An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake.

Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs.

Detection of Peptide-based nanoparticles in blood plasma by ELISA.

Aims: The aim of the current study was to develop a method to detect peptide-linked nanoparticles in blood plasma.

Materials & Methods: A convenient enzyme linked immunosorbent assay (ELISA) was developed for the detection of peptides functionalized with biotin and fluorescein groups. As a proof of principle, polymerized pentafluorophenyl methacrylate nanoparticles linked to biotin-carboxyfluorescein labeled peptides were intravenously injected in Wistar rats.

Design and physicochemical characterization of poly(amidoamine) nanoparticles and the toxicological evaluation in human endothelial cells: applications to peptide delivery to the brain.

In this study, we investigated nanoparticles formulated by self-assembly of a biodegradable poly(amidoamine) (PAA) and a fluorescently labeled peptide, in their capacity to internalize in endothelial cells and deliver the peptide, with possible applications for brain drug delivery. The nanoparticles were characterized in terms of size, surface charge, and loading efficiency, and were applied on human cerebral microvascular endothelial cells (hCMEC/D3) and human umbilical vein endothelial cells (Huvec) cells. Cell-internalization and cytotoxicity experiments showed that the PAA-based nanocomplexes were essentially nontoxic, and the peptide was successfully internalized into cells.

Headspace-SPME-GC/MS as a simple cleanup tool for sensitive 2,6-diisopropylphenol analysis from lipid emulsions and adaptable to other matrices.

Due to increased regulatory requirements, the interaction of active pharmaceutical ingredients with various surfaces and solutions during production and storage is gaining interest in the pharmaceutical research field, in particular with respect to development of new formulations, new packaging material and the evaluation of cleaning processes. Experimental adsorption/absorption studies as well as the study of cleaning processes require sophisticated analytical methods with high sensitivity for the drug of interest. In the case of 2,6-diisopropylphenol - a small lipophilic drug which is typically formulated as lipid emulsion for intravenous injection - a highly sensitive method in the concentration range of μg/l suitable to be applied to a variety of different sample matrices including lipid emulsions is needed.

Rapid online-SPE-MS/MS method for ketoprofen determination in dermal interstitial fluid samples from rats obtained by microdialysis or open-flow microperfusion.

Pharmacokinetic studies of topical ketoprofen formulations using continuous sampling techniques such as microdialysis (MD) or open-flow microperfusion (OFM) require sensitive assays due to small sample volumes. A simple and easy online-SPE-MS/MS method for ketoprofen analysis was developed for both MD and OFM samples obtained from rat dermal tissue. The quantification range is 25-5000 ng/ml with a limit of detection of 3 ng/ml using only 10 microl sample volume.