Polymeric nano-micelles as novel tools for LY2157299 cancer cells delivery

Background:One of the cell signaling pathway antagonistagainst TGFbis LY2157299 (LY) (Lilly): a very small moleculehaving high tumor diffusion. LY dosage can be diluted by bloodplasma, engulfed by immune system or it might be lost duringdigestion in gastrointestinal tract. Our aim is to optimize anano-biomechanical vehicle to avoid acidic pH of gastrointesti-nal tract, colon alkaline pH and anti-immune recognition. Poly-galacturonic acid (PgA) is a not degradable in thegastrointestinal tract due to its insolubility at acidic pH. Strategyof this study is to avoid PgA solubility in colon by Polyacrylicacid (PAA) complementation.Materials and Methods:Fluorescence of Rhodamine 6G (R6G)-labeled PgA was investigated by fluorescence spectrophotome-try. Polymeric micelles formed by Polyethylene glycol-folic acidcovering PgA-PAA were investigated by Transmission ElectronMicorscopy (TEM) and Atomic Force Microscopy (AFM) . Effi-ciency and loading capacity of LY engulfed inside nano-micelleswere measured by mass spectrometry and confocal microscopyrespectively.Results:PgA and PAA have extendable and shrinkablemechanical properties in alkaline and acidic pH. Fluorescencespectrophotometry confirms successful labeling of PgA byR6G. Interconnection of PgA-PAA alkaline group surfacewas reveled by using zeta potential. Polymeric micelles arespherical, head-tail connected and have soft structures witha diameter ranging from 50-100 nm. Mass spectrometry con-firms that micelles have good capacity of encapsulating LY.Confocal microscopy shows efficiency of LY-loaded micellesactivity.Conclusions:Mechanical properties of PgA-PAA micelles havestrengthened their potential use for oral and injected dosage.PEG-FA increases the time dose circulation in blood streamand their selective target. Interconnection of PgA-PAA enhancesLY capacity due to amino-carboxylic (PgA-PAA) groups.