Vincristine-doxorubicin co-loaded artificial low-density lipoproteins towards solid tumours.

To construct an artificial low-density lipoprotein (aLDL) that highly mimics low-density lipoprotein (LDL) in vivo, and deliver vincristine (VCR) - doxorubicin (DOX) simultaneously, the 100 nm and 35 nm DOX-VCR-aLDLs (DV-aLDLs) were constructed, then the physicochemical characteristics were evaluated. Through in vitro inverse gravity diffusion experiment, the tumour cake and sphere model experiment, draw a conclusion that the diffusion of 35 nm DV-aLDLs was stronger than 100 nm DV-aLDLs, and the tumour retention of 35 nm DV-aLDLs was better than the DV-solution. In addition, the three-dimension (3D) in vivo distribution imaging of aLDLs was performed on HepG-2 tumour-bearing nude mice, followed by the biodistribution and therapeutic efficacy on these xenograft models.

A novel preparative method for nanoparticle albumin-bound paclitaxel with high drug loading and its evaluation both in vitro and in vivo.

We developed a novel preparative method for nanoparticle albumin-bound (nab) paclitaxel with high drug loading, which was based on improved paclitaxel solubility in polyethylene glycol (PEG) and self-assembly of paclitaxel in PEG with albumin powders into nanoparticles. That is, paclitaxel and PEG were firstly dissolved in ethanol, which was subsequently evaporated under vacuum. The obtained liquid was then mixed with human serum albumin powders.

Development and Evaluation of Ropivacaine Loaded Poly(Lactic-Co-Glycolic Acid) Microspheres with Low Burst Release.

Background: The local anesthetic drugs, especially ropivacaine, were considered favorable analgesia for postoperative management because of their effective local pain relief and low adverse effects. However, the short half-life and the resulting in bolus doses lead to the indistinctive improvement of these drugs in postoperative pain relief. Therefore, the ropivacaine microspheres with sustained release and low initial burst release were anticipated.

Establishment and evaluation of a Beagle model of grade III pancreatic trauma.

Pancreatic trauma (PT) is a severe abdominal injury that is often combined with multiple organ injury. It is a severe disease that is difficult to diagnose and has a high mortality rate, particularly for grade III PT. The pathogenesis, disease progress and complications have not been fully investigated due to the lack of a reliable animal model.

In vitro toxicity assessment of nanocrystals in tissue-type cells and macrophage cells.

Nanocrystals (NCs), a type of innovative material particle, are a potential drug delivery platform that aims to improve the bioavailability of hydrophobic drugs. However, due to the lack of consideration of their toxicity, existing studies have not investigated whether the nanoscale properties of NCs, such as particle sizes, may lead to NC-induced toxicity. Because of the disparity between the rapid development of NCs and the lack of studies regarding NC toxicity, the present study investigated possible NC toxicity and clarified the relationship between particle sizes and NC toxicity.

Vincristine liposomes with smaller particle size have stronger diffusion ability in tumor and improve tumor accumulation of vincristine significantly.

The passive targeting is the premise of active targeting that could make nanocarrier detained in tumor tissue. The particle size is the most important factor that influences the diffusion and distribution of nanoparticle both and . In order to investigate the relationship between particle size and diffusion ability, two kinds of liposome loaded with Vincristine (VCR-Lip) were prepared.

Simultaneous determination of metolazone and valsartan in plasma by on-line SPE coupled with liquid chromatography/tandem mass spectrometry.

Combination of metolazone (0.5 mg) and valsartan (80 mg) has been verified as a promising therapy treatment for hypertension. In order to facilitate to pharmacokinetic research, it needs a method for the simultaneously determination of metolazone and valsartan in biological samples.

Dual Tumor-Targeting Nanocarrier System for siRNA Delivery Based on pRNA and Modified Chitosan.

Highly specific and efficient delivery of siRNA is still unsatisfactory. Herein, a dual tumor-targeting siRNA delivery system combining pRNA dimers with chitosan nanoparticles (CNPPs) was designed to improve the specificity and efficiency of siRNA delivery. In this dual delivery system, folate-conjugated and PEGylated chitosan nanoparticles encapsulating pRNA dimers were used as the first class of delivery system and would selectively deliver intact pRNA dimers near or into target cells.

Apoferritin Nanocage for Brain Targeted Doxorubicin Delivery.

An ideal brain-targeted nanocarrier must be sufficiently potent to penetrate the blood-brain barrier (BBB) and sufficiently competent to target the cells of interest with adequate optimized physiochemical features and biocompatibility. However, it is an enormous challenge to the researchers to organize the above-mentioned properties into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials.

Simultaneous Determination of Felodipine and Metoprolol in Beagle Dog Plasma by Online SPE-LC-MS/MS and Its Application in a Pharmacokinetic Study.

In order to overcome deficiencies for simultaneously determining felodipine (FDP) and metoprolol (MPL) with low recovery and low sensitivity, a new online SPE coupled with the liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method for the simultaneous quantitative determination of FDP and MPL in beagle dog plasma was established. The SPE extraction of FDP and MPL was performed on a Retain PEP Javelin column (10 × 2.1 mm, 5 μm), while the chromatographic separation was achieved on a ZORBAX SB-C18 (50 × 2.

Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma.

Therapeutic outcome for the treatment of glioma was often limited due to drug resistance and low permeability of drug across the multiple physiological barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier (BTB). In order to overcome these hurdles, we designed T7 and A7R dual peptides-modified liposomes (abbreviated as T7/A7R-LS) to efficiently co-delivery doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma.

An Accelerated Release Method of Risperidone Loaded PLGA Microspheres with Good IVIVC.

Background: A long release period lasting several days or several weeks is always needed and thereby it is tedious and time consuming to screen formulations of such microspheres with so long release period and evaluate their release profiles in vitro with conventional long-term or "real-time" release method. So, an accelerated release testing of such system is necessary for formulation design as well as quality control purpose. The purpose of this study is to obtain an accelerated release method of risperidone loaded poly(lactic-co-glycolic acid) (PLGA) microspheres with good in vitro/in vivo correlation (IVIVC).

Chiral analysis of ammuxetine enantiomers in dog plasma using online SPE/liquid chromatography with tandem mass spectrometric detection after precolumn chiral derivatization.

Ammuxetine (AMT), a novel chiral antidepressant candidate compound, exhibits better antidepression effects than duloxetine in different animal models. In this article, a chiral derivatization method, combined with online solid phase extraction (online SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), was developed for the chiral separation of AMT enantiomers after administration of racemic AMT to dogs. The derivatization reaction employed 2,3,4,6-tetra-O-acetyl-b-glucopyr-anosyl isothiocyanate (GITC) as a precolumn chiral derivatization reagent.

Development and Evaluation of High Bioavailable Sustained-Release Nimodipine Tablets Prepared with Monolithic Osmotic Pump Technology.

Background: Frequent administration caused by short half-life and low bioavailability due to poor solubility and low dissolution rate limit the further application of poorly water-soluble nimodipine, although several new indications have been developed. To overcome these shortcomings, sophisticated technologies had to be used since the dose of nimodipine was not too low and the addition of solubilizers could not resolve the problem of poor release.

Objective: The purpose of this study was to obtain sustained and complete release of nimodipine with a simple and easily industrialized technology.

A photo-responsive peptide- and asparagine-glycine-arginine (NGR) peptide-mediated liposomal delivery system.

The conjugation of tunable peptides or materials with nanocarriers represents a promising approach for drug delivery to tumor cells. In this study, we report the development of a novel liposomal carrier system that exploits the cell surface binding synergism between photo-sensitive peptides (PSPs) and targeting ligands. The positive charges of the lysine residues on the cell-penetrating peptides (CPPs) were temporarily caged by the photolabile-protective groups (PG), thereby forming a PSP.

The development and evaluation of a subcutaneous infusion delivery system based on osmotic pump control and gas drive.

A novel, self-administration drug delivery system for subcutaneous infusion was developed and evaluated. The device includes two main components: an osmotic tablet controlled gas actuator and a syringe catheter system. The sodium carbonate in the osmotic pump tablet will release into the surround citric acid solution and produce CO gas, which will drive the drug solution into subcutaneous tissue.

Protection Provided by a Gabexate Mesylate Thermo-Sensitive Gel for Rats with Grade III Pancreatic Trauma.

Background/aims: This study investigated the protection provided by gabexate mesylate thermo-sensitive gel (GMTI) against grade III pancreatic trauma in rats.

Methods: A grade III pancreatic trauma model with main pancreatic duct dividing was established, and the pancreas anatomical diagram, ascites, and serum biochemical indices, including amylase, lipase, C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were examined. The pancreas was sliced and stained with hematoxylin eosin and subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.

Thermal and magnetic dual-responsive liposomes with a cell-penetrating peptide-siRNA conjugate for enhanced and targeted cancer therapy.

Due to the absence of effective in vivo delivery systems, the employment of small interfering RNA (siRNA) in the clinic has been hindered. Here, we describe a novel siRNA targeting system that combines features of biological (cell-permeable peptides, CPPs) and physical (magnetic) siRNA targeting for use in magnetic hyperthermia-triggered release. A siRNA-CPPs conjugate (siRNA-CPPs) was loaded into thermal and magnetic dual-responsive liposomes (TML) (siRNA-CPPs/TML), and in vitro siRNA-CPPs thermosensitive release activity, targeted cellular uptake, gene silencing efficiency, in vivo targeted delivery and in vivo antitumor activity were determined.

Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability.

Oxaliplatin (OXP) was reported to show low anti-tumor activity when used alone and to display side effects; this low activity was attributed to high partitioning to erythrocytes and low accumulation in tumors. Thermosensitive liposomes (TSL) were considered able to specifically deliver drugs to heated tumors and to resolve the OXP distribution problem. Regretfully, TSL encapsulating doxorubicin did not demonstrate significant improvement in progression-free survival.

Thermo-Sensitive Liposome co-Loaded of Vincristine and Doxorubicin Based on Their Similar Physicochemical Properties had Synergism on Tumor Treatment.

Purpose: To develop vincristine (VCR) and doxorubicin (DOX) co-encapsulated thermo-sensitive liposomes (VD-TSL) against drug resistance, with increased tumor inhibition rate and decreased system toxicity, improving drug targeting efficiency upon mild hyperthermia (HT) in solid tumor.

Methods: Based on similar physicochemical properties, VCR and DOX were co-loaded in TSL with pH gradient active loading method and characterized. The time-dependent drug release profiles at 37 and 42°C were assessed by HPLC.

Synchronous delivery of felodipine and metoprolol tartrate using monolithic osmotic pump technology.

The synchronous sustained-release of two drugs was desired urgently for patients needing combination therapy in long term. However, sophisticated technologies were used generally to realize the simultaneous delivery of two drugs especially those with different physico-chemical properties. The purpose of this study was to obtain the concurrent release of felodipine and metoprolol tartrate, two drugs with completely different solubilities, in a simple monolithic osmotic pump system (FMOP).

Polymer Nanoparticles Modified with Photo- and pH-Dual-Responsive Polypeptides for Enhanced and Targeted Cancer Therapy.

The cationic nature of cell penetrating peptides (CPPs) and their absence of cell selectivity restrains their applications in vivo. In this work, polymer nanoparticles (NPs) modified with photo- and pH-responsive polypeptides (PPPs) were successfully developed and respond to near-infrared (NIR) light illumination at the tumor site and a lowered tumor extracellular pH (pHe). In PPPs, the internalization function of CPPs (positively charged) is quenched by a pH-sensitive inhibitory peptide (negatively charged), which is linked via a photocleavable group.

Does Thermosensitive Liposomal Vinorelbine Improve End-Point Survival after Percutaneous Radiofrequency Ablation of Liver Tumors in a Mouse Model?

Purpose To investigate the role of thermosensitive liposome-encapsulated vinorelbine (Thermo-Vin) in combined radiofrequency (RF) ablation of liver tumors. Materials and Methods Approval from the institutional animal care and use committee was obtained before this study. First, the anticancer efficacy of Thermo-Vin was assessed in vitro (H22 cells) for 72 hours at 37°C or 42°C.