Osthole exhibits an antitumor effect in retinoblastoma through inhibiting the PI3K/AKT/mTOR pathway via regulating the hsa_circ_0007534/miR-214-3p axis

ContextOsthole shows antitumor effects in various tumours. Studies describing the effect of osthole on retinoblastoma (RB) are rare.ObjectiveThis study investigates the antitumor activity of osthole on RB.Materials and methodsRB cells were treated with different concentrations of osthole and then subjected to cell viability, colony formation, apoptosis, and western blot assays. The expression of hsa_circ_0007534 in RB tissues was determined by qRT-PCR. Hsa_circ_0007534 overexpression plasmid (oe-circ_0007534), miR-214-3p mimics and negative controls were transfected into RB cells to investigate cell viability. Athymic nude mice were injected with Y-79 cells to establish subcutaneous RB models. These mice were treated with osthole (0.5 mmol/kg) or corn oil for 36 days. Tumour tissues were collected for further analysis.ResultsOsthole inhibited cell viability of RB cells with an IC₅₀ of 200 μM for 24 h treatment and 120 μM for 48 h treatment, respectively. Hsa_circ_0007534 was increased significantly in RB tissues as compared to the matched nontumor tissues (p < 0.001). Oe-circ_0007534 counteracted the inhibitory effect of osthole on cell viability and colony numbers of Y-79 cells (p < 0.01). In vivo experiments indicated osthole significantly decreased the expression of hsa_circ_0007534 (p < 0.01) and increased the level of miR-214-3p in vivo. Furthermore, as compared to the control, osthole decreased the ratios of p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR (p < 0.01). However, hsa_circ_0007534 overexpression reversed the effect of osthole on the PI3K/AKT/mTOR pathway.Discussion and conclusionsOsthole exhibited an antitumour effect in RB, providing a scientific basis for further research and clinical applications of osthole in RB treatment.     

Effect of surface ligand density on cytotoxicity and pharmacokinetic profile of docetaxel loaded liposomes

Various biotin-modified liposomes incorporated with docetaxel (DTX) were prepared to study the effect of surface biotin density on the pharmacokinetic profile of the liposome. Four types of liposomes such as PEG modified liposome (PDL), 0.5% (mol) biotin modified liposome (0.5BDL), 1% (mol) biotin modified liposome (1BDL) and 2% (mol) biotin modified liposome (2BDL) were prepared using thin film dispersion method. The prepared liposomes were characterized by measuring encapsulation efficiency (EE), particle size, Zeta-potential, physical stability and drug release profiles in vitro. MTT assay was performed to elevate the cytotoxicity of liposomes on MCF-7 cells. In vivo evaluation was further performed to investigate the effect of biotin surface density on the pharmacokinetic profiles. All the prepared liposomes exhibited high encapsulation efficiency, small particle size, narrow particle distribution and sustained release profiles in vitro. In MTT assay, 0.5BDL showed largest tumor cell toxicity, compared with DTX solution. All liposomes containing DTX showed prolonged blood circulation in vivo, and 0.5BDL showed the longest circulation time among the biotin modified liposome. Surface modification of liposome had a negative impact on the circulation of liposomes in the blood, which needs to be considered when designing the ligand mediated targeting delivery systems. A proper amount of biotin liposome with 0.5% molar ratio is expected to produce the best anti-tumor effect.     

Chidamide stacked in magnetic polypyrrole nano-composites counter thermotolerance and metastasis for visualized cancer photothermal therapy

Photothermal therapy (PTT) has become one of the most promising therapies in cancer treatment as its noninvasiveness, high selectivity, and favorable compliance in clinic. However, tumor thermotolerance and distal metastasis reduce its efficacy, becoming the bottleneck of applying PTT in clinic. In this study, a chidamide-loaded magnetic polypyrrole nanocomposite (CMPP) has been fabricated as a visualized cancer photothermal agent (PTA) to counter tumor thermotolerance and metastasis. The efficacy of CMPP was characterized by in vitro and in vivo assays. As a result, this kind of magnetic polypyrrole nanocomposites were black spherical nanoparticles, possessing a favorable photothermal effect and the suitable particle size of 176.97 ± 1.45 nm with a chidamide loading rate of 12.92 ± 0.45%. Besides, comparing with PTT, CMPP exhibited significantly higher cytotoxicity and cellular apoptosis rate in two tumor cell lines (B16-F10 and HepG2). In vivo study, the mice showed obvious near-infrared (NIR) and magnetic resonance imaging (MRI) dual-modal imaging at tumor sites and sentinel lymph nodes (SLNs); on the other hand, magnetic targeting guided CMPP achieved a cure level on melanoma-bearing mice through preventing metastasis and thermotolerance. Overall, with high loading efficiency of chidamide and strong magnetic targeting to tumor sites and SLNs, CMPP could significantly raise efficiency of PTT by targeting tumor thermotolerance and metastasis, and this strategy may be exploited therapeutically to upgrade PTT with MPP as one of appropriate carriers for histone deacetylase inhibitors (HDACis).     

阳离子脂质材料和聚乙二醇对脂质体细胞转染率及膜流动性的影响阳离子脂质材料和聚乙二醇对脂质体细胞转染率及膜流动性的影响

目的制备包封荧光素钠（FS）的脂质体，考察阳离子脂质材料（DC-chol）和聚乙二醇（PEG）对脂质体包封率、细胞转染率及膜流动性的影响。方法以FS作为模型物质，制备并分离脂质体，测定脂质体包封率；通过观察荧光光谱的变化考察FS与脂质体膜之间的相互作用；以HepG₂ 2.2.15为细胞模型观察脂质体对FS细胞转染率的影响；通过荧光偏振技术考察阳离子脂质材料和PEG对脂质体膜流动性的影响。结果阳离子脂质材料和PEG能提高脂质体包封率（0.64％～86.57％）、细胞转染率（2.18％～48.46％）及脂质体膜流动性，PEG分子质量的增大有利于包封率、转染率的提高，并增加脂质体膜的流动性。结论在脂质体处方中加入阳离子脂质材料和高分子量的PEG有利于提高包封率、细胞转染率及增加脂质体膜的流动性。     

黄芩苷脂质体的制备及在小鼠体内的分布

目的制备黄芩苷脂质体并考察其在小鼠体内的分布 ,为黄芩苷脂质体治疗乙型肝炎提供依据。方法用逆相蒸发法制备黄芩苷脂质体 ,测定其粒径及包封率 ,观察静脉注射黄芩苷脂质体及黄芩苷水溶液后 ,不同时间在小鼠体内的分布。结果 5批黄芩苷脂质体平均粒径为 (36 0± 4 2 )nm ,平均包封率为 (5 6 .0± 5 .3) %。黄芩苷脂质体主要分布于肝、脾 ,以肝脏中分布最多 ,而在血中清除加快。结论逆相蒸发法制备黄芩苷脂质体条件易控制 ,重复性好 ,可获得较高包封率和符合肝靶向要求的脂质体 ;黄芩苷脂质体具有一定的肝靶向性 ,可延缓黄芩苷在体内的代谢为乙肝治疗提供新途径。     

Targeted delivery of quercetin by biotinylated mixed micelles for non-small cell lung cancer treatment

Lung cancer is the leading cause of cancer death world-wide and its treatment remains a challenge in clinic, especially for non-small cell lung cancer (NSCLC). Thus, more effective therapeutic strategies are required for NSCLC treatment. Quercetin (Que) as a natural flavonoid compound has gained increasing interests due to its anticancer activity. However, poor water solubility, low bioavailability, short half-life, and weak tumor accumulation hinder in vivo applications and antitumor effects of Que. In this study, we developed Que-loaded mixed micelles (Que-MMICs) assembled from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine–poly(ethylene glycol)–biotin (DSPE–PEG–biotin) and poly(ethylene glycol) methyl ether methacrylate–poly[2-(dimethylamino) ethyl acrylate]–polycaprolactone (PEGMA–PDMAEA–PCL) for NSCLC treatment. The results showed that Que was efficiently encapsulated into the mixed micelles and the encapsulation efficiency (EE) was up to 85.7%. Cellular uptake results showed that biotin conjugation significantly improved 1.2-fold internalization of the carrier compared to that of non-targeted mixed micelles. In vitro results demonstrated that Que-MMICs could improve cytotoxicity (IC₅₀ = 7.83 μg/mL) than Que-MICs (16.15 μg/mL) and free Que (44.22 μg/mL) to A549 cells, which efficiently induced apoptosis and arrested cell cycle. Furthermore, Que-MMICs showed satisfactory tumor targeting capability and antitumor efficacy possibly due to the combination of enhanced permeability and retention (EPR) and active targeting effect. Collectively, Que-MMICs demonstrated high accumulation at tumor site and exhibited superior anticancer activity in NSCLC bearing mice model.     

脂质体包裹的反义寡核苷酸逆转耐甲氧西林金黄色葡萄球菌耐药性的研究

目的：用人工合成磷脂二棕榈酰磷脂酰胆碱（dipalmitoyl phosphatidylcholine，DPPC），二肉豆蔻酰磷脂酰甘油（dimyristoyl phosphatidylglycerol，DMPG）制备反义寡核苷酸阴离子脂质体并研究脂质体包裹的抑制耐甲氧西林金黄色葡萄球菌（methicillin resistant staphylococcus aureus，MRSA）耐药基因表达信号传导通路中BlaRlmRNA表达的反义寡核苷酸（antisense phosphothioate oligodeoxynucleotides，AS-ODNs）对MRSA耐药性的影响。方法：设计合成AS-ODNs；薄膜分散冻干法制备其脂质体；透射电镜观察脂质体的形态；离心纯化脂质体并用紫外分光光度计测定包封率、渗漏率；振荡法检测体外释放度；平板克隆形成实验计数菌落数CFU；微量法测定细菌生长曲线。结果：反义寡核苷酸阴离子脂质体大小均匀，为圆球体，包封率为77．38％，冷冻条件下保存1月后渗漏率为0．18％，体外释放度实验表明24h后约60％的药物从脂质体中释放，反义寡核苷酸脂质体可显著抑制MRSA生长，脂质体包裹的不同剂量的AS-ODNs中MRSA的菌落形成单位（CFU）与空白对照组比较明显减少，具有剂量依赖性，且效果明显优于未被脂质体包裹的AS-ODNs。结论：采用薄膜分散冻干法制备反义寡核苷酸阴离子脂质体，包封率较高，质量稳定，反义寡核苷酸脂质体能逆转MRSA的耐药性，效果明显优于单用AS-ODNs，可作为反义寡核苷酸进入细菌的载体。     

Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease

The blood–brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer’s disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptor-related protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110 nm, and a round morphology. Cell uptake observations, BBB models in vitro, and imaging analysis in vivo showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis in vivo demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD.     

Optimization,and in vitro and in vivo evaluation of etomidate intravenous lipid emulsion

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, −36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.     

去氢骆驼蓬碱脂质体制备工艺优化及抗肝癌活性

目的 制备去氢骆驼蓬碱脂质体并对其制备工艺进行优化，评价脂质体的相关表征及对肝癌细胞的毒性。方法 用薄膜水化法制备去氢骆驼蓬碱脂质体。以包封率作为评价指标，以大豆卵磷脂和药物的质量比、大豆卵磷脂与胆固醇的质量比和超声时间作为评价因素对脂质体包封率的影响。并对脂质体的粒径、Zeta电位、外观和稳定性进行评价。CCK-8法对比去氢骆驼蓬碱和去氢骆驼蓬碱脂质体的抗肝癌细胞增殖活性。结果 最优制备工艺：大豆卵磷脂和药物的质量比为11.4：1，大豆卵磷脂与胆固醇的质量比为4.4：1，超声时间为33 min。在此条件下制备的脂质体的包封率为81.88%，粒径为143.65 nm，Zeta电位为-12.68 mV，低温环境稳定性良好，具有缓释效应。去氢骆驼蓬碱脂质体的抗肝癌细胞增殖活性大于裸药。结论 所制得的去氢骆驼蓬碱脂质体包封率和稳定性均符合标准。将去氢骆驼蓬碱制备成为脂质体能提高其抗肝癌细胞增殖活性。     

Controllable release of pirfenidone by polyvinyl alcohol film embedded soft contact lenses in vitro and in vivo

To increase the amount of pirfenidone (PFD) loaded in polyvinyl alcohol (PVA) film embedded soft contact lens (SCL), and evaluate its function of sustaining delivery of drug in vitro and in vivo. Drug loading efficiency within PVA film and SCLs, drug release from SCLs in vitro, and the effects of parameters of SCLs and external environment on drug release in vitro were evaluated by ultraviolet–visible spectrophotometer at 312 nm. Safety of SCLs was evaluated in vitro by transformed human corneal epithelial cell. Safety in vivo was determined by optical coherence tomography and histology of anterior segment of rabbits. Drug release study in tear fluid and aqueous humor were measured by ultra-performance liquid chromatography. SCLs had smooth surface and were fit for experimental rabbits. Amount of PFD in PVA film and SCLs were 153.515 μg ± 12.508 and 127.438 μg ± 19.674, respectively, PFD in PVA film was significantly higher than SCLs (p=.006) and closed to 150 μg (targeting amount of PFD to be loaded). Thickness of SCLs, molecular weight of PVA, and amount of PVA used in SCLs affected drug release in vitro significantly. Thickness of PVA film and amount of drug in SCLs had no effect on drug release rate in vitro. SCLs were safe in vitro and in vivo, PFD released from SCLs could be detected around 12 hours in tears and aqueous humor, and the concentration of drug was higher than eye drop at all detected time points while amount of PFD in SCLs was lower than eye drop. Drug loaded PVA film embedded SCLs may be a promising ocular drug delivery system.     

支链淀粉修饰双嘧达莫脂质体的制备及其在小鼠体内的组织分布

目的研究支链淀粉修饰双嘧达莫(DIP)脂质体的制备方法并考察其在小鼠体内的组织分布。方法 采用薄膜-分散法制备普通DIP脂质体；合成两亲性的棕榈酰化支链淀粉并用其修饰DIP脂质体；比较修饰前后包封率、zeta电位、平均粒径和径距的变化；采用反相高效液相法测定小鼠组织中的DIP浓度。结果修饰后DIP脂质体的包封率降低，zeta电位增加，平均粒径和径距无明显变化；普通脂质体可以增强DIP在肺部、肝脏和脾脏的分布，而较之普通脂质体，支链淀粉修饰的脂质体可以进一步增加肺部DIP水平，同时减少DIP在肝脏和脾脏的分布，并延长在肺部的滞留时间。结论与普通脂质体和注射液比较，支链淀粉修饰的脂质体可以改变DIP在小鼠体内的组织分布，具有显著的肺靶向性。     

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn²⁺ nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both in vitro and in vivo. Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The in vitro relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH = 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated in vitro using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the r₁ relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM⁻¹·s⁻¹. Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, p=.041). The in vivo analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice (p < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.     

Construction,characterization, and bioavailability evaluation of honokiol-loaded porous starch by melting method without any solvent

In the present study, the porous starch (PS) was used as an efficient carrier of honokiol (HK), and the HK-loaded PS (HPS) delivery system was prepared by melting method without using organic solvents. Its physical-chemical properties, solubility and oral bioavailability were also investigated. The obtained results proved that the HK in the HPS was mostly amorphous when it was loaded into the PSs with 87.54 ± 1.52% of encapsulation efficiency (EE) and 12.51 ± 0.22% of drug loading (DL) capacity. The water-solubility of the HPS was increased to 115.27 ± 2.92 μg/mL (pH = 1.2, artificial gastric juice (AGJ)), 161.58 ± 3.42 (pH = 6.8, artificial intestinal juice (AIJ)) and 148.5 ± 1.89 μg/mL (pH = 5.5, simulated tumor microenvironment), being 6.07, 4.38 and 4.87-folds higher than free HK. In vitro dissolution tests showed the HK was significantly higher from HPS than from free HK. Furthermore, compared with free HK, the release rate and the bioavailability was also substantially improved for HK from the HPS. Meanwhile, the HPS generated a higher inhibition to HepG2 cells than free HK.     

Construction of pH-sensitive targeted micelle system co-delivery with curcumin and dasatinib and evaluation of anti-liver cancer

Nanomedicine delivery systems can achieve precise drug delivery and reduce toxic side effects compared with traditional drug delivery methods, but further development is still needed to eliminate obstacles such as multiple drug co-delivery, uncontrolled drug-release, and drug-resistance. Herein, we designed a dual drug-loaded nanosystem (THCD-NPs) that selectively transports and targets tumor cells for the treatment of liver cancer. In this drug delivery system, hyaluronic acid (HA)-conjugated curcumin (Cur) and d-α-tocopherol acid polyethylene glycolsuccinate (TPGS) were used as selective drug-carrying vehicles to deliver dasatinib (DAS) to cancer cells for combined administration. The mean size of the nanoparticles was approximately 66.14 ± 4.02 nm with good in vitro stability. The nanoparticles were pH sensitive and could accelerate drug release at low pH conditions. In vitro experiments showed that THCD-NPs were significantly cytotoxic to HepG2 cells and could be effectively taken up by these cells. Detailed investigations also demonstrated its pro-apoptotic activity. In vivo NIR fluorescence imaging showed that the nanoparticles could accumulate efficiently at the tumor site. Meanwhile, in vivo experiments showed that THCD-NPs significantly inhibited tumor growth and reduced the toxic side effects of free drugs in a mouse solid tumor model. In short, the nanoparticles we prepared provide a new idea for the treatment of liver cancer.     

以叶酸受体为靶向的阳离子脂质体的制备与性质考察

为了研制一种能通过叶酸受体途径靶向肿瘤细胞的叶酸受体靶向脂质体，将叶酸(folate，folic acid，F)、 聚乙二醇二胺(polyoxyethylene-bis-amine，NH₂-PEG-NH₂)、 琥珀酸酐(succinic anhydride，SUC)和二硬脂酰磷脂酰乙醇胺(distearoylphosphatidylethanolamine，DSPE)按序共价连接， 并使用薄层色谱和飞行时间质谱确证合成产物为叶酸-聚乙二醇-二硬脂酰磷脂酰乙醇胺(folate-polyethyleneglycol-distearoylphosphatidylethanolamine，F-PEG-DSPE)。膜材选用二棕榈酰磷脂酰胆碱(dipalmitoylphosphatidylcholine，DPPC)， 3β-［N-(N′,N′-二甲基胺乙基)胺基甲酰基］胆固醇(3β-［N(N′,N′-dimethylaminoethane) carbamoyl］ cholesterol，DC-Chol)和F-PEG-DSPE，以10∶10∶0.75(摩尔比)的配比，以荧光素标记的阴离子葡聚糖(dextran fluorescein anionic，DFA)为模型，用薄膜分散法制备含DFA的叶酸受体靶向脂质体，其包封率较高(>55%)、稳定性好，平均粒径为144 nm，体外释放慢。MTT法考察其对细胞的毒性结果表明该阳离子脂质体具有一定的细胞毒性，在低浓度时(0.012 5～0.1 μmol·L^{-1)脂质体的细胞毒性与DC-chol浓度成正比。流式细胞技术检测KB细胞和HepG2细胞对DFA脂质体的摄取，结果表明叶酸受体靶向的长循环阳离子脂质体能提高细胞对脂质体的摄取。该研究为进一步研究叶酸受体靶向阳离子脂质体在肿瘤基因治疗中的应用提供了理论基础。}     

Green synthesis of gold nanoparticles from Dendrobium officinale and its anticancer effect on liver cancer

A novel gold nanoparticle (Do-AuNP) was successfully synthesized from water extracts of traditional Chinese medicine Dendrobium officinale (DO) without using any extra chemicals regents. The physicochemical properties of Do-AuNPs were analyzed by transmission electron microscopy, dynamic light scattering, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The amount of DO extract on the AuNPs was about 13%. In order to evaluate the anti-tumor efficiency and biosafety, the inhibitory rate of HepG2 cells and survival rate of L02 cells were performed in vitro, and the immunohistochemical analysis of H&E, Ki-67, and TUNEL staining were conducted in vivo. Our results demonstrated that Do-AuNP had better anti-tumor efficiency compared with DO extraction alone without increasing toxicity in vivo and in vitro. The present study provides useful information for Do-AuNP as a new nanomedicine for liver cancer.     

Characterization and in-vivo ocular absorption of liposome-encapsulated acyclovir.

The potential of liposomes as an in-vivo ophthalmic drug delivery system for acyclovir was investigated. The drug-membrane interaction was evaluated by means of differential scanning calorimetry analysis. These experiments showed that acyclovir is able to interact with both positively and negatively charged membranes via electrostatic or hydrogen bonds. No interaction was observed with neutral membranes made up of dipalmitoylphosphatidylcholine. Different liposome preparation procedures were carried out to encapsulate acyclovir. The drug encapsulation mainly depends on the amount of water which the liposome system is able to entrap. In the case of multilamellar vesicles, charged systems showed the highest encapsulation efficiency. No particular difference in the encapsulation efficiency was observed for oligolamellar vesicles prepared with the reverse-phase evaporation technique. Oligolamellar liposomes showed the highest acyclovir encapsulation parameters and had release profiles similar to those of multilamellar liposomes. In-vivo experiments using male New Zealand albino rabbits were carried out to evaluate the aqueous humour concentration of acyclovir bioavailability. The most suitable ophthalmic drug delivery system was oligolamellar systems made up of dipalmitoylphosphatidylcholine-cholesterol-dimethyldioctadecyl glycerole bromide (7:4:1 molar ratio), which presented the highest encapsulation capacity and were able to deliver greater amounts of the drug into the aqueous humour than a saline acyclovir solution or a physical liposome/drug blend.     

Development and Characterization of a Liposome Preparation by a pH-Gradient Method

Abstract— A pH gradient across liposome bilayers was established in order to load a model drug (orciprenaline sulphate) into liposome vesicles. This method of liposome loading resulted in yields as high as 80–85% encapsulation. An eight-step process was designed to scale-up the process and was evaluated. In this process a diafiltration technique was successfully used to remove the excess orciprenaline sulphate present in the external medium. Finally, drug-loaded liposomes were lyophilized using lactose as an internal and external liposomal cryoprotectant. Five-month stability data for the liposomes is reported. An HPLC technique was used to determine the drug concentration and a laser light-scattering technique was employed to determine the liposome vesicle size and polydispersity factor. Liposomes prepared by the pH-gradient method showed high encapsulation efficiency. Upon storage at 2–8°C the vesicle size increased and encapsulation efficiency decreased with time. These phenomena are attributed to gradual fusion of liposomes and loss of drug to the extra-liposomal media.     

白细胞介素2脂质体的制备及其抗肿瘤作用的研究

采用逆相蒸发法制备稳定的白细胞介素2（IL－2）大单层脂质体，对其包封率、稳定性及活性进行了测定。建立C57BL／6小鼠荷瘤动物模型，通过给荷瘤小鼠腹腔注射空白脂质体、单纯IL-2及IL-2脂质体来比较其在肿瘤生长中的抑制作用，结果3组抑癌率分别为4．26％、34．04％和54.60％。空白脂质体组与单纯对照组相比尤显著性差异（P＞0．05），脂质体-IL-2组与单纯IL-2组之间存在显著性差异（P＜0．05），抑瘤率提高了20.6％。