固体脂质纳米粒的制备和研究进展

固体脂质纳米粒是近年来发展起来的一类新型载体给药系统，由于其长效、无毒、良好靶向性等优点，拥有广阔的发展前景。本文参考了国内外诸多有代表性的论文，就这类载体的制备、常用检测分析方法、剂型应用及其发展趋势等方面加以阐述。     

Preparation and Pharmacokinetic Evaluation of Tashinone IIA Solid Lipid Nanoparticles

Tashinone IIA loaded solid lipid nanoparticles (TA-SLN) coated with poloxamer 188 was prepared by emulsification/evaporation. The TA-SLN was characterized by transmission electron microscope and dynamic light scattering (DLS). The results showed that the TA-SLN had an average diameter of 98.7 nm with a zeta potential of ? 31.6 mv and the drug loading of 4.6% and entrapment efficiency of 87.7%. In vitro release experiment showed that the release of Tashinone IIA from TA-SLN was in accordance with the Weibull equation. The best model fitting experimental data was a two-compartment open model with first-order. The area under curve of plasma concentration–time (AUC) and mean residence time (MRT) of TA-SLN were much higher than those of Tashinone IIA control solution (TA-SOL). The results of pharmacokinetic studies in rabbits indicated that the formulation of TA-SLN was successful in providing a delivery of slow release of Tashinone IIA.     

脂质纳米粒在抗衰老中的应用

文章综述了脂质纳米粒在抗衰老中的应用,简要介绍了衰老的原因以及目前主要抗衰老物质和手段,阐述了脂质纳米粒的优点及其在抗衰老应用中的优势,并列举了部分抗衰老脂质纳米粒产品的应用情况。     

Evaluation of Solid Dispersions of Clofazimine

ABSTRACT

Clofazimine (CLF) was formulated with polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) as a solid solid dispersion (SSD) to increase the aqueous solubility and dissolution rate of the drug. Different molecular weights of PEG (1500, 4000, 6000, and 9000 Da) and PVP (14,000 and 44,000 Da) were used in different drug:carrier weight ratios (1:1, 1:5, and 1:9) and their effect on the dissolution performance of the drug was evaluated in USP Type 2 apparatus using 0.1 N HCl medium. The dissolution rate was compared with corresponding physical mixtures, a currently marketed soft gelatin capsule product, and free CLF. The effect of different methods of preparation (solvent/melt) on the dissolution rate of CLF was evaluated for PEG solid dispersions. Saturation solubility and phase solubility studies were carried out to indicate drug:carrier interactions in liquid state. Infrared (IR) spectroscopy and X-ray diffraction (XRD) were used to indicate drug:carrier interactions in solid state. Improvement in the drug dissolution rate was observed in solid dispersion formulations as compared to the physical mixtures. The dissolution rate improved with the decreasing weight fraction of the drug in the formulation. Polyvinyl pyrrolidone solid dispersion systems gave a better drug release profile as compared to the corresponding PEG solid dispersions. The effect of molecular weight of the PEG polymers did not follow a definite trend, while PVP 14,000 gave a better dissolution profile as compared to PVP 44,000. Improvement in saturation solubility of the drug in the solid dispersion systems was noted in all cases. Further, IR spectroscopy indicated drug:carrier interactions in solid state in one case and XRD indicated reduction in the crystallinity of CLF in another. It was concluded that solid-dispersion formulations of Clofazimine can be used to design a solid dosage form of the drug, which would have significant advantages over the currently marketed soft gelatin capsule dosage form.     

Preparation and Optimization of Dry PLGA Nanoparticles by Spray Drying Technique

The aim of this article was to evaluate the potential of poly lactide-coglycolide (PLGA) nanoparticles (NPs) as carriers for controlling release of doxorubicin (DOX) via a spray drying technique. The challenge was to entrap a hydrophilic molecule into a lipophilic core molecule of PLGA. To achieve this objective, we modified conventional approach of drug loading to spray drying technique. The eight formulations of nanoparticles were prepared by modified double emulsion and solvent evaporation technique followed by spray drying using 2³ factorial designs. PLGA (A) and PVA (B) and stirring speed (C) were used as independent variables where particle size (Y₁), entrapment efficiency (Y₂) and percentage of drug release at the 32 hour (Y₃) were taken as dependant variables. The results showed that the method is easy and efficient for the entrapment of the drug as well as the formation of spherical nanoparticles. This modification improved DOX entrapment efficiency relative to controls real loadings up to 40%. The in vitro release studies indicated the DOX loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of DOX-PLGA nanoparticles.     

Aerosol Spray Drying Guided Synthesis of Ultrasmall Alloyed Bimetallic Nanoparticles Supported on Silica for Catalytic Semihydrogenation

Supported bimetallic nanoparticles (NPs) with ultrasmall sizes and homogeneous alloying are attractive for catalysis. However, facile synthesis of this type of material remains very challenging. Here, the aerosol drying impregnation method for rapid, scalable, and general synthesis of silica-supported bimetallic NPs is proposed. The method relies on aerosol spray drying to promote the mixing and dispersing of binary metal precursors on SiO₂. It is capable of controlling the composition and size of bimetallic NPs and avoids the use of expensive metal complex salts and complicated experiment procedures. Twelve permutations combining a noble metal (Pd, Ru, and Pt) and a base one (Fe, Co, Ni, and Cu) with ultrasmall sizes (1.4–2.2 nm in average size), uniform dispersion, and good alloying are synthesized. Interesting activity and selectivity trends in catalytic semihydrogenation of phenylacetylene over the supported Pd-based NPs can be observed. The silica-supported PdNi NPs deliver both high activity and styrene selectivity. Spectroscopic and density functional theory calculation results reveal the improved chemoselectivity originated from the suitably down-shifted d-band center of the PdNi NPs inducing an increased energy barrier for overhydrogenation and a weakened styrene adsorption.     

The Role of Temperature and Lipid Charge on Intake/Uptake of Cationic Gold Nanoparticles into Lipid Bilayers

Understanding the molecular mechanisms governing nanoparticle–membrane interactions is of prime importance for drug delivery and biomedical applications. Neutron reflectometry (NR) experiments are combined with atomistic and coarse‐grained molecular dynamics (MD) simulations to study the interaction between cationic gold nanoparticles (AuNPs) and model lipid membranes composed of a mixture of zwitterionic di‐stearoyl‐phosphatidylcholine (DSPC) and anionic di‐stearoyl‐phosphatidylglycerol (DSPG). MD simulations show that the interaction between AuNPs and a pure DSPC lipid bilayer is modulated by a free energy barrier. This can be overcome by increasing temperature, which promotes an irreversible AuNP incorporation into the lipid bilayer. NR experiments confirm the encapsulation of the AuNPs within the lipid bilayer at temperatures around 55 °C. In contrast, the AuNP adsorption is weak and impaired by heating for a DSPC–DSPG (3:1) lipid bilayer. These results demonstrate that both the lipid charge and the temperature play pivotal roles in AuNP–membrane interactions. Furthermore, NR experiments indicate that the (negative) DSPG lipids are associated with lipid extraction upon AuNP adsorption, which is confirmed by coarse‐grained MD simulations as a lipid‐crawling effect driving further AuNP aggregation. Overall, the obtained detailed molecular view of the interaction mechanisms sheds light on AuNP incorporation and membrane destabilization.     

A Combinatorial Library of Lipid Nanoparticles for RNA Delivery to Leukocytes

Lipid nanoparticles (LNPs) are the most advanced nonviral platforms for small interfering RNA (siRNA) delivery that are clinically approved. These LNPs, based on ionizable lipids, are found in the liver and are now gaining much attention in the field of RNA therapeutics. The previous generation of ionizable lipids varies in linker moieties, which greatly influences in vivo gene silencing efficiency. Here novel ionizable amino lipids based on the linker moieties such as hydrazine, hydroxylamine, and ethanolamine are designed and synthesized. These lipids are formulated into LNPs and screened for their efficiency to deliver siRNAs into leukocytes, which are among the hardest to transfect cell types. Two potent lipids based on their in vitro gene silencing efficiencies are also identified. These lipids are further evaluated for their biodistribution profile, efficient gene silencing, liver toxicity, and potential immune activation in mice. A robust gene silencing is also found in primary lymphocytes when one of these lipids is formulated into LNPs with a pan leukocyte selective targeting agent (β₇ integrin). Taken together, these lipids have the potential to open new avenues in delivering RNAs into leukocytes.     

Characteristics of Bicalutamide Solid Dispersions and Improvement of the Dissolution

ABSTRACT

The purpose of our study was to formulate and evaluate bicalutamide (BL) solid dispersions (SD). The physicochemical properties were evaluated by differential scanning calorimetry (DSC), Fourier-Transform infrared (FT-IR) spectroscopy, Powder X-ray diffractometry (PXRD), dissolution studies, and stability studies. The dissolution studies demonstrated that the dissolution of BL from BL-SD increased with an increase in carrier content (PVP K30). X-ray assays and DSC results both confirmed the amorphous state of BL in BL-SD. Stability studies conducted after 6 months showed that BL exhibited excellent stability in the solid dispersion of PVP K30 (1:5).     

A Facile Method to Coat Nanoparticles with Lipid Bilayer Membrane: Hybrid Silica Nanoparticles Disguised as Biomembrane Vesicles by Particle Penetration of Concentrated Lipid Layers

Natural membrane vesicles, including extracellular vesicles and enveloped viruses, participate in various events in vivo. To study and manipulate these events, biomembrane-coated nanoparticles inspired by natural membrane vesicles are developed. Herein, an efficient method is presented to prepare organic–inorganic hybrid materials in high yields that can accommodate various lipid compositions and particle sizes. To demonstrate this method, silica nanoparticles are passed through concentrated lipid layers prepared using density gradient centrifugation, followed by purification, to obtain lipid membrane-coated nanoparticles. Various lipids, including neutral, anionic, and cationic lipids, are used to prepare concentrated lipid layers. Single-particle analysis by imaging flow cytometry determines that silica nanoparticles are uniformly coated with a single lipid bilayer. Moreover, cellular uptake of silica nanoparticles is enhanced when covered with a lipid membrane containing cationic lipids. Finally, cell-free protein expression is applied to embed a membrane protein, namely the Spike protein of severe acute respiratory syndrome coronavirus 2, into the coating of the nanoparticles, with the correct orientation. Therefore, this method can be used to develop organic–inorganic hybrid nanomaterials with an inorganic core and a virus-like coating, serving as carriers for targeted delivery of cargos such as proteins, DNA, and drugs.     

Dissolution, Solubility, XRD, and DSC Studies on Flurbiprofen-Nicotinamide Solid Dispersions

Flurbiprofen-nicotinamide solid dispersions were prepared by the fusion method. The solid dispersions were evaluated for dissolution rate. The drug-carrier interaction in the liquid and solid states were studied by using phase solubility analysis, phase diagram, X-ray diffraction (XRD), and differential scanning calorimentry (DSC). Solid dispersions gave fast and rapid dissolution of flurbiprofen compared with the pure drug and the physical mixture. Phase diagram and DSC indicated that flurbiprofen and nicotinamide form a eutectic mixture. The aqueous solubility of flurbiprofen was enhanced in the presence of nicotinamide.     

Dissolution,Solubility, XRD,and DSC Studies on Flurbiprofen-Nicotinamide Solid Dispersions

Flurbiprofen-nicotinamide solid dispersions were prepared by the fusion method. The solid dispersions were evaluated for dissolution rate. The drug-carrier interaction in the liquid and solid states were studied by using phase solubility analysis, phase diagram, X-ray diffraction (XRD), and differential scanning calorimentry (DSC). Solid dispersions gave fast and rapid dissolution of flurbiprofen compared with the pure drug and the physical mixture. Phase diagram and DSC indicated that flurbiprofen and nicotinamide form a eutectic mixture. The aqueous solubility of flurbiprofen was enhanced in the presence of nicotinamide.     

堇青石水基流延坯片的干燥动力学研究

以纳米堇青石粉体为原料,聚丙烯酸钠为分散剂,聚乙烯醇为粘结剂,聚乙二醇为增塑剂,通过水基流延成型制备了堇青石陶瓷基片。研究了流延坯片的干燥工艺及干燥动力学。结果表明,堇青石水基流延坯片干燥过程分为恒速干燥和降速干燥两个阶段。在恒速干燥阶段,坯片表面水分的蒸发占主导地位。随着干燥过程的进行,水分在坯片内部的扩散传输开始占据主导。在降速干燥阶段,由于坯片内高分子三维网状结构的束缚作用和高分子链上羟基(-OH)的亲和作用,干燥速率减慢。干燥温度过高会破坏坯片内部三维结构,导致坯片表面疏松。干燥温度为25℃时,得到的堇青石生坯表面光滑,柔韧性好,致密度高。     

PVP在水相金纳米粒子表面吸附过程的研究

运用紫外可见吸收光谱,在水相金溶胶体系中研究了聚乙烯吡咯烷酮(PVP)在金纳米粒子表面的吸附.实验结果表明:PVP吸附在金纳米粒子的表面,使金纳米粒子的特征吸收峰的峰位红移15nm左右且强度下降.根据金溶胶中PVP加入量和特征吸收峰的变化,提出了PVP对溶胶中金纳米粒子的表面包裹经过的过程.     

Solubility of Solid Dispersions of Pizotifen Malate and Povidone

We analyzed the physicochemical characteristics of solid dispersions of pizotifen malate and povidone (Kollidon 12) at different proportions; we used X-ray diffraction, infrared spectrometry, and differential scanning calorimetry (DSC) and tested the solubility of the solid dispersions in equilibrium. The results were compared with findings for physical mixtures with the same proportions. A solid dispersion with a drug proportion of 16%–17% formed a eutectic mixture. Solubility of pizotifen malate increased with the proportion of drug in the solid dispersion up to a drug:polymer ratio of 40:60. The hydrotropic effect of the polymer also favored solubility: In physical mixtures, this effect was greatest at a drug:polymer ratio of 10:90; solubility at this proportion was equal to that of the solid dispersion at the same proportion.     

Spray Drying of Aqueous Solutions of Inorganic and Organic Materials

Since the characteristics of the solution and the hot drying air have major influence on the physical, structural, and granulometric properties of the powders obtained by spray drying, it is very important to properly select the process conditions which will result with the formation of a powder of desired properties. For that reason, the influence of process conditions on the properties of the powders produced by spray drying has been investigated on a laboratory scale. The aqueous solutions of two organic (glycine and pentaerythritol) and three inorganic (sodium chloride, potassium chloride and potassium sulfate) materials have been chosen. During very fast spray drying it is impossible to distinguish individual steps of simultaneous processes (crystallization and drying). Knowledge of solubility data and crystallization kinetics of selected materials may help to explain what happens during spray drying.

The experiments have been performed at different drying air temperature, flow rate of the solution and of the spraying air. The obtained powders are mostly crystalline and agglomerated. Investigated process conditions influence the polymorphic composition of glycine obtained by spray drying. In order to have real information about the granulometric composition of powders it is necessary to perform microscopic analysis of the obtained crystals.     

固体绝缘材料真空干燥的瞬态湿分迁移

固体绝缘材料是电气行业的主要原材料，真空处理工艺是改善其性能的关键技术之一。本文分析了真空干燥过程中湿分的非稳态迁移机理，为民工产品的真空处理工艺提供了理论依据。     

蒸发冷却空调术语标准化的必要性及意义的探讨

介绍了蒸发冷却空调标准及术语的制定背景,分析了蒸发冷却空调术语存在的主要问题,并指出了蒸发冷却空调术语标准化的意义。