Nose-to-brain drug delivery system with ligand/cell-penetrating peptide-modified polymeric nano-micelles for intracerebral gliomas.

We previously developed a nose-to-brain delivery system using poly(ethylene glycol)-polycaprolactone block polymeric micelles modified by a cell-penetrating peptide, Tat (PEG-PCL-Tat). This system showed excellent delivery of the anti-cancer drug camptothecin to the brain and improved therapeutic efficacy in a brain tumor model. However, improvements are necessary to selectively deliver drugs to tumor sites once they enter the brain, and avoid toxic side effects to normal brain tissue.

Fundamental evaluation and optimization of porous spherical silica for developing functional fine particles via fluidized bed coating.

Particle coating, a taste-masking technique for drugs, is limited by its long manufacturing time, which is caused by the decrease in the spray rate required to prevent particle agglomeration. Mesoporous silica particles, which have a high surface area and pore sizes in the range of 2-50 nm, possess high surface free energy; they have attracted significant interest for numerous applications in adsorption, separation, and catalysis and drug delivery. A form of mesoporous silica, microbead silicate, can prevent particle aggregation because of its good water absorbency and drying properties.

Intranasal delivery of camptothecin-loaded tat-modified nanomicells for treatment of intracranial brain tumors.

The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials.

Cell-penetrating peptide-modified block copolymer micelles promote direct brain delivery via intranasal administration.

Purpose: In order to develop non-invasive and effective nose-to-brain delivery of drugs, we synthesized Tat analog-modified methoxy poly(ethylene glycol) (MPEG)/poly(ε-caprolactone) (PCL) amphiphilic block copolymers through the ester bond.

Methods: We evaluated the brain distribution of coumarin, acting as a model chemical, after intravenous or intranasal administration of MPEG-PCL. In addition, cellular uptake of coumarin by rat glioma cells transfected with coumarin-loaded MPEG-PCL or MPEG-PCL-Tat was determined.