Interlaboratory Reproducibility of Standardized Hemagglutination Inhibition Assays.

The hemagglutination inhibition (HI) assay is a prominent and commonly accepted method used to determine quantitative antibody titers for influenza virus. However, the reproducibility and consistency of this assay may be affected by several factors, including its reliance on biological reagents that are difficult to standardize, such as red blood cells. This report assesses HI assay performance across three accredited, global laboratories when using test virus and a human serum panel aliquoted and distributed from a centrally located reagent stock.

A Phase I/II Trial of BNC105P with Everolimus in Metastatic Renal Cell Carcinoma.

Purpose: BNC105P inhibits tubulin polymerization, and preclinical studies suggest possible synergy with everolimus. In this phase I/II study, efficacy and safety of the combination were explored in patients with metastatic renal cell carcinoma (mRCC).

Experimental Design: A phase I study in patients with clear cell mRCC and any prior number of therapies was conducted using a classical 3 + 3 design to evaluate standard doses of everolimus with increasing doses of BNC105P.

A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma.

BNC105P is a tubulin polymerisation inhibitor that selectively disrupts tumour vasculature and suppresses cancer cell proliferation. This agent has exhibited preclinical and phase I activity in Malignant Pleural Mesothelioma (MPM). This phase II, single arm trial investigated the efficacy and safety of BNC105P as second line therapy in MPM.

Clinical, pharmacodynamic, and pharmacokinetic evaluation of BNC105P: a phase I trial of a novel vascular disrupting agent and inhibitor of cancer cell proliferation.

Purpose: To determine the recommended phase II dose and evaluate the safety and toxicity profile and pharmacokinetic (PK) and pharmacodynamic (PD) effects of BNC105P, an inhibitor of tubulin polymerization that has vascular disrupting and antiproliferative effects.

Experimental Design: BNC105P was administered as a 10-minute infusion on days 1 and 8 of a 21-day cycle in a first-in-human phase I study. A dynamic accelerated dose titration method was used for dose escalation.

Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice.

We report the biodistribution and pharmacokinetics (PK) of a cyclic RGD-doxorubicin-nanoparticle (NP) formulation in tumor-bearing mice. The NP core was composed of inulin multi-methacrylate with a targeting peptide, cyclic RGD, covalently attached to the NPs via PEG-400. Seventy-two percent of the doxorubicin was attached to the NP matrix via an amide bond; 28% of doxorubicin was entrapped as unconjugated drug.

In vitro study of GDNF release from biodegradable PLGA microspheres.

Glial cell line-derived neurotrophic factor (GDNF) is a protein with potent trophic actions on dopaminergic neurons, which is under investigation as a therapeutic agent for the treatment of neurodegenerative disorders, including Parkinson's disease. The aim of this work was to develop GDNF-loaded microspheres, which could be implanted by stereotaxy in the brain and could offer an alternative strategy in the treatment of Parkinson's disease. A w/o/w extraction-evaporation technique was chosen to prepare protein-loaded microspheres.

Encapsulation of protamine sulphate compacted DNA in polylactide and polylactide-co-glycolide microparticles.

This paper details the development and characterisation of a DNA-loaded microsphere system for gene delivery purposes. Encapsulation of DNA in microspheres was carried out by precondensation of the DNA with protamine sulphate, followed by encapsulation in a polymeric microsphere using a water-oil-water (w/o/w) solvent evaporation-emulsion process. The polymers used were polylactide and polylactide-co-glycolide.

A novel in vitro delivery system for assessing the biological integrity of protein upon release from PLGA microspheres.

Purpose: The development of a novel in vitro system is required to assess the stability and release kinetics of a protein microsphere formulation used for drug delivery to the brain.

Methods: Microspheres containing lysozyme as model protein were prepared using a (w/o/w) emulsion-solvent evaporation process. Both the active and total (active + inactive) encapsulation efficiencies and release profiles were determined.