Efficient delivery of the Bcl-2 antisense oligonucleotide G3139 via nucleus-targeted aCD33-NKSN nanoparticles.

G3139 is an antisense oligodeoxyribonucleotide (ODN) developed as a Bcl-2 down-regulating agent for the treatment of acute myelogenous leukemia (AML). However, the clinical efficacy of G3139 has been shown to be limited due to its rapid plasma clearance and low permeability. To enhance the effective delivery of G3139, this work prepared a novel nano gene delivery vector (aCD33-NKSN) consisting of a CD33 antigbody (aCD33), a nuclear localization signal (NLS), gene fusion peptides (KALA), and stearic acid (SA) for CD33 antigen targeting and nuclear localization.

Design of a Novel Nucleus-Targeted NLS-KALA-SA Nanocarrier to Delivery Poorly Water-Soluble Anti-Tumor Drug for Lung Cancer Treatment.

In this study, we designed a novel nucleus-targeted nanocarrier (NLS-KALA-SA, NKSN) consisting of Kala peptide (KALA), nuclear localization signal (NLS) and stearic acid (SA) using Fmoc solid phase synthesis method. We chose Curcumin (CUR), Paclitaxel (PTX), Ginsenoside compound K(CK) as models of poorly water-soluble antitumor drugs, The drugs loaded NLS-KALA-SA nanoparticles (CUR/NKSN, PTX/NKSN, CK/NKSN) were obained by the dialysis method, their physicochemical properties were determined and antitumor activity were evaluated. The NLS-KALA-SA nanoparticles were spherical shaped with an average size of 76.

Photoluminescent functionalized carbon quantum dots loaded electroactive Silk fibroin/PLA nanofibrous bioactive scaffolds for cardiac tissue engineering.

Tissue engineering and stem cell rehabilitation are the hopeful aspects that are being investigated for the management of Myocardial Infarction (MI); cardiac patches have been used to start myocardial rejuvenation. In this study, we engineered p-phenylenediamine surface functionalized (modif-CQD) into the Silk fibroin/PLA (SF/PLA) nanofibrous bioactive scaffolds with improved physico-chemical abilities, mechanical and cytocompatibility to cardiomyocytes. The micrograph results visualized the morphological improved spherical modif-CQD have been equivalently spread throughout the SF/PLA bioactive cardiac scaffolds.

The inhibiting role of hydroxypropylmethylcellulose acetate succinate on piperine crystallization to enhance its dissolution from its amorphous solid dispersion and permeability.

The purpose of this study was to demonstrate that inhibiting crystallization by HPMCAS played a key role in enhancing dissolution and absorption of piperine (Pip) from its amorphous solid dispersion (ASD). Nucleation induction time and supersaturation tests were used to evaluate the ability of the polymers to inhibit crystallization of Pip. The prepared solid dispersions were characterized by DSC and FTIR.

Caproyl-Modified G2 PAMAM Dendrimer (G2-AC) Nanocomplexes Increases the Pulmonary Absorption of Insulin.

We aimed to investigate the absorption-enhancing effect (AEE) of caproyl-modified G2 PAMAM dendrimer (G2-AC) on peptide and protein drugs via the pulmonary route. In this study, G2 PAMAM dendrimer conjugates modified with caproic acid was synthesized, the pulmonary absorption of insulin as models with or without G2-AC were evaluated. The results indicated that G2-AC6 exhibited a greatest AEE for insulin in various caproylation levels of G2-AC.

Age-related and gender-stratified differences in the association between high triglyceride and risk of hyperuricemia.

Background: Elevated serum uric acid is commonly associated with high triglyceride. However, the relation of triglyceride and hyperuricemia in different gender and age groups is currently not well understood. This study aimed to evaluate age- and gender-related association of high triglyceride with hyperuricemia in a subgroup of Chinese population.

5β-Cholanic Acid/Glycol Chitosan Self-Assembled Nanoparticles (5β-CHA/GC-NPs) for Enhancing the Absorption of FDs and Insulin by Rat Intestinal Membranes.

The absorption-enhancing effects of glycol chitosan modified by 5β-cholanic acid nanoparticles (5β-CHA/GC-NPs) on a drug with poor absorption in the intestine were studied by the method of in situ closed loop. We chose fluorescein isothiocyanate-labeled dextrans (FDs) and insulin as the model drugs. 5β-CHA/GC-NPs loaded to different drugs were prepared by the dialysis method, and the physicochemical characteristics and in vitro release profiles of nanoparticles were also estimated.

LncRNA ENST00113 promotes proliferation, survival, and migration by activating PI3K/Akt/mTOR signaling pathway in atherosclerosis.

Background: Atherosclerosis is one of the most common cardiovascular disorders. The dysfunction of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are 2 key factors in the formation of atherosclerosis. This study aims to find strategies to prevent VSMCs and ECs dysfunction for the treatment of atherosclerosis.

Tat-Tagged and Folate-Modified N-Succinyl-chitosan (Tat-Suc-FA) Self-assembly Nanoparticle for Therapeutic Delivery OGX-011 to A549 Cells.

The objective of this study was to develop a novel type of an antisense oligonucleotide (OGX-011) loaded Tat-tagged and folate-modified N-succinyl-chitosan (Tat-Suc-FA) nanoparticles (NPs) for improving tumor targetability. In this study, Tat-Suc-FA/OGX-011NPs were prepared and its physicochemical characterizations were also evaluated. The nanoparticles showed an average diameter of 73 ± 16.

Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat.

In search of an effective and less toxic absorption enhancer, we synthesized primary amine acetylation of generation 2 polyamidoamine (G2 PAMAM) dendrimer (Ac-G2) by the reaction of G2 PAMAM dendrimer with acetic anhydride, and evaluated the effects of Ac-G2 on the intestinal absorption of poorly absorbable water-soluble drugs using an in situ closed-loop method in rats. The results indicated that Ac50-G2 had a greatest absorption enhancing effect for 5(6)-carboxyfluorescein (CF) in various acetylation levels of G2 PAMAM dendrimers. Ac50-G2 with various concentrations (0.

Lipid Nanoparticles Loaded with an Antisense Oligonucleotide Gapmer Against Bcl-2 for Treatment of Lung Cancer.

Purpose: Bcl-2 is an anti-apoptotic gene that is frequently overexpressed in human cancers. G3139 is an antisense oligonucleotide against bcl-2 that has shown limited efficacy in clinical trials. Here, we report the synthesis of a new antisense oligonucleotide containing additional chemical modifications and its delivery using nanoparticles.

Circulating miR-122-5p as a potential novel biomarker for diagnosis of acute myocardial infarction.

Background: MicroRNAs (miRNAs) play key roles in cardiac development, and the expression of miRNAs is altered in the diseased heart. The aim of this study was to explore the value of circulating microRNA-122-5p (miR-122-5p) as a potential biomarker for acute myocardial infarction (AMI).

Methods: Plasma samples from 50 patients with AMI and 39 healthy adults (non-AMI controls) were collected.

Synthesis of Tat tagged and folate modified N-succinyl-chitosan self-assembly nanoparticles as a novel gene vector.

The purpose of this research was to prepare a novel type of Tat tagged and folate modified N-succinyl-chitosan (Tat-Suc-FA) self-assembly nanoparticles, to provide a new vector for tumor gene therapy. In this study, Tat-Suc-FA polymers was synthesized and characterized using (1)H NMR and FT-IR. The copolymer had a mean diameter of 65 ± 22.

Improved tumor targetability of Tat-conjugated PAMAM dendrimers as a novel nanosized anti-tumor drug carrier.

The generation 4-poly-amidoamine-dendrimers (PAMAM G4 dendrimer, P) was conjugated to Tat peptide (Tat, T), a cell-penetrating peptide, in search of an efficient anti-tumor drug delivery vehicle for cancer therapy. In this study, we synthesized BODIPY-labeled Tat-Conjugated PAMAM dendrimers (BPTs) as a novel nanosized anticancer drug carriers and systemically investigated their biodistribution and the tumor accumulation in Sarcoma 180-bearing mice. In addition, the uptake and the cytotoxicity to S180 cells of BPTs thereof were evaluated.

In vivo biodistribution for tumor targeting of 5-fluorouracil (5-FU) loaded N-succinyl-chitosan (Suc-Chi) nanoparticles.

5-Fluorouracil-loaded N-succinyl-chitosan nanoparticles (5-FU-Suc-Chi/NP) were prepared by emulsification solvent diffusion. Biodistribution and tumor targeting were evaluated after i.v.

Preparation of N-succinyl-chitosan and its physical-chemical properties as a novel excipient.

The aim of this work is to prepare N-succinyl-chitosan (Suc-Chi) and measure physical-chemical properties for Suc-Chi as excipients. Suc-Chi were prepared via ring-opening reactions with succinic anhydride in Dimethyl Sulfoxide system. The physical-chemical properties of Suc-Chi, such as the degree of substitution (DS), solubility, isoelectric point (pI), glass transition temperature (Tg), partition coefficient (P(app)) and zata potential were detected respectively in order to evaluate their possibility as drug carriers.

Nanoparticles of 5-fluorouracil (5-FU) loaded N-succinyl-chitosan (Suc-Chi) for cancer chemotherapy: preparation, characterization--in-vitro drug release and anti-tumour activity.

N-Succinyl-chitosan has favourable properties as a drug carrier, such as biocompatibility, low toxicity and long-term retention in the body. It is a good candidate for cancer chemotherapy as a polymeric drug carrier. This study describes the preparation and characterization of 5-fluorouracil-loaded N-succinyl-chitosan nanoparticles (5-FU-Suc-Chi/NP) by an emulsification solvent diffusion method.