RETRACTED: Self-assembled phenylalanine-α,β-dehydrophenylalanine nanotubes for sustained intravitreal delivery of a multi-targeted tyrosine kinase inhibitor (Retracted article. See vol. 237, pg. 186, 2016)

Current standard of care for sustained back of the eye drug delivery is surgical placement or injection of large, slow release implants using a relatively large 22 gauge needle. We designed novel dipeptide (phenylalanine-alpha,beta,dehydrophenylalanine; Phe-Delta Phe) based nanotubes with a diameter of similar to 15-30 nm and a length of similar to 1500 nm that could be injected with a 33 gauge needle for sustained intravitreal delivery of pazopanib, a multi targeted tyrosine kinase inhibitor. The drug could be loaded during nanotube assembly or post loaded after nanotube formation, with the former being more efficient at 25% w/w pazopanib loading and similar to 55% loading efficiency. Plain and peptide loaded nanotube were non-cytoloxic to retinal pigment epithelial cells even at a concentration of 200 mu g/ml. Following intravitreal injection of fluorescently labeled nanotubes using a 33 gauge needle in a rat model, the nanotube persistence and drug delivery were monitored using noninvasive fluorophotometry, electron microscopy and mass spectrometry analysis. Nanotubes persisted in the vitreous humor during the 15 days study and pazopanib levels in the vitreous humor, retina, and choroid-RPE at the end of the study were 4.5, 5, and 2.5-folds higher, respectively, compared to the plain drug. Thus, Phe-Delta Phe nanotubes allow intravitreal injections with a small gauge needle and sustain drug delivery. (C) 2013 Elsevier B.V. All rights reserved,