The peptide lycosin-I attenuates TNF-α-induced inflammation in human umbilical vein endothelial cells via IκB/NF-κB signaling pathway.

Objective: The peptide lycosin-I has anti-bacterial and anti-cancer capacities. However, the anti-inflammatory activity of lycosin-I remains unknown. We investigated whether lycosin-I could attenuate inflammation.

mPEG- b-PLGA/PCL/MCT Mixed Micelles as Carriers of Disulfiram for Improving Plasma Stability and Antitumor Effect in Vivo.

The clinical application of disulfiram (DSF) in cancer treatments is hindered by its rapid degradation in the blood circulation. In this study, methoxy poly(ethylene glycol)- b-poly(lactide- co-glycolide)/poly(ε-caprolactone) (mPEG- b-PLGA/PCL) micelles were developed for encapsulation of DSF by using the emulsification-solvent diffusion method. Medium chain triglyceride (MCT) was incorporated into the mixed polymeric micelles to improve drug loading by reducing the core crystallinity.

Tablets of paliperidone using compression-coated technology for controlled ascending release.

The aim of this work was to prepare ascending release compression-coated (CC) tablets with paliperidone (PAL) using a simple manufacturing technique and short manufacturing process. The release behavior and mechanisms of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose (HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose (HPMC-K100M).

Intestinal Mucin Induces More Endocytosis but Less Transcytosis of Nanoparticles across Enterocytes by Triggering Nanoclustering and Strengthening the Retrograde Pathway.

Mucus, which is secreted by the goblet cells of enterocytes, constitutes the first obstacle encountered for the intestinal absorption of nanomedicines. For decades, mucus has simply been regarded as a physical barrier that hinders the permeation and absorption of drugs, because of its high viscosity and reticular structure, whereas the interaction of mucus ingredients with nanomedicines is usually neglected. It is unclear whether glycoproteins, as the main components of mucus, interact with nanomedicines.

Core/shell PLGA microspheres with controllable in vivo release profile via rational core phase design.

Highly soluble drugs tend to release from preparations at high speeds, which make them need to be taken at frequent intervals. Additionally, some drugs need to be controlled to release in vivo at certain periods, so as to achieve therapeutic effects. Thus, the objective of this study is to design injectable microparticulate systems with controllable in vivo release profile.

Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection.

Purpose: To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo.

Methods: PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated.

pH-sensitive polymeric nanoparticles of mPEG-PLGA-PGlu with hybrid core for simultaneous encapsulation of curcumin and doxorubicin to kill the heterogeneous tumour cells in breast cancer.

Most breast tumours are heterogeneous and not only contain the bulk of differentiated tumour cells but also a small population of highly tumorigenic and intrinsically drug-resistant cancer stem cells (CSCs). Herein, a pH-sensitive nanoparticle with simultaneous encapsulation of curcumin and doxorubicin (CURDOX-NPs) was prepared by using monomethoxy (polyethylene glycol)-b-P (D,L-lactic-co-glycolic acid)-b-P (L-glutamic acid) polymer to simultaneously target the differentiated tumor cells and CSCs. CURDOX-NPs had a mean diameter of 107.

Vasodilator and hypotensive effects of the spider peptide Lycosin-I in vitro and in vivo.

Lycosin-I, a spider peptide isolated from the venom of the spider Lycosa singoriensis, has anti-bacteria and anti-cancer properties in organisms. However, cardiovascular effects of Lycosin-I have not been studied. In this study, we investigated for the first time the vasodilator and hypotensive effects of Lycosin-I and the possible mechanisms, in order to develop a promising treatment for hypertension-related diseases.

Targeting ALDH2 with disulfiram/copper reverses the resistance of cancer cells to microtubule inhibitors.

Disulfiram (DSF) in combination with copper (Cu) has been reported to override drug resistance in cancer cells, and DSF combined with chemotherapy based on the microtubule inhibitor vinorelbine appears to prolong survival in non-small cell lung cancer patients. Here, we investigated the mechanisms underlying these findings. DSF/Cu reversed the microtubule inhibitor resistance in A549/Taxol and KB/VCR cells in vitro, and had anti-tumor effects in A549/Taxol and KB/VCR xenograft mice.

Enhanced oral absorption and anticancer efficacy of cabazitaxel by overcoming intestinal mucus and epithelium barriers using surface polyethylene oxide (PEO) decorated positively charged polymer-lipid hybrid nanoparticles.

Polymer-lipid hybrid nanoparticles, PMONPs, were developed to improve the oral absorption of cabazitaxel (CTX), a semi-synthetic taxane derivative, by overcoming multiple gastrointestinal barriers. The nano-carrier is comprised of a poly(ε-caprolactone) (PCL) and chain triglyceride (MCT) hybrid core for drug loading, and a positively charged surface while slightly concealed with a polyethylene oxide (PEO) shell by insertion of poloxamer 188, with the aim of improving the intestinal mucus permeation and epithelial cell uptake. The CTX-loaded PMONPs (CTX-PMONPs) were optimized with 10% MCT content in the core, and characterization showed they were on the nanoscale with a size of 170.

Pharmacokinetics of a ternary conjugate based pH-responsive 10-HCPT prodrug nano-micelle delivery system.

A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT.

Formulation and Pharmacokinetics of HSA-core and PLGA-shell Nanoparticles for Delivering Gemcitabine.

Gemcitabine-loaded core-shell nanoparticles (CSNPs), comprised of a cross-linked HSA-core and PLGA-shell, were prepared through a modified double emulsification method, and the processing parameters were systematically investigated. The optimized CSNPs had a particle size of 241 ± 36.2 nm and an encapsulation efficiency of 41.

Vincristine-loaded liposomes prepared by ion-paring techniques: Effect of lipid, pH and antioxidant on chemical stability.

In the present study, vincristine (VCR)-loaded liposomes were designed by ion-pairing techniques and the model could be applied to investigate the effect of lipids on the degradation of vinca alkaloids, and how to weaken their influence by adjusting pH and adding antioxidants. It was found that there was a positive correlation between degree of degradation and the unsaturation extent of the phospholipids. In the phospholipid with the lowest oxidation index, only 6% of VCR was degraded in 6days at 37°C, whereas for the phospholipids with highest oxidation index, the degradation reached above 95% over the same time.

Improving Tumor Specificity and Anticancer Activity of Dasatinib by Dual-Targeted Polymeric Micelles.

To improve tumor targetability and drug efficacy and decrease drug resistance of dasatinib (DSB), the multifunctional micellar nanoparticles that combined the matrix metalloproteinase 2 (MMP2)-sensitive tumor (site) targeting with folate receptor-mediated tumor (cell) targeting were developed. Two major functional polymers, polyethylene glycol (5000 Da)-MMP2-sensitive peptide-phosphoethanolamine (PEG5k-pp-PE) and folic acid-polyethylene glycol (2000 Da)-phosphoethanolamine (FA-PEG2k-PE), were synthesized to construct the dual-targeted micellar nanoparticles (MMP/FR micelles). In the absence of MMP2, the FA was shielded by PEG5k and the MMP/FR micelles showed low bioactivity.

In Vitro-In Vivo Relationship of Amorphous Insoluble API (Progesterone) in PLGA Microspheres.

Purpose: The mechanism of PRG release from PLGA microspheres was studied and the correlation of in vitro and in vivo analyses was assessed.

Methods: PRG-loaded microspheres were prepared by the emulsion-evaporate method. The physical state of PRG and microstructure changings during the drug release period were evaluated by powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) respectively.

Polyester-Solid Lipid Mixed Nanoparticles with Improved Stability in Gastro-Intestinal Tract Facilitated Oral Delivery of Larotaxel.

The objective of this study was to investigate the role of core stability of nanoparticles on their performances in oral drug delivery. Solid lipids (Geleol Mono and Diglycerides Nf) were incorporated into nanoparticles composed of mPEG-b-PCL by the dialysis method. The prepared solid lipid loaded nanoparticles were found to be spherical nanoparticles with a core state and size distribution dependent on the amount of solid lipid incorporated.

A parenteral docetaxel-loaded lipid microsphere with decreased 7-epidocetaxel conversion in vitro and in vivo.

The purpose of the study was to develop a parenteral docetaxel lipid microsphere to inhibit its 7-epidocetaxel conversion in vitro and in vivo. 7-epidocetaxel conversion as the main indicator was investigated to optimize the formulation and process. 10% medium-chain triglyceride/long-chain triglyceride (3:1) as the oil phase, egg lecithin E80 as the emulsifier and 0.

Poly(vinyl methyl ether/maleic anhydride)-Doped PEG-PLA Nanoparticles for Oral Paclitaxel Delivery To Improve Bioadhesive Efficiency.

Bioadhesive nanoparticles based on poly(vinyl methyl ether/maleic anhydride) (PVMMA) and poly(ethylene glycol) methyl ether-b-poly(d,l-lactic acid) (mPEG-b-PLA) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4.

Scale-up cultivation enhanced arachidonic acid accumulation by red microalgae Porphyridium purpureum.

The present study attempts to cultivate Porphyridium purpureum under different scale-up conditions for further development and commercialization of microalgae-derived PUFAs such as ARA and EPA. Different temperatures (25, 30, and 35 °C) and light intensities (70, 165, and 280 μmol/ms) were applied to the 50 L pilot-scale cultivation of P. purpureum in ASW.

Improved tumor tissue penetration and tumor cell uptake achieved by delayed charge reversal nanoparticles.

Unlabelled: The high affinity of positively charged nanoparticles to biological interfaces makes them easily taken up by tumor cells but limits their tumor permeation due to non-specific electrostatic interactions. In this study, polyion complex coated nanoparticles with different charge reversal profiles were developed to study the influence of charge reversal profile on tumor penetration. The system was constructed by polyion complex coating using micelles composed of poly (lysine)-b-polycaprolactone (PLys-b-PCL) as the cationic core and poly (glutamic acid)-g- methoxyl poly (ethylene glycol) (PGlu-g-mPEG) as the anionic coating material.

Injectable Sustained-Release Depots of PLGA Microspheres for Insoluble Drugs Prepared by hot-Melt Extrusion.

Purpose: Progesterone (PRG) was selected as a model drug to develop a long-acting injection system for poorly water-soluble drugs.

Methods: Microspheres with high density-low porosity were prepared by hot-melt extrusion (HME) combined with wet-milling as the representative formulation, and a microcrystal suspension was also studied as a comparison. The morphology, particle size and distribution, polymorphism, drug distribution, density and porosity were characterized by scanning electron microscopy, laser diffraction particle size analyzer, power X-ray diffraction and DSC respectively.

Cooking with Active Oxygen and Solid Alkali: A Promising Alternative Approach for Lignocellulosic Biorefineries.

Lignocellulosic biomass, a matrix of biopolymers including cellulose, hemicellulose, and lignin, has gathered increasing attention in recent years for the production of chemicals, fuels, and materials through biorefinery processes owing to its renewability and availability. The fractionation of lignocellulose is considered to be the fundamental step to establish an economical and sustainable lignocellulosic biorefinery. In this Minireview, we summarize a newly developed oxygen delignification for lignocellulose fractionation called cooking with active oxygen and solid alkali (CAOSA), which can fractionate lignocellulose into its constituents and maintain its processable form.

5-Aminolevulinic acid promotes arachidonic acid biosynthesis in the red microalga .

Background: The microalga within Rhodophyta abundantly produces several valuable proteins, polysaccharides, pigments and long-chain polyunsaturated fatty acid; it is especially effective in accumulating arachidonic acid (ARA). However, this high ARA yield is always achieved in conditions unfavourable for cell growth. In this study, we present a method for obtaining desirable ARA levels from while simultaneously promoting cell growth using appropriate concentrations of the growth hormone 5-Aminolevulinic acid (5-ALA).

Exenatide-loaded microsphere/thermosensitive hydrogel long-acting delivery system with high drug bioactivity.

A series of mixed hydrogels of PLGA-PEG-PLGA and PCLA-PEG-PCLA were synthesized, and investigated in terms of their critical micelle concentration, stability and thermosensitive properties. Also, some mixed hydrogel was selected to prepare Depot-gel-in-Ms-in-Matrix-gel system for the treatment of type 2 diabetes mellitus. Briefly, Exenatide (EXT) loaded hydrogels was encapsulated in PLGA microspheres (Ms) and further encapsulated into blank hydrogel.

Discovery of Stromal Regulatory Networks that Suppress Ras-Sensitized Epithelial Cell Proliferation.

Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation.