectra analysis and stability analysis were used to characterise the property of them. The results showed that the chemical structure of water-in-oil (W/O) emulsifiers directly impacted on the formation of multiple structure, but the effect on the formation of liquid crystal structure was negligible. With the gap of the polarity between inner and outer liquid oils decreased, both multiple structure and liquid crystal structure were harder to form. The content of sodium chloride in internal aqueous phase, which should be neither too high nor too low, has great impact on the formulation of multiple structure. It was easier to form two structures simultaneously when the carbon chain length of fatty alcohols was closer to that of emulsifier C₂₂ alkyl polyglucoside (202). DSC elucidated the phase transitions of water in the liquid crystal layer and the W/O emulsions. SAXS indicated that the liquid crystal orientation was lamellar. The stability analysis showed that the presence of liquid crystal structure had a significant contribution to the stability of the multiple emulsions.     

Viscosity Variation During Evaporation of a Vegetable Oil Emulsion Stabilized by Tween 80R

The viscosity during evaporation was determined for emulsions in the system water, vegetable oil, a commercial surfactant, Tween 80^R, and the results related to the phases of the emulsion according to the phase diagram. The correlation between the viscosity and the fraction of liquid crystal in the emulsion was pronounced for the emulsions with the oil as the dispersed phase. For the emulsions with oil as the major phase, the effect was significantly less.     

Reconfigurable Photonic Capsules Containing Cholesteric Liquid Crystals with Planar Alignment

Cholesteric liquid crystals (CLCs) reflect selected wavelengths of light owing to their periodic helical structures. The encapsulation of CLCs leads to photonic devices that can be easily processed and might be used as stand‐alone microsensors. However, when CLCs are enclosed by polymeric membranes, they usually lose their planar alignment, leading to a deterioration of the optical performance. A microfluidics approach was employed to integrate an ultrathin alignment layer into microcapsules to separate the CLC core and the elastomeric solid membrane using triple‐emulsion drops as the templates. The thinness of the alignment layer provides high lubrication resistance, preserving the layer integrity during elastic deformation of the membrane. The CLCs in the microcapsules can thus maintain their planar alignment, rendering the shape and optical properties highly reconfigurable.