Tuesday, September 9, 2014

New Publication utilizes Mal-PEG-PLGA (Polyvivo AI20) and polyaspartic acid to form bone-tissue targeted nanoparticle

PolySciTech (www.polyscitech.com) provides an array of block copolymers as well as reactive intermediates including polyvivo AI20. Recently researchers utilized PolyVivo AI20 (Mal-PEG-PLGA) along with mPEG-PLGA from PolySciTech to generate a nanoparticle sytem which they then conjugated to thiol endcapped polyaspartic acid to form a targeted system for bone-tissue targeting.  This system was validated against osteoblast cells/stem cells as well as ex-vivo tibia sections to show that it provided a non-cytotoxic method for specifically targeting bone tissue.  This method could be used to aid delivery of drugs specifically to bone tissue for treatment of bone diseases. Read more: Jiang, Tao, Xiaohua Yu, Erica J. Carbone, Clarke Nelson, Ho Man Kan, and Kevin W-H. Lo. "Poly aspartic acid peptide-linked PLGA based nanoscale particles: Potential for bone-targeting drug delivery applications." International Journal of Pharmaceutics (2014). http://www.sciencedirect.com/science/article/pii/S0378517314006334

“Abstract: Delivering drugs specifically to bone tissue is very challenging due to the architecture and structure of bone tissue. Poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) hold great promise for the delivery of therapeutics to bone tissue. The goal of the present research was to formulate a PLGA-based NP drug delivery system for bone tissue exclusively. Since poly-aspartic acids (poly-Asp) peptide sequence has been shown to bind to hydroxyapatite (HA), and has been suggested as a molecular tool for bone-targeting applications, we fabricated PLGA-based NPs linked with poly-Asp peptide sequence. Nanoparticles made of methoxy – poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged poly-Asp peptide was conjugated to the surface of the nanoparticles via the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the Cdouble bond; length as m-dashC double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged poly-Asp peptide to PLGA NPs was confirmed by NMR analysis and fluorescent microscopy. The developed nanoparticle system is highly aqueous dispersible with an average particle size of ∼80 nm. In vitro binding analyses demonstrated that FITC-poly-Asp NPs were able to bind to HA gel as well as to mineralized matrices produced by human mesenchymal stem cells and mouse bone marrow stromal cells. Using a confocal microscopy technique, an ex vivo binding study of mouse major organ ground sections revealed that the FITC-poly-Asp NPs were able to bind specifically to the bone tissue. In addition, proliferation studies indicated that our FITC-poly-Asp NPs did not induce cytotoxicity to human osteoblast-like MG63 cell lines. Altogether, these promising results indicated that this nanoscale targeting system was able to bind to bone tissue specifically and might have a great potential for bone disease therapy in clinical applications. Keywords: Nanoparticles; Targeted drug delivery; Peptides; Bone diseases”


No comments: