One-year chronic toxicity evaluation of single dose intravenously administered silica nanoparticles in mice and their Ex vivo human hemocompatibility.

Chronic toxicity evaluations of nanotechnology-based drugs are essential to support initiation of clinical trials. Ideally such evaluations should address the dosing strategy in human applications and provide sufficient information for long-term usage. Herein, we investigated one-year toxicity of non-surface modified silica nanoparticles (SNPs) with variations in size and porosity (Stöber SNPs 46 ± 4.

Subchronic and chronic toxicity evaluation of inorganic nanoparticles for delivery applications.

Inorganic nanoparticles provide the opportunity to localize bioactive agents to the target sites and protect them from degradation. In many cases, acute toxicities of inorganic nanoparticles used for delivery applications have been investigated. However, little information is available regarding the long-term toxicity of such materials.

Subchronic toxicity of silica nanoparticles as a function of size and porosity.

Despite increasing reports of using silica nanoparticles (SNPs) for controlled drug delivery applications, their long-term toxicity profile following intravenous administration remains unexplored. Herein, we investigated the acute (10-day) and subchronic (60-day and 180-day) toxicity of nonporous SNPs of approximately 50 nm (Stöber SNPs50) and approximately 500 nm in diameter (Stöber SNPs500), and mesoporous SNPs of approximately 500 nm in diameter (MSNPs500) upon single-dose intravenous injection into male and female immune-competent inbred BALB/c mice. The Maximum Tolerated Dose (MTD) of the particles was determined 10 days post-injection.

In vitro synergistic action of geldanamycin- and docetaxel-containing HPMA copolymer-RGDfK conjugates against ovarian cancer.

HPMA copolymer-RGDfK (HPMA-RGDfK) conjugates bearing either aminohexylgeldanamycin (AHGDM) or docetaxel (DOC) were synthesized and characterized. In vitro stability and binding were evaluated. Cytotoxicity toward ovarian cancer cells was evaluated and the ability of the conjugates to induce cell death was assessed by combination index analysis.

Biodegradable multiblock poly(N-2-hydroxypropyl)methacrylamide gemcitabine and paclitaxel conjugates for ovarian cancer cell combination treatment.

The synthesis, characterization, and in vitro evaluation of a combination delivery of multiblock poly(N-2-hydroxypropyl)methacrylamide (HPMA), gemcitabine (GEM) and paclitaxel (PTX) conjugates is described in this study. Multiblock copolymer conjugates of a large molecular weight (Mw>200 kDa) were studied and compared to traditional, small molecular weight (Mw<45 kDa) conjugates. Stability of the conjugates in different pH was assessed, and their cytotoxicity in combination toward A2780 human ovarian cancer cells was evaluated by combination index analysis.