Development of Phosphatidylethanolamine Liposomes That Efficiently Retain Encapsulated Vinorelbine Bitartrate

A hydrophilic and temperature-induced degradation drug, vinorelbine bitartrate (VB)-loaded phosphatidylethanolamin sterically stabilized liposomes (PSLs) were prepared by the thin film hydration method. Liposomes were made of phosphatidylethanolamine: cholesteryl: oleic acid (PE: CHOL: OA, 6:4:3 mass/mass). The mean particle size of the PSLs ranged from 600 to 650 nm. The transmission electron microscope (TEM) images displayed that the shape of the PSLs was multilamellar vesicles with smooth surface. The highest entrapment efficiency (EE) and drug loading capacity (DL) could reach up to 81.2 and 16.6%, respectively. The studies of drug release showed that the drug release could last for much more than 48 hours. The PSLs was evaluated by comparing the rate of release of encapsulated VB in different phosphate buffer solution (PBS).     

LC Tissue Distribution Study of Paeonol in Rats after Oral Administration

Paeonol, an important constituent of the traditional Chinese medicine Cortex Moutan, has a variety of bioactivity. A simple and sensitive HPLC?CUV method has been developed for analysis of paeonol in different rat tissue (heart, liver, spleen, lung, kidney, and brain). Bio-samples were prepared by simple protein precipitation, and separation of paeonol was achieved on a C₁₈ column with methanol?C2% glacial acetic acid solution 70:30 (v/v) as mobile phase at a flow rate of 1.0 mL min^?1. UV detection was at 274 nm and the column temperature was 30 °C. Linearity was good between 0.025 and 5.0 ??g mL^?1 (r ² ?? 0.9990) for tissue samples. Inter-day and intra-day accuracy (as relative error, RE) and precision (as relative standard deviation, RSD) were <5.94 and 6.05%, respectively. The limit of detection was 0.025 ??g mL^?1 and extraction recovery for all samples was ??85.86%. The method was successfully applied to a tissue-distribution study after oral administration of 40 mg kg^?1 paeonol to healthy Sprague?CDawley rats. The study showed that paeonol was quickly distributed and eliminated after oral administration; liver and kidney were the major distribution tissues of paeonol in rats, and paeonol quickly passed through the blood?Cbrain barrier. It was also found there was no long-term accumulation of paeonol in rat tissues.     

Quantitative Determination of Adrenaline Hydrochloride Injection and Noradrenaline Bitartrate Injection by a New HPLC Method via Substitute for Reference Substance

An HPLC method for quantitative determination of adrenaline hydrochloride injection and noradrenaline bitartrate injection was established and validated with a substitute for the reference substance.Phenylephrine hydrochloride was selected as the substitute for the reference substance of adrenaline and noradrenaline bitartrate.The correction factor of phenylephrine hydrochloride with respect to the reference substance of adrenaline and noradrenaline bitartrate was determined under defined conditions.Adrenal...     

Pharmacokinetics and Tissue Distribution of DVDMS-2 in Tumor-bearing Mice

DVDMS-2 is a novel candidate for photodynamic therapy of tumors. The purpose of the present study was to assess the distribution and elimination of DVDMS-2 in mice bearing hepatoma 22 tumors. DVDMS-2 (1, 2 and 4 mg kg⁻¹) was injected intravenously into the mice, extracted from biological tissues and quantified using a fluorescence assay. The data obtained were processed with WinNonlin pharmacokinetic software. The fluorescence assay established for DVDMS-2 quantification was a rapid, reproducible, sensitive and specific method with good linearity. The pharmacokinetics of DVDMS-2 in tumor-bearing mice conformed to a two-compartment model. DVDMS-2 accumulated in tumor tissue to a greater extent than adjacent tissues (skin, muscle) and sustained a relatively high-level concentration 12 to 24 h following administration, which may be the optimal treatment time point. In conclusion, DVDMS-2 selectively accumulated in tumor tissue and was eliminated at a rapid rate in tumor-bearing mice, suggesting that DVDMS-2 may have few side effects, including skin phototoxicity. The present study established the pharmacokinetic characteristics of DVDMS-2, which may be beneficial in future clinical study.     

Pharmacokinetics and Tissue Distribution Study of Tryptanthrin in Rats by RP-HPLC with DAD Detector

A simple RP-LC-UV method was established for the determination of tryptanthrin in plasma and different tissues of rats. The separation was achieved by HPLC on a C₁₈ column with a mobile phases composed of acetonitrile–water (47:53, v/v), UV detection was used at 251 nm. Good linearity was found between 0.0183–1.1712 μg mL⁻¹ (r ² = 0.999) for plasma and 0.0937–1.7568 μg mL⁻¹ for the tissue samples, respectively (r ² ≥ 0.9932). The intra- and inter-day precisions expressed as the relative standard deviation for the method were 0.92–6.01 and 1.06–9.11 %, respectively. The relative recoveries of tryptanthrin ranged from 95.26 to 97.89 % for plasma and 82.55 to 114.99 % for tissue homogenates (except heart). The developed method was successfully applied to the pharmacokinetics and tissue distribution research after orally administration of a 56-mg kg⁻¹ dose of tryptanthrin to healthy SD rats. The main pharmacokinetics distribution results showed that liver, lung, small intestine, and large intestine were the major distribution tissues of tryptanthrin in rats, and that tryptanthrin had difficulty in crossing the blood–brain barrier.

     

Pharmacokinetics and Tissue Distribution Study of Tryptanthrin in Rats by RP-HPLC with DAD Detector

A simple RP-LC-UV method was established for the determination of tryptanthrin in plasma and different tissues of rats. The separation was achieved by HPLC on a C₁₈ column with a mobile phases composed of acetonitrile?Cwater (47:53, v/v), UV detection was used at 251?nm. Good linearity was found between 0.0183?C1.1712???g?mL^?1 (r ²?=?0.999) for plasma and 0.0937?C1.7568???g?mL^?1 for the tissue samples, respectively (r ²????0.9932). The intra- and inter-day precisions expressed as the relative standard deviation for the method were 0.92?C6.01 and 1.06?C9.11?%, respectively. The relative recoveries of tryptanthrin ranged from 95.26 to 97.89?% for plasma and 82.55 to 114.99?% for tissue homogenates (except heart). The developed method was successfully applied to the pharmacokinetics and tissue distribution research after orally administration of a 56-mg?kg^?1 dose of tryptanthrin to healthy SD rats. The main pharmacokinetics distribution results showed that liver, lung, small intestine, and large intestine were the major distribution tissues of tryptanthrin in rats, and that tryptanthrin had difficulty in crossing the blood?Cbrain barrier.     

Preclinical Pharmacokinetics and Bioavailability of Oxypeucedanin in Rats after Single Intravenous and Oral Administration

Oxypeucedanin, a furanocoumarin extracted from many traditional Chinese herbal medicines, has a variety of pharmacological effects. However, the independent pharmacokinetic characteristics and bioavailability of this compound remains elusive. In this study, a rapid, sensitive, and selective method using ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS) was developed for evaluating the intravenous and oral pharmacokinetics of oxypeucedanin. After intravenous administration of oxypeucedanin (2.5, 5, and 10 mg/kg), and intragastric administration of oxypeucedanin (20 mg/kg), blood samples were collected periodically from the tail vein. The plasma concentration-time curves were plotted, and the pharmacokinetic parameters were calculated using a non-compartmental model analysis. After intravenous administration of oxypeucedanin (single dosing at 2.5, 5, and 10 mg/kg) to rats, the pharmacokinetics fit the linear kinetics characteristics, which showed that some parameters including average elimination half-life (T_1/2Z of 0.61~0.66 h), mean residence time (MRT of 0.62~0.80 h), apparent volume of distribution (V_Z of 4.98~7.50 L/kg), and systemic clearance (CL_Z of 5.64~8.55 L/kg/h) are dose-independent and the area under concentration-time curve (AUC) increased in a dose-proportional manner. Single oral administration of oxypeucedanin (20 mg/kg) showed poor and slow absorption with the mean time to reach the peak concentration (T_max) of 3.38 h, MRT of 5.86 h, T_1/2Z of 2.94 h, and a mean absolute bioavailability of 10.26% in rats. These results provide critical information for a better understanding of the pharmacological effect of oxypeucedanin, which will facilitate its research and development.     

Pharmacokinetics,Prostate Distribution and Metabolic Characteristics of Four Representative Flavones after Oral Administration of the Aerial Part of Glycyrrhiza uralensis in Rats

(1) Background: The aerial part of G. uralensis had pharmacological effects against chronic non-bacterial prostatitis (CNP), and flavonoids are the main efficacy components. The purpose of this study was to obtain the pharmacokinetics, prostate distribution and metabolic characteristics of some flavonoids in rats. (2) Methods: The prototype flavones and the metabolites of four representative flavonoids, namely puerarin, luteolin, kaempferol and pinocembrin in plasma, prostate, urine and feces of rats were analyzed by UPLC-Q-Exactive Orbitrap-MS. In addition, the pharmacokinetic parameters in plasma and distribution of prostate of four components were analyzed by HPLC-MS/MS. (3) Results: In total, 22, 17, 22 and 11 prototype flavones were detected in the prostate, plasma, urine and feces, respectively. The metabolites of puerarin in the prostate are hydrolysis and glucose-conjugated products, the metabolites of kaempferol and luteolin in the prostate are methylation and glucuronidation, and the metabolites of pinocembrin in the prostate are naringenin, oxidation, sulfation, methylation and glucuronidation products. The t_1/2 of puerarin, luteolin, kaempferol and pinocembrin was 6.43 ± 0.20, 31.08 ± 1.17, 18.98 ± 1.46 and 13.18 ± 0.72 h, respectively. The concentrations of the four flavonoids in prostate were ranked as kaempferol > pinocembrin > luteolin > puerarin. (4) Conclusions: Methylation and glucuronidation metabolites were the main metabolites detected in the prostate. A sensitive and validated HPLC–MS/MS method for simultaneous determination of puerarin, luteolin, kaempferol and pinocembrin in rat plasma and prostate was described, and it was successfully applied to the pharmacokinetic and prostate distribution studies.     

Design and Synthesis of Lipidic Organoalkoxysilanes for the Self‐Assembly of Liposomal Nanohybrid Cerasomes with Controlled Drug Release Properties

This paper reports the facile design and synthesis of a series of lipidic organoalkoxysilanes with different numbers of triethoxysilane headgroups and hydrophobic alkyl chains linked by glycerol and pentaerythritol for the construction of cerasomes with regulated surface siloxane density and controlled release behavior. It was found that the number of triethoxysilane headgroups affected the properties of the cerasomes for encapsulation efficiency, drug loading capacity, and release behavior. For both water‐soluble doxorubicin (DOX) and water‐insoluble paclitaxel (PTX), the release rate from the cerasomes decreased as the number of triethoxysilane headgroups increased. The slower release rate from the cerasomes was attributed to the higher density of the siloxane network on the surface of the cerasomes, which blocks the drug release channels. In contrast to the release results with DOX, the introduction of one more hydrophobic alkyl chain into the cerasome‐forming lipid resulted in a slower release rate of PTX from the cerasomes due to the formation of a more compact cerasome bilayer. An MTT viability assay showed that all of these drug‐loaded cerasomes inhibited proliferation of the HepG2 cancer cell line. The fine tuning of the chemical structure of the cerasome‐forming lipids would foster a new strategy to precisely regulate the release rate of drugs from cerasomes.     

Brain Concentration of Ginsenosides and Pharmacokinetics after Oral Administration of Mountain‐cultivated Ginseng

Mountain‐cultivated ginseng (MCG ) can be considered a mimic of wild ginseng, whose seeds are sowed artificially, cultivated in the natural environment, and returned to the wild state before being used clinically. Cultivated ginseng (CG ) and MCG are mainly used as the commercial material for clinical applications. However, MCG is much more expensive but effective than CG . The aim of this study is to explore the differences in the pharmacokinetics and brain concentration of Rg1, Re, Rb1, and Rd after oral administration of MCG , CG, and pure ginsenosides. An ultra‐performance liquid chromatography‐tandem mass spectrometry method was developed and validated to determine the concentration of the four ginsenosides in rat plasma and brain tissue. Compared with the pure group, the area under the curve (AUC) of all the four ginsenosides for CG and MCG increased. The mean brain concentrations of the four ginsenosides were found to be 10‐ to 15‐fold lower than the corresponding contents in the plasma, and the poor permeability of ginsenosides into blood–brain barrier was indicated by the low concentrations of the four ginsenosides.     

Amplification of the Cotton Effect of a Single Chromophore through Liposomal Ordering—Stereochemical Assignment of Plakinic Acids I and J

A dramatic effect is observed when acyclic N‐(2‐naphthamides) of medium‐chain 1‐amino‐2‐methylalkanes are partially ordered with the help of liposomes: the Cotton effect arising from π–π* transitions of the terminal naphthamide chromophor is enormously enhanced. This effect was exploited to assign the configuration of new polyketide peroxides such as 1 from the sponge Plakortis halichondroides.

     

刺五加叶黄酮脂质体和滴丸的药动学差异比较

采用液质联用(LC-MS/MS)方法,分析刺五加叶黄酮脂质体、刺五加叶滴丸和刺五加叶黄酮提取物经大鼠灌胃给药后其主要成分金丝桃苷的药代动力学和生物利用度,考察刺五加叶黄酮的适宜剂型。用PKsolver软件进行药代动力学数据处理,大鼠灌胃刺五加叶黄酮提取物、刺五加叶滴丸和刺五加叶黄酮脂质体后测得金丝桃苷的最大血药浓度(C_(max))分别为(210.24±10.3)、(254.12±9.2)、(349.34±12.5)μg/L;0~t时间内药时曲线面积(AUC_(0-t))分别为(30.7±2.7)、(35.01±1.98)、(45.2±2.8)μg/(m L·min);平均驻留时间(MRT)分别为(334.42±75.36)、(394.56±90.26)和(640.35±84.26)min。结果表明,刺五加叶黄酮脂质体血药达峰浓度增加,清除速率降低,药时曲线下面积加大,生物利用度显著提高,脂质体有望成为刺五加叶黄酮的适宜剂型。     

Liposomal Bilayer as a Carrier of Rosa canina L. Seed Oil: Physicochemical Characterization,Stability, and Biological Potential

Rosa canina L. seeds are rich in bioactive components that can add value to the various formulations. The focus of the study was the development of liposomes for R. canina oil to protect its sensitive compounds and prolong their shelf-life. Oil-loaded liposomes were characterized via the determination of the particle size, polydispersity index (PDI), zeta potential, conductivity, mobility, density, surface tension, viscosity, and stability. Raman and FT-IR spectroscopy were employed to investigate the chemical composition of the non-treated and UV-treated samples, and the presence of different interactions. Antioxidant and antimicrobial activities were examined as well. The liposome size was 970.4 ± 37.4 nm, the PDI 0.438 ± 0.038, the zeta potential −32.9 ± 0.8 mV, the conductivity 0.068 ± 0.002 mS/cm, the mobility −2.58 ± 0.06 µmcm/Vs, the density 0.974 ± 0.004 g/cm³, the surface tension 17.2 ± 1.4 mN/m, and the viscosity 13.5 ± 0.2 mPa•s. The Raman and FT-IR spectra showed the presence of lipids, fatty acids, polyphenols, and carotenoids. It was approved that the oil compounds were distributed inside the phospholipid bilayer and were combined with the membrane interface of the bilayer. The UV irradiation did not cause any chemical changes. However, neither the pure oil nor the oil-loaded liposomes showed any antimicrobial potential, while the antioxidant capacity of the oil-loaded liposomes was significantly low. The sizes of the liposomes did not change significantly during 60 days of storage. Due to the proven stability of the oil-loaded liposomes, as well as the liposome’s ability to protect the sensitive oil compounds, their potential application in the pharmaceutical and cosmetic formulations could be investigated with a focus on the skin regeneration effects.     

Stealth Liposomes (PEGylated) Containing an Anticancer Drug Camptothecin: In Vitro Characterization and In Vivo Pharmacokinetic and Tissue Distribution Study

Numerous attempts to overcome the poor water solubility of cam ptothecin (CPT) by various nano drug delivery systems are described in various sources in the literature. However, the results of these approaches may be hampered by the incomplete separation of free CPT from the formulations, and this issue has not been investigated in detail. This study aimed to promote the solubility and continuous delivery of CPT by developing long-lasting liposomes using various weights (M.W. 2000 and 5000 Daltons) of the hydrophilic polymer polyethylene glycol (PEG). Conventional and PEGylated liposomes containing CPT were formulated via the lipid film hydration method (solvent evaporation) using a rotary flash evaporator after optimising various formulation parameters. The following physicochemical characteristics were investigated: surface morphology, particle size, encapsulation efficiency, in vitro release, and formulation stability. Different molecular weights of PEG were used to improve the encapsulation efficiency and particle size. The stealth liposomes prepared with PEG₅₀₀₀ were discrete in shape and with a higher encapsulation efficiency (83 ± 0.4%) and a prolonged rate of drug release (32.2% in 9 h) compared with conventional liposomes (64.8 ± 0.8% and 52.4%, respectively) and stealth liposomes containing PEG₂₀₀₀ (79.00 ± 0.4% and 45.3%, respectively). Furthermore, the stealth liposomes prepared with PEG₅₀₀₀ were highly stable at refrigeration temperature. Significant changes were observed using various pharmacokinetic parameters (mean residence time (MRT), half-life, elimination rate, volume of distribution, clearance, and area under the curve) of stealth liposomes containing PEG₂₀₀₀ and PEG₅₀₀₀ compared with conventional liposomes. The stealth liposomes prepared with PEG₅₀₀₀ showed promising results with a slow rate of release over a long period compared with conventional liposomes and liposomes prepared with PEG₂₀₀₀, with altered tissue distribution and pharmacokinetic parameters.     

三氧化二砷磁性纳米粒的表征及其在小鼠组织中的药代动力学

通过溶剂转移法制备了三氧化二砷铁氧体磁性纳米粒(As₂O₃-MNPs). 利用扫描电镜/能谱分析、红外光谱(IR)和差示扫描量热法(DSC)等技术对其进行了表征. 选择正常小鼠肝脏作为靶区, 在外加磁场的诱导下, 考察As₂O₃-MNPs在小鼠体内的组织药代动力学特征, 以此反映该磁性纳米粒的磁靶向性效果. 红外光谱分析结果显示, As₂O₃-MNPs中存在磁性材料MgFe₂O₄; DSC分析表明, 制备磁性纳米粒所用材料As₂O₃、乳酸羟基乙酸共聚物(PLGA)和铁氧体之间没有明显的相互作用, 可用于磁性纳米粒的制备; 能谱分析结果显示As₂O₃和磁性材料MgFe₂O₄ 不是吸附于纳米粒的表面, 而是包裹于其中; 磁场组小鼠肝脏组织中药物浓度-时间曲线下面积(AUC_0-∞)、达峰浓度(c_max)和消除半衰期(t_1/2)均明显大于非磁场组(P<0.05), 说明As₂O₃-MNPs在正常小鼠体内有良好的磁靶向性分布. 所制备的三氧化二砷磁性纳米粒稳定性好, 靶向性强, 在肿瘤治疗方面具有良好的应用前景.     

Pharmacokinetics of 10‐hydroxycamptothecin–tetrandrine liposome complexes in rat by a simple and sensitive ultra‐high performance liquid chromatography with tandem mass spectrometry

10‐Hydroxycamptothecin is a drug to cure various cancers. However, the 10‐hydroxycamptothecin cannot be widely applied in clinics due to fast elimination and resistance of various cancers to the drug. Nevertheless, co‐treatment with tetrandine is known to reverse the resistance of multi‐drug resistant cancers, and may present an effective strategy to improve the efficacy of 10‐hydroxycamptothecin. In order to improve the bioavailability and prolong the treatment time of the 10‐hydroxycamptothecin in vivo, we prepared 10‐hydroxycamptothecin‐tetrandrine liposome complexes with 10‐hydroxycamptothecin as the basic anticancer drug, tetrandrine and liposomes as carriers. In this article, an ultra‐high performance liquid chromatography tandem mass spectrometry method for the analysis of 10‐hydroxycamptothecin and tetrandrine in plasma has been developed, validated, and utilized to compare the pharmacokinetics of both drugs in the original dosage form and administered as liposome complexes. According to the pharmacokinetic parameters of mean residence time, half‐life period and clearance rate, the 10‐hydroxycamptothecin‐tetrandrine liposome complexes prolongs the retention and circulation time of 10‐hydroxycamptothecin in vivo, achieving a good sustained release effect. To the best of our current knowledge, the pharmacokinetic properties of 10‐hydroxycamptothecin‐tetrandrine liposome complexes in rats have not been reported yet. Our study can provide a helpful reference for further related study.