title: Injectable, in situ forming poly(propylene fumarate)-based ocular drug delivery systems.
abstract: This study sought to develop an injectable formulation for long-term ocular delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug and the biodegradable polymer poly(propylene fumarate) (PPF) in the biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon injection of the solution into an aqueous environment, a FA-loaded PPF matrix is precipitated in situ through the diffusion/extraction of NMP into surrounding aqueous fluids. Fabrication of the matrices and in vitro release studies were performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5% were achieved. High performance liquid chromatography was employed to determine the released amount of FA. The effects of drug loading, PPF content of the injectable formulation, and additional photo-crosslinking of the matrix surface were investigated. Overall, FA release was sustained in vitro over up to 400 days. After an initial burst release of 22 to 68% of initial FA loading, controlled drug release driven by diffusion and bulk erosion was observed. Drug release rates in a therapeutic range were demonstrated. Release kinetics were found to be dependent on drug loading, formulation PPF content, and extent of surface crosslinking. The results suggest that injectable, in situ formed PPF matrices are promising candidates for the formulation of long-term, controlled delivery devices for intraocular drug delivery.
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas 77251-1892, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ueda
authors.forename: M C
authors.initials: MC
authors.lastname: Hacker
authors.forename: A
authors.initials: A
authors.lastname: Haesslein
authors.forename: S
authors.initials: S
authors.lastname: Jo
authors.forename: D M
authors.initials: DM
authors.lastname: Ammon
authors.forename: R N
authors.initials: RN
authors.lastname: Borazjani
authors.forename: J F
authors.initials: JF
authors.lastname: Kunzler
authors.forename: J C
authors.initials: JC
authors.lastname: Salamone
authors.forename: A G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry; D005123:Eye; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives* / Q000737:chemistry; D005650:Fumarates / Q000737:chemistry*; D005938:Glucocorticoids / Q000737:chemistry*; D007700:Kinetics; D011126:Polypropylenes / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D005650:Fumarates; D005938:Glucocorticoids; D011126:Polypropylenes; D011760:Pyrrolidinones; C097850:poly(propylene fumarate); D005446:Fluocinolone Acetonide; C035394:fluocinolone; C038678:N-methylpyrrolidone