title: Nanoconjugate Platforms Development Based in Poly(β,L-Malic Acid) Methyl Esters for Tumor Drug Delivery.
abstract: New copolyesters derived from poly(β,L-malic acid) have been designed to serve as nanoconjugate platforms in drug delivery. 25% and 50% methylated derivatives (coPMLA-Me(25)H(75) and coPMLA-Me(50)H(50)) with absolute molecular weights of 32 600 Da and 33 100 Da, hydrodynamic diameters of 3.0 nm and 5.2 nm and zeta potential of -15mV and -8.25mV, respectively, were found to destabilize membranes of liposomes at pH 5.0 and pH 7.5 at concentrations above 0.05mg/mL. The copolymers were soluble in PBS (half life of 40 hours) and in human plasma (half life of 15 hours) but they showed tendency to aggregate at high levels of methylation. Fluorescence-labeled copolymers were internalized into MDA-MB-231 breast cancer cells with increased efficiency for the higher methylated copolymer. Viability of cultured brain and breast cancer cell lines indicated moderate toxicity that increased with methylation. The conclusion of the present work is that partially methylated poly(β,L-malic acid) copolyesters are suitable as nanoconjugate platforms for drug delivery.
authors.affiliation: Department of Neurosurgery, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8631 W. Third Street, Suite 800E, Los Angeles, CA 90048, USA.
authors.forename: José
authors.initials: J
authors.lastname: Portilla-Arias
authors.forename: Rameshwar
authors.initials: R
authors.lastname: Patil
authors.forename: Jinwei
authors.initials: J
authors.lastname: Hu
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.forename: Keith L
authors.initials: KL
authors.lastname: Black
authors.forename: Montserrat
authors.initials: M
authors.lastname: García-Alvarez
authors.forename: Sebastián
authors.initials: S
authors.lastname: Muñoz-Guerra
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Ljubimova
authors.forename: Eggehard
authors.initials: E
authors.lastname: Holler