Simultaneously Inhibiting P-gp Efflux and Drug Recrystallization Enhanced the Oral Bioavailability of Nintedanib.

Introduction: Nintedanib (NDNB) is a novel triple-angiokinase inhibitor for the treatment of lung cancer. However, the oral bioavailability of NDNB is only 4.7% owing to the poor solubility and the efflux of P-glycoprotein (P-gp).

Preparation, Characterization and Evaluation of Long-Acting Rivaroxaban-Loaded Microspheres.

Background: Rivaroxaban is widely used for long-term prevention and maintenance therapy of thromboembolic disorders. The existing oral dosage forms of rivaroxaban lead to poor patient adherence because of repeated daily administration. The aim of this study is to design long-acting rivaroxaban- loaded microspheres to reduce dosing frequency and improve patient compliance.

Bile acid transporter mediated STC/Soluplus self-assembled hybrid nanoparticles for enhancing the oral drug bioavailability.

The nano-particulate system for oral delivery faces a big challenge across the gastrointestinal bio-barriers. The aim was to explore the potential applications of bile acid transporter mediated the self-assembled hybrid nanoparticles (SHNPs) of sodium taurocholate (STC) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) for augmenting the oral delivery of poorly water-soluble drugs. Felodipine (FLDP) was chosen as a model drug.

Magnetic Reactive Oxygen Species Nanoreactor for Switchable Magnetic Resonance Imaging Guided Cancer Therapy Based on pH-Sensitive FeC@FeO Nanoparticles.

Reactive oxygen species (ROS) are crucial molecules in cancer therapy. Unfortunately, the therapeutic efficiency of ROS is unsatisfactory in clinic, primarily due to their rigorous production conditions. By taking advantage of the intrinsic acidity and overproduction of HO in the tumor environment, we have reported an ROS nanoreactor based on core-shell-structured iron carbide (FeC@FeO) nanoparticles (NPs) through the catalysis of the Fenton reaction.

Novel Hot Melt Extruded Matrices of Hydroxypropyl Cellulose and Amorphous Felodipine-Plasticized Hydroxypropyl Methylcellulose as Controlled Release Systems.

Hydroxypropyl methylcellulose (HPMC) is a hydrophilic retarding-release polymer with the limited application in hot melt extrusion (HME) due to its high glass transition temperature (T 181-191°C) and melt viscosity. The aim of this study is to develop hot melt extruded matrices using hydroxypropyl cellulose (HPC) and felodipine (FLDP) with HPMC for controlled release and explore the relations of their specialty, processability, and structure with the product properties. Results showed that FLDP/HPC/HPMC can be extruded at 160°C with torques not more than 0.

Bottom-Up and Top-Down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates.

The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.

The Synergetic Effects of Nonpolar and Polar Protic Solvents on the Properties of Felodipine and Soluplus in Solutions, Casting Films, and Spray-Dried Solid Dispersions.

The aim was to explore the effects of nonpolar and polar protic solvents composed of dichloromethane (DCM) and ethanol (EtOH) on the properties of felodipine (FLDP) and Soluplus in solutions, casting films, and spray-dried drug-rich or polymer-rich solid dispersions (SDs). Measurement of intrinsic viscosity and solubility indicated that FLDP and Soluplus were miscible. EtOH-DCM ranging from 20:80 to 50:50 induced the strongest molecular interactions for FLDP-Soluplus-solvents systems.

Novel self-assembled tacrolimus nanoparticles cross-linking thermosensitive hydrogels for local rheumatoid arthritis therapy.

The aim was to explore the potential application of novel self-assembled nanoparticles cross-linking thermosensitive hydrogels composed of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) and tacrolimus (FK-506) for local therapy of rheumatoid arthritis (RA). The sol-gel transition temperature (T), gelation time, rheological behaviors, in vitro release, in vivo gelation and retention, and therapeutic efficacy against adjuvant-induced arthritis (AIA) rats were compared between the Soluplus hydrogels and widely studied poloxamer 407 (P407) delivery systems. In sol, the spherical and uniform FK506 loaded Soluplus nanoparticles (Soluplus-SNPs) were self-assembled with encapsulation efficiency of 99.

Optimization of a cationic liposome-based gene delivery system for the application of miR-145 in anticancer therapeutics.

In order to improve the delivery efficiency of microRNA (miRNA or miR)-145, the present study examined several factors which may affect cationic liposome (CL)-based transfection, including the hydration medium used for the preparation of liposomes, the quantity of the plasmid, the molar ratio of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP)/cholesterol (chol), or DOTAP/chol, and the weight ratio of DOTAP/DNA. In order to enhance the transfection efficiency, protamine was selected as a DNA-condensing agent to form liposome‑protamine‑DNA (LPD) ternary complexes. An agarose gel retardation assay was used to examine the DNA binding affinity of the CLs.

Liposomal oxymatrine in hepatic fibrosis treatment: formulation, in vitro and in vivo assessment.

The aim was to develop a liposomal oxymatrine conjugating D-alpha tocopheryl polyethylene glycol 1000 succinate (OMT-LIP) for enhanced therapeutics of hepatic fibrosis. OMT-LIP was prepared using the remote loading method. The influences of formulation compositions on the encapsulation efficiency of OMT-LIP were investigated.

Formulation, antileukemia mechanism, pharmacokinetics, and biodistribution of a novel liposomal emodin.

Emodin is a multifunctional Chinese traditional medicine with poor water solubility. D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a pegylated vitamin E derivate. In this study, a novel liposomal-emodin-conjugating TPGS was formulated and compared with methoxypolyethyleneglycol 2000-derivatized distearoyl-phosphatidylethanolamine (mPEG2000-DSPE) liposomal emodin.

Preparation, therapeutic efficacy and intratumoral localization of targeted daunorubicin liposomes conjugating folate-PEG-CHEMS.

Folate polyethylene glycol-cholesterol hemisuccinate (folate-PEG-CHEMS) is a novel folate ligand firstly synthesized by our group and demonstrated good stability and potential targeting results on KB cells in vitro. The current study further explored endocytosis mechanisms of liposomes via folate receptor on L1210JF cells and assessed targeted therapeutic efficacy of folate-PEG-CHEMS anchored liposomes loading daunorubicin (F-L-DNR) in vivo. Folate-PEG-CHEMS was synthesized by a modified method.

Triggering liposomal drug release with a lysosomotropic agent.

Drug release from liposomes in the endosome-lysosomal organelles into cytoplasm is critical to cytotoxicity and anticancer effects. Chloroquine is a lysosomotropic agent that has been reported to enhance in vitro cytotoxicity of basic anticancer drugs. To investigate the mechanism of chloroquine triggering basic anticancer drugs release from liposomes and the potential to treat solid tumors in clinic, daunorubicin was loaded into folate-targeted liposomes by ammonium sulfate remote loading method.

[Inhibitive effect of local perfusion of tanshinone II A nanoparticles on MMP-2 secretion].

Objective: To test the effect of Tanshinone II A nanoparticles on the expression of MMP-2.

Methods: Thirty five male New Zealand white rabbits were randomly divided into three groups. In group A (15 rabbits), the carotid arteries of the rabbits were stripped.

[The inhibitive effect produced by local perfusion of tanshinone IIA nanoparticle on neointimal hyperplasia of rabbit carotid artery following intimal denudation].

Tanshinone IIA nanoparticles were constructed and perfused in rabbit's right carotid after intimal denudation with ballon. Localization and retention at different time points of the coumarin-labeled drug nanoparticles were evaluated under laser confocal microscope. Nanoparticles were seen in the three layers of the cross-section artery.

Solid lipid nanoparticles of mitoxantrone for local injection against breast cancer and its lymph node metastases.

In an attempt to improve the therapeutic effect of mitoxantrone (MTO) against breast cancer and its lymph node metastases, solid lipid nanoparticles (SLN) of MTO were prepared, characterized and evaluated on mice. Film dispersion-ultrasonication method was used to prepare MTO-SLN, optimized by central composite design. MTO-SLN were prepared with a mean size of 61 nm, drug content (DC) of 4.

Mitoxantrone-loaded BSA nanospheres and chitosan nanospheres for local injection against breast cancer and its lymph node metastases. I: Formulation and in vitro characterization.

Positively charged mitoxantrone (MTO) was absorbed by negatively charged blank bovine serum albumin (BSA) and chitosan (CS) nanospheres to form MTO-BSA-NS and MTO-CS-NS, respectively. In addition to other conditions, values of pH of every step were optimized. On optimized conditions, MTO-BSA-NS of a mean size of 77 nm with an encapsulation yield (EY) of (98.

Mitoxantrone-loaded BSA nanospheres and chitosan nanospheres for local injection against breast cancer and its lymph node metastases. II: Tissue distribution and pharmacodynamics.

Bovine serum albumin (BSA) and chitosan (CS) nanospheres of mitoxantrone (MTO) were comparatively evaluated in terms of tissue distribution, acute toxicity and therapeutic efficiency against breast cancer and its lymph node metastases. After local injection in rats, MTO nanospheres showed a slower elimination rate and a much higher drug concentration in lymph nodes compared with MTO solution, and a lower drug concentration in other tissues. There was no observed acute toxicity to the main tissues of Kunming mice after local injection of MTO-BSA-NS.