Non-viral systemic delivery of siRNA or antisense oligonucleotides targeted to Jun N-terminal kinase 1 prevents cellular hypoxic damage.

Many pathological conditions and environmental impacts lead to the development of severe tissue hypoxia that aggravates the primary disorder, provokes cell death, and limits the patient's recovery. We hypothesized that suppression of Jun N-terminal kinase 1 (JNK1) will limit tissue damage induced by severe hypoxia. To test the hypothesis, antisense oligonucleotides (ASO) or small interfering RNA (siRNA) targeted to JNK1 mRNA were incorporated or complexed with neutral or cationic liposomes, respectively, and administered systemically to mice prior to hypoxia exposure.

Intratracheal versus intravenous liposomal delivery of siRNA, antisense oligonucleotides and anticancer drug.

Purpose: To compare systemic intravenous and local intratracheal delivery of doxorubicin (DOX), antisense oligonucleotides (ASO) and small interfering RNA (siRNA).

Methods: "Neutral" and cationic liposomes were used to deliver DOX, ASO, and siRNA. Liposomes were characterized by dynamic light scattering, zeta-potential, and atomic force microscopy.

Surface-modified and internally cationic polyamidoamine dendrimers for efficient siRNA delivery.

A novel internally quaternized and surface-acetylated poly(amidoamine) generation four dendrimer (QPAMAM-NHAc) was synthesized and evaluated for intracellular delivery of siRNA. The proposed dendrimer as a nanocarrier possesses the following advantages: (1) modified neutral surface of the dendrimer for low cytotoxicity and enhanced cellular internalization; (2) existence of cationic charges inside the dendrimer (not on the outer surface) resulting in highly organized compact nanoparticles, which can potentially protect nucleic acids from degradation. The properties of this dendrimer were compared with PAMAM-NH 2 dendrimer, possessing surface charges, and with an internally quaternized charged and hydroxyl-terminated QPAMAM-OH dendrimer.

JNK1 as a molecular target to limit cellular mortality under hypoxia.

Many pathological conditions and environmental impacts lead to a decrease in tissue oxygen supply and severe cellular hypoxia. This secondary hypoxia can disturb cellular homeostasis, limiting the efficacy of the prescribed treatment for the primary lesion, eventually leading to cellular and organismal death. Jun N-terminal kinase 1 (JNK1) plays a major role in the hypoxic cellular damage.

Use of 2,2'-azobis(2-amidinopropane) dihydrochloride as a reagent tool for evaluation of oxidative stability of drugs.

Purpose: To study the oxidative degradation of drugs using a hydrophilic free radical initiator, 2,2'-Azobis(-amidinopropane) dihydrochloride (AAPH).

Methods: AAPH was used as the free radical initiator to study oxidation of three model compounds (A, B, and C), which represent different oxidizable moieties. In the solution model, the drugs and AAPH were dissolved in a mixture of acetonitrile and aqueous buffer and incubated at elevated temperatures to evaluate oxidative degradation.

Molecular weight and degree of deacetylation effects on lipase-loaded chitosan bead characteristics.

The effects of the molecular weight (MW) and degree of deacetylation (DD) of chitosan on chitosan hydrogel beads were characterized, and the entrapment efficiency, release of entrapped lipase, and activity of immobilized Candida rugosa lipase were investigated. Fresh and freeze-dried beads were characterized. A solution of lipase was prepared in a 1.

Immobilization of lipase using hydrophilic polymers in the form of hydrogel beads.

The purpose of this study was to immobilize lipase (triacylglycerol ester hydrolase, E.C. 3.