在T型微通道内制备固体脂质纳米粒(SLN)的实验研究

研究了一种用T型微通道制备固体脂质纳米粒(solid lipid nanoparticles,SLN)的新方法.以softisan100(C_(10)～C_(18)的混合脂)丙酮溶液作为脂相,以Poloxamer 188水溶液为水相,用注射泵分别将脂相和水相注入T型通道的主道和支道内,两相在交叉口接触后形成明显的相界面,并继续沿主道向前流动.脂相中丙酮通过相界面迅速向水相扩散,随着流体的向前运动,脂相中脂的浓度不断增大至过饱和而形成固体脂质纳米粒(SLN).实验考察了两相流速和微通道尺寸对SLN粒径大小和粒径分布的影响.结果表明:在实验条件下,制得的SLN粒径在110～350 nm之间,多分散性指数小于0.24;T型通道交叉口的流场分布受两相相对流速的影响,并直接影响成粒规律,在不出现两相返混条件下,保持水相流速不变,SLN粒径随脂相流速增大而增大;保持脂相流速不变,粒径随水相流速的增大略有增大;通道尺寸越小所制得粒径也越小.     

微通道内载紫杉醇固体脂质纳米粒制备及工艺优化

目的:制备载紫杉醇固体脂质纳米粒。方法:微通道内采用溶剂扩散法制备脂质纳米粒,并通过正交优化制备工艺。结果:制备的纳米粒稳定性良好,平均粒径为(129.87±2.91)nm,包封率为(3.11±0.06)%,载药率为(43.67±0.24)%。结论:本研究制备的载药固体脂质纳米粒载药特性与重复性良好。     

Influence of Emulsifiers on the Formation and Crystallization of Solid Lipid Nanoparticles

The production of solid lipid nanoparticles by means of hot homogenization uses two different techniques: emulsification (liquid state) and crystallization (solid state). Both these processes depend on many parameters, such as composition, energy input, or geometry of the emulsification device. In former investigations known from the literature, the influence of the emulsifier concentration and the potential of controlling the polymorphic forms of the solidified particles were not investigated in detail. Here, these two factors were analyzed on the example of palm oil particles stabilized with emulsifiers suitable for foods. The influence of the emulsifier concentration on the resulting droplet and particle sizes is very high, up to a certain level. However, beside this influence, the polymorphic form of the solidified particles can be controlled by the right choice of emulsifier type and concentration.     

Preparation and Characterization of Catalase-Loaded Solid Lipid Nanoparticles Protecting Enzyme against Proteolysis

Catalase-loaded solid lipid nanoparticles (SLNs) were prepared by the double emulsion method (w/o/w) and solvent evaporation techniques, using acetone/methylene chloride (1:1) as an organic solvent, lecithin and triglyceride as oil phase and Poloxmer 188 as a surfactant. The optimized SLN was prepared by lecithin: triglyceride ratio (5%), 20-second + 30-second sonication, and 2% Poloxmer 188. The mean particle size of SLN was 296.0 ± 7.0 nm, polydispersity index range and zeta potential were 0.322-0.354 and -36.4 ± 0.6, respectively, and the encapsulation efficiency reached its maximum of 77.9 ± 1.56. Catalase distributed between the solid lipid and inner aqueous phase and gradually released from Poloxmer coated SLNs up to 20% within 20 h. Catalase-loaded SLN remained at 30% of H(2)O(2)-degrading activity after being incubated with Proteinase K for 24 h, while free catalase lost activity within 1 h.     

Stability of Solid Lipid Nanoparticles in the Presence of Liquid Oil Emulsions

The dissolution of solid lipid nanoparticles (d ~200 nm, SLN) by mass transfer of lipid molecules from liquid oil emulsion droplets (d ~200 nm) was investigated by differential scanning calorimetry (DSC) and nuclear magnetic resonance spectroscopy (NMR). The mass transfer of n-tetradecane to n-eicosane SLN resulted in the dissolution of the SLN over the course of several hours. The rate of dissolution increased with the tetradecane droplet to eicosane SLN ratio and was greater in the presence of a micelle forming surfactant (i.e., polyoxyethylene sorbitan monolaurate) compared to a protein (i.e., sodium caseinate). The rate of mass transfer was slower in a triacyglycerol system (i.e., liquid droplets of Miglyol and solid droplets of palm stearin, SLN) but could be accelerated by the presence of isopropanol (1.4%) in the aqueous phase. This work shows that even if SLN can be stabilized against aggregation, they may still dissolve due to diffusion of the lipids through the aqueous phase. Even a partial dissolution of SLN can dramatically change their functionality as delivery systems.     

正交试验法优化白花丹醌固体脂质纳米粒的制备工艺

目的:制备白花丹醌固体脂质纳米粒,并采用正交试验法优化其处方工艺.方法:采用乳化-超声分散法制备白花丹醌固体脂质纳米粒,以包封率为评价指标,通过单因素试验,考察了乳化温度、超声功率、大豆卵磷脂和泊洛沙姆188的用量比例等因素对白花丹醌包封率的影响,并以正交试验优选最佳处方工艺.结果:通过单因素与正交试验优选的最佳处方工艺为脂质用量80 mg、乳化剂用量150 mg(比例为1︰5)、乳化温度60℃、超声功率300 W.按照最佳处方工艺制备3批白花丹醌固体脂质纳米粒,平均粒径为168.93 nm,平均包封率为59.74％.结论:最佳处方工艺制备的白花丹醌固体脂质纳米粒具有较好的包封率,工艺稳定可行.     

固体线性酚醛树脂生产及其应用

介绍了固体线性酚醛树脂,包括:线性间甲酚甲醛树脂、线性间/对甲酚甲醛树脂,对于这两种线性酚醛树脂,根据用途不同而选择不同生产方法;同时介绍了固体线性酚醛树脂在某些领域里的新应用。     

Solid Lipid Nanoparticles: Effect of Carrier Oil and Emulsifier Type on Phase Behavior and Physical Stability

The impact of surfactant type and carrier oil type on the phase behavior and physical stability of emulsified tripalmitin was investigated. Solid lipid nanoparticles (SLNs) were prepared by homogenizing lipid and aqueous phases at a temperature (≈80 °C) above the melting point of tripalmitin, and then cooling the resulting oil-in-water emulsion to induce lipid droplet crystallization. When stored at 37 °C, tripalmitin particles had good long-term stability (d < 150 nm) when coated with Tween 20, but were prone to aggregation and gelation when coated with modified starch (MS). Conversely, when stored at ≤20 °C tripalmitin particles coated by MS were more stable to aggregation/gelation than those coated by Tween 20. Blending tripalmitin with low melting point lipids (either medium chain triglycerides or orange oil) prior to homogenization led to a considerable alteration in the SLN phase behavior and stability. DSC measurements indicated that the presence of the carrier oils reduced the crystallization temperature, melting temperature, and melting enthalpy of tripalmitin. In addition, the carrier oils improved the stability of SLNs to particle aggregation and gelation, although some particle coalescence still occurred. These results have important implications for formulating colloidal delivery systems for utilization within the food and other industries.     

Effect of Liquid Oil on the Distribution and Reactivity of a Hydrophobic Solute in Solid Lipid Nanoparticles

The performance of solid lipid nanoparticles is often modified by the addition of small amounts of liquid oil. The effects of added liquid lipid (tetradecane, C14) on the distribution and reactivity of the spin probe 4-phenyl-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl nitroxide (PTMIO) in solid lipid nanoparticles (eicosane, C20) were investigated as a function of storage time and temperature. Emulsions prepared with blends of C14:C20 (100 % C14, 90 % C20, 99 % C20, and 100 % C20) and stabilized by sodium caseinate (1 wt%) were stored at 21.5 °C or 5 °C for 5 or 24 h prior to EPR analyses. In the liquid C14 droplets the PTMIO partitioned between the droplet and aqueous phases (70 and 30 %, respectively) independent of storage conditions. However, the proportion of probe in droplets decreased with increasing crystalline C20 concentration. The fraction of PTMIO in droplets containing C20 decreased in the following sequence: 5 h at room temperature >24 h at room temperature >24 h at refrigerated temperature and was lower in droplets with a higher proportion of C20. The residual PTMIO in semicrystalline droplets has higher polarity and lower mobility than PTMIO in liquid oil droplets suggesting it is in a layer surrounding the crystalline lipid core, and partly immobilized by interaction with the surface layer. The model of PTMIO distribution was consistent with the kinetics of PTMIO reduction by aqueous ascorbate ions.     

In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin

The brain insulin metabolism alteration has been addressed as a pathophysiological factor underlying Alzheimer’s disease (AD). Insulin can be beneficial in AD, but its macro-polypeptide nature negatively influences the chances of reaching the brain. The intranasal (IN) administration of therapeutics in AD suggests improved brain-targeting. Solid lipid nanoparticles (SLNs) and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are promising carriers to deliver the IN-administered insulin to the brain due to the enhancement of the drug permeability, which can even be improved by chitosan-coating. In the present study, uncoated and chitosan-coated insulin-loaded SLNs and PLGA NPs were formulated and characterized. The obtained NPs showed desirable physicochemical properties supporting IN applicability. The in vitro investigations revealed increased mucoadhesion, nasal diffusion, and drug release rate of both insulin-loaded nanocarriers over native insulin with the superiority of chitosan-coated SLNs. Cell-line studies on human nasal epithelial and brain endothelial cells proved the safety IN applicability of nanoparticles. Insulin-loaded nanoparticles showed improved insulin permeability through the nasal mucosa, which was promoted by chitosan-coating. However, native insulin exceeded the blood-brain barrier (BBB) permeation compared with nanoparticulate formulations. Encapsulating insulin into chitosan-coated NPs can be beneficial for ensuring structural stability, enhancing nasal absorption, followed by sustained drug release.     

Evaluation of a Yarrowia lipolytica Strain Collection for Its Lipid and Carotenoid Production Capabilities

The oleaginous yeast Yarrowia lipolytica is capable of accumulating large amounts of fatty acids in the form of lipids which can serve as a platform polymer for a variety of applications. Additionally, through heterologous gene expression, Y. lipolytica is capable of producing carotenoids. Due to the observation that Y. lipolytica exhibits a high phenotypic inter‐strain variability, robotics and microwell scale cultivations are applied to examine 12 wild type strains of a Y. lipolytica collection. The strains are characterized with respect to their metabolic capabilities for fatty acid production as well as genetically manipulated to produce beta‐carotene. Furthermore, growth and production behavior of the strain collection at different temperatures as well as initial pH are assessed. A molecular discrimination between the strains is achieved by internal transcribed spacer (ITS)‐sequencing and polymerase chain reaction (PCR)‐based methods. The best performing strain with respect to lipid production produces ≈2% lipids per dry cell weight (DCW) and 8 mg g^?1 beta‐carotenoids in yeast nitrogen base (YNB) media. All strains show robust growth from 28 to 34 °C. Practical Applications: Unlocking nature's potential by screening natural isolates shows that even on inter‐strain level sufficient phenotypic diversity may arise. Automated growth‐based characterization of beta‐carotene‐producing strains in terms of media composition, effect of initial pH, and temperature tolerance shows that with modern cultivation techniques, rapid characterization of strain collections is feasible. Combining results of beta‐carotene and lipid formation could help to balance both pathways to improve the storage of hydrophobic compounds in the lipid droplets. The generalized findings could be further transferred to improve the production of any valuable compound, derived from the mevalonate pathway.     

A New Approach to the Dissolution Tests Management to Obtain Kinetic and Thermodynamic Data: Release of a Model Drug from Glyceryl Behenate Matrix Tablets

This study is focused on the use of glyceryl behenate as a lipophilic excipient of matrix tablets providing controlled drug release. The aim of this study is to evaluate activation energy (EA) and changes of the thermodynamic parameters (ΔH, ΔS, ΔG) of a dissolution process. These values, which have not yet been published, can lead to better understanding of a drug release mechanism and can extend the use options of glyceryl behenate in the pharmaceutical industry. Values of ΔH, ΔS, ΔG and E_A, providing an overall thermodynamic view on the studied matrix tablets, are evaluated based on the temperature-dependences of the release rate constant of a model drug (temperature range 25 - 45 °C). The studied lipophilic matrix tablets contain 10% to 50% of glyceryl behenate. Dissolution testing is carried out in an aqueous solution of HCl with addition of NaCl (pH1.2). Positive values of ΔH in the range of 3.83 to 56.13 kJ mol^-1 and positive values of ΔG indicate that the dissolution of the studied glyceryl behenate matrix tablets is an endothermic process which does not proceed spontaneously (in a temperature range of 25 - 45 °C). The negative slope of the linear curves of enthalpy-entropy compensation confirms the entropy-driven dissolution. Practical Applications : A better understanding of the dissolution process is an important aspect, e.g., in the field of drug formulation strategy. In this study, it is confirmed that the influence of temperature on the model drug release rate is negligible for tablets containing more than 40% of glyceryl behenate. It is an important result for drug design due to the reduction of risk of a possible dose dumping effect induced by temperature and the prevention of in vivo therapeutic failure.     

光敏热显成像材料中组分山嵛酸银与邻苯二甲酸的固相反应动力学

采用液相沉淀法合成了山嵛酸银与邻苯二甲酸的固相反应产物邻苯二甲酸二银,并通过元素分析、ICP-AES、FT-IR等方法对其进行了表征分析.在此基础上,采用X射线衍射K值分析法,在光敏热显成像材料热显影温度范围内(100～123 ℃),研究了山嵛酸银与邻苯二甲酸的固相反应过程.结果表明,山嵛酸银与邻苯二甲酸的固相反应为固态扩散控制过程.在一定的反应时间内,Jander方程能够较好地描述山嵛酸银与邻苯二甲酸的固相反应动力学,反应的表观活化能为84.5 kJ·mol-1,表观频率因子为7.06×107 min-1.在光敏热显成像材料热显影过程中,提高调色剂邻苯二甲酸在涂层中的扩散速度有利于提高其显影速率.     

In Vivo Evaluation of Praziquantel-Loaded Solid Lipid Nanoparticles against S. mansoni Infection in Preclinical Murine Models

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs’ suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in S. mansoni-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.     

Surfactant Effect on the Physicochemical Characteristics of Solid Lipid Nanoparticles Based on Pillar[5]arenes

Novel monosubstituted pillar[5]arenes containing both amide and carboxyl functional groups were synthesized. Solid lipid nanoparticles based on the synthesized macrocycles were obtained. Formation of spherical particles with an average hydrodynamic diameter of 250 nm was shown for pillar[5]arenes containing N-(amidoalkyl)amide fragments regardless of their concentration. It was established that pillar[5]arene containing N-alkylamide fragments can form spherical particles with two different sizes (88 and 223 nm) depending on its concentration. Mixed solid lipid nanoparticles based on monosubstituted pillar[5]arenes and surfactant (dodecyltrimethylammonium chloride) were obtained for the first time. The surfactant made it possible to level the effect of the macrocycle concentration. It was found that various types of aggregates are formed depending on the macrocycle/surfactant ratio. Changing the macrocycle/surfactant ratio allows to control the charge of the particles surface. This controlled property will lead to the creation of molecular-scale porous materials that selectively interact with various types of substrates, including biopolymers.     

地沟油制取生物柴油副产物甘油合成三醋酸甘油酯研究

三醋酸甘油酯作为甘油衍生物的一种,在化工、食品、医药行业应用广泛。文章以地沟油合成生物柴油副产物甘油为原料(精制后纯度为98.12%),酯化剂为冰醋酸,催化剂为磷钨酸,带水剂为甲苯。通过实验得到合成三醋酸甘油酯最优条件为:催化剂用量5.5%、带水剂0.54 m L/g、反应时间4 h、酸醇摩尔比为5,此条件下产率为97.24%。     

Storage Stability of Alpha-Lipoic Acid-loaded Lipid Nanoparticles

Alpha-lipoic acid-loaded lipid nanoparticles(ALA-LNs) were prepared by high pressure homogenization method.The influences of storage conditions such as time and temperature on the physical and chemical storage stability of ALA-LNs were studied in details.The stability was evaluated by particle size and polydispersity index,morphology of ALA-LNs,and capacity of ALA loading.The dilution and pH stability of ALA-LNs suspensions were also studied.After three months storage,the mean size of ALA-LNs at 4 and 40 ℃ was increased by 2.68% and 3.62% compared with the original size,respectively.ALA-LNs stored at 40 ℃ had ellipsoid shape and the mean size was about 152 nm(SD=23.6).The loading capacity of ALA at 40 ℃ was much higher than those stored at other two temperatures.The good dilution and pH stability were also demonstrated.The sample had good fluidity even at 4 ℃.     

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

Encapsulation of cargoes in nanocontainers is widely used in different fields to solve the problems of their solubility, homogeneity, stability, protection from unwanted chemical and biological destructive effects, and functional activity improvement. This approach is of special importance in biomedicine, since this makes it possible to reduce the limitations of drug delivery related to the toxicity and side effects of therapeutics, their low bioavailability and biocompatibility. This review highlights current progress in the use of lipid systems to deliver active substances to the human body. Various lipid compositions modified with amphiphilic open-chain and macrocyclic compounds, peptide molecules and alternative target ligands are discussed. Liposome modification also evolves by creating new hybrid structures consisting of organic and inorganic parts. Such nanohybrid platforms include cerasomes, which are considered as alternative nanocarriers allowing to reduce inherent limitations of lipid nanoparticles. Compositions based on mesoporous silica are beginning to acquire no less relevance due to their unique features, such as advanced porous properties, well-proven drug delivery efficiency and their versatility for creating highly efficient nanomaterials. The types of silica nanoparticles, their efficacy in biomedical applications and hybrid inorganic-polymer platforms are the subject of discussion in this review, with current challenges emphasized.     

高产油脂酵母的筛选及发酵条件的研究

采用苏丹黑染色法对6种酵母菌进行初筛及摇瓶发酵复筛,选出了油脂产量高的假丝酵母。并对假丝酵母摇瓶发酵条件进行优化,确定了最适培养条件为:初始pH值6.0,转速180 r.min-1,接种量10%,发酵周期4 d;最佳碳源为葡萄糖,最佳氮源为酵母膏。假丝酵母在优化条件下发酵后细胞量为16.4 g.L-1、油脂含量为12%、油脂产量为1.97 g.L-1,分别是优化前的142%、171%、245%。     

布洛芬固体脂质微颗粒的制备及其晶体构型研究

An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.