Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.     

微拟球藻脂质的亚临界提取工艺优化及其成分分析

采用亚临界丁烷提取微拟球藻脂质。在单因素试验的基础上采用正交试验对影响微拟球藻脂质提取率的因素进行优化,并测定了微拟球藻脂质的酸价、过氧化值、碘值、磷脂含量、脂肪组成以及脂肪酸组成。结果表明:亚临界丁烷提取微拟球藻脂质的最佳工艺条件为单次提取时间40 min、提取4次、提取温度45℃、料液比1∶8,在此条件下微拟球藻脂质提取率为41. 55%;提取的微拟球藻脂质呈深绿色油性糊状,其酸价(KOH) 20. 4 mg/g,过氧化值0. 001 g/100 g,碘值(I) 86. 0g/100 g,磷脂含量107. 28 mg/g;微拟球藻脂质中总脂肪含量为40. 22%,脂肪酸组成主要以不饱和脂肪酸为主,其中EPA含量为7. 21%。     

Surface energy and separation mechanics of droplet interface phospholipid bilayers

Droplet interface bilayers are a convenient model system to study the physio-chemical properties of phospholipid bilayers, the major component of the cell membrane. The mechanical response of these bilayers to various external mechanical stimuli is an active area of research because of its implications for cellular viability and the development of artificial cells. In this article, we characterize the separation mechanics of droplet interface bilayers under step strain using a combination of experiments and numerical modelling. Initially, we show that the bilayer surface energy can be obtained using principles of energy conservation. Subsequently, we subject the system to a step strain by separating the drops in a step-wise manner, and track the evolution of the bilayer contact angle and radius. The relaxation time of the bilayer contact angle and radius along with the decay magnitude of the bilayer radius were observed to increase with each separation step. By analysing the forces acting on the bilayer and the rate of separation, we show that the bilayer separates primarily through the peeling process with the dominant resistance to separation coming from viscous dissipation associated with corner flows. Finally, we explain the intrinsic features of the observed bilayer separation by means of a mathematical model comprising the Young–Laplace equation and an evolution equation. We believe that the reported experimental and numerical results extend the scientific understanding of lipid bilayer mechanics, and that the developed experimental and numerical tools offer a convenient platform to study the mechanics of other types of bilayers.     

绿原酸磷脂复合物固体分散体的体外溶出和药动学研究

为研究绿原酸磷脂复合物固体分散体(CA-PC-SD)的体外溶出以及体内药动学规律,采用HPLC法考察CA-PC-SD的体外溶出,大鼠灌胃后测定其血药浓度,并采用DAS 2.0软件分析计算药动学参数.结果显示:CA-PC-SD显著改善绿原酸磷脂复合物(CA-PC)的溶出效果,相较于原料药(CA)其相对生物利用度提高2.12倍.表明CA-PC-SD能显著改善CA-PC的体外溶出特性以及CA的口服生物利用率.     

High concentration of phosphorus is a distinctive feature of myelin. An X‐Ray elemental microanalysis study using freeze‐fracture scanning electron microscopy of rat sciatic nerve

We have used rat sciatic nerves submitted to freezing and freeze‐fracture to determine the elemental composition of small domains of the peripheral nerve studied at high resolution by scanning electron microscopy. We found that myelin of Schwann cells is unique in its high content in phosphorus (P) that was more than 10 times higher than P measured in any other cells. This high concentration in P makes myelin chemistry suitable of monitoring at the subcellular level using the herein described methodology. Microsc. Res. Tech. 78:537–539, 2015. © 2015 Wiley Periodicals, Inc.     

过氧化氢对大豆浓缩磷脂色泽的影响

大豆油加工过程中,向水化后的胶状物中加入过氧化氢,可以降低制备的大豆浓缩磷脂的色泽,但也会增加其过氧化值。研究发现,通过真空搅拌大豆浓缩磷脂,可以有效降低过氧化值,提升大豆浓缩磷脂的品质,提高附加值。     

Phospholipid complex as an approach for bioavailability enhancement of echinacoside

Context: Echinacoside (ECH) has been shown to possess a multitude of pharmacological activities, however, oral administered ECH failed to fulfill its therapeutic potential due to poor absorption and low bioavailability. Thus, there is a pressing need to develop a new oral dosage form to enhance its intestinal absorption and improve bioavailability.

Objective: The aim of this study was to formulate ECH into phospholipid complex (phytosome, PHY) to enhance intestinal absorption and oral bioavailability of ECH in vivo.

Methods: The PHY was prepared by a solvent evaporation method and was characterized by differential scanning calorimetry (DSC) and infrared spectroscopy (IR), and then the physicochemical properties, intestinal absorption and bioavailability of the PHY were investigated.

Results: Compared with the physical mixture (MIX) or ECH alone, the n-octanol/water partition coefficient (P) determination results showed that the lipophilicity of ECH was significantly enhanced by formation of PHY. Accordingly, the intestinal absorption rate (K_a) was improved to 2.82-fold and the effective permeability coefficient (P_eff) increased to 3.39-fold. The concentrations of ECH in rat plasma at different times after oral administration of PHY were determined by HPLC. Pharmacokinetic parameters of the PHY in rats were T_max?=?1.500?h, C_max?=?3.170?mg/mL, AUC_0–∞?=?9.375?mg/L?h and AUC_0–24?=?7.712?mg/L?h, respectively.

Conclusions: Compared with ECH alone or the MIX group, the relative bioavailability of ECH was increased significantly after formulation into PHY (p?相似文献   

A lyophilized etoposide submicron emulsion with a high drug loading for intravenous injection: preparation,evaluation, and pharmacokinetics in rats

Objective: To develop a submicron emulsion for etoposide with a high drug loading capacity using a drug–phospholipid complex combined with drug freeze-drying techniques. Methods: An etoposide–phospholipid complex (EPC) was prepared and its structure was confirmed by X-ray diffraction and differential scanning calorimetry analysis. A freeze-drying technique was used to produce lyophilized etoposide emulsions (LEPE), and LEPE was investigated with regard to their appearance, particle size, and zeta potential. The pharmacokinetic study in vivo was determined by the UPLC/MS/MS system. Results: It showed that EPC significantly improved the liposolubility of etoposide, indicating a high drug loading intravenous emulsion could be easily prepared by EPC. Moreover, the obtained loading of etoposide in the submicron emulsion was 3.0 mg/mL, which was three times higher than that of the previous liquid emulsions. The optimum cryoprotectant was trehalose (15%) in freeze-drying test. The median diameter, polydispersity index, and zeta potential of the optimum formulation of LEPE were 226.1 ± 5.1 nm, 0.107 ± 0.011, and ?36.20 ± 1.13 mV, respectively. In addition, these parameters had no significant change during 6 months storage at 4 ± 2°C. The main pharmacokinetic parameters exhibited no significant differences between LEPE and etoposide commercial solution except for area under the concentration–time curve and clearance. Conclusions: The stable etoposide emulsion with a high drug loading was successfully prepared, indicating the amount of excipients such as the oil phase and emulsifiers significantly decreased following administration of the same dose of drug, effectively reducing the metabolism by patients while increasing their compliance. Therefore, LEPE has a great potential for clinical applications.