Hanieh Safari1, Reheman Adili2, Michael Holinstat3, Omolola Eniola-Adefeso4. 1. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, United States. 2. Department of pharmacology, University of Michigan, Ann Arbor, MI 48019, United States. 3. Department of pharmacology, University of Michigan, Ann Arbor, MI 48019, United States; Department of Cardiovascular Medicine, Samuel and Jean Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI 48109, United States. 4. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, United States; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, United States; Macromolecular Science and Engineering Program, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: lolaa@umich.edu.
Abstract
HYPOTHESIS: Though the emulsion solvent evaporation (ESE) technique has been previously modified to produce rod-shaped particles, it cannot generate small-sized rods for drug delivery applications due to the inherent coupling and contradicting requirements for the formation versus stretching of droplets. The separation of the droplet formation from the stretching step should enable the creation of submicron droplets that are then stretched in the second stage by manipulation of the system viscosity along with the surface-active molecule and oil-phase solvent. EXPERIMENTS: A two-step ESE protocol is evaluated where oil droplets are formed at low viscosity followed by a step increase in the aqueous phase viscosity to stretch droplets. Different surface-active molecules and oil phase solvents were evaluated to optimize the yield of biodegradable PLGA rods. Rods were assessed for drug loading via an imaging agent and vascular-targeted delivery application via blood flow adhesion assays. FINDINGS: The two-step ESE method generated PLGA rods with major and minor axis down to 3.2 µm and 700 nm, respectively. Chloroform and sodium metaphosphate was the optimal solvent and surface-active molecule, respectively, for submicron rod fabrication. Rods demonstrated faster release of Nile Red compared to spheres and successfully targeted an inflamed endothelium under shear flow in vitro and in vivo.
HYPOTHESIS: Though the emulsion solvent evaporation (ESE) technique has been previously modified to produce rod-shaped particles, it cannot generate small-sized rods for drug delivery applications due to the inherent coupling and contradicting requirements for the formation versus stretching of droplets. The separation of the droplet formation from the stretching step should enable the creation of submicron droplets that are then stretched in the second stage by manipulation of the system viscosity along with the surface-active molecule and oil-phase solvent. EXPERIMENTS: A two-step ESE protocol is evaluated where oil droplets are formed at low viscosity followed by a step increase in the aqueous phase viscosity to stretch droplets. Different surface-active molecules and oil phase solvents were evaluated to optimize the yield of biodegradable PLGA rods. Rods were assessed for drug loading via an imaging agent and vascular-targeted delivery application via blood flow adhesion assays. FINDINGS: The two-step ESE method generated PLGA rods with major and minor axis down to 3.2 µm and 700 nm, respectively. Chloroform and sodium metaphosphate was the optimal solvent and surface-active molecule, respectively, for submicron rod fabrication. Rods demonstrated faster release of Nile Red compared to spheres and successfully targeted an inflamed endothelium under shear flow in vitro and in vivo.
Authors: Yan Geng; Paul Dalhaimer; Shenshen Cai; Richard Tsai; Manorama Tewari; Tamara Minko; Dennis E Discher Journal: Nat Nanotechnol Date: 2007-03-25 Impact factor: 39.213
Authors: Margaret B Fish; Catherine A Fromen; Genesis Lopez-Cazares; Alexander W Golinski; Timothy F Scott; Reheman Adili; Michael Holinstat; Omolola Eniola-Adefeso Journal: Biomaterials Date: 2017-02-04 Impact factor: 12.479
Authors: Hanieh Safari; Nicholas Kaczorowski; Michael L Felder; Emma R Brannon; Mita Varghese; Kanakadurga Singer; Omolola Eniola-Adefeso Journal: Sci Adv Date: 2020-12-04 Impact factor: 14.136