title: Nanoliposomal minocycline for ocular drug delivery.
abstract: Nanoliposomal technology is a promising drug delivery system that could be employed to improve the pharmacokinetic properties of clearance and distribution in ocular drug delivery to the retina. We developed a nanoscale version of an anionic, cholesterol-fusing liposome that can encapsulate therapeutic levels of minocycline capable of drug delivery. We demonstrate that size extrusion followed by size-exclusion chromatography can form a stable 80-nm liposome that encapsulates minocycline at a concentration of 450 ± 30 μM, which is 2% to 3% of loading material. More importantly, these nontoxic nanoliposomes can then deliver 40% of encapsulated minocycline to the retina after a subconjunctival injection in the STZ model of diabetes. Efficacy of therapeutic drug delivery was assessed via transcriptomic and proteomic biomarker panels. For both the free minocycline and encapsulated minocycline treatments, proinflammatory markers of diabetes were downregulated at both the messenger RNA and protein levels, validating the utility of biomarker panels for the assessment of ocular drug delivery vehicles.
  
  
  BACKGROUND
  Authors developed a nano-liposome that can encapsulate minocycline for optimized intraocular drug delivery. These nontoxic nanoliposomes delivered 40% of encapsulated minocycline to the retina after a subconjunctival injection in a diabetes model.
authors.affiliation: Department of Pharmacology, Pennsylvania State College of Medicine, Hummelstown, PA 17036, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Kaiser
authors.forename: Hisanori
authors.initials: H
authors.lastname: Imai
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Haakenson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brucklacher
authors.forename: Todd E
authors.initials: TE
authors.lastname: Fox
authors.forename: Sriram S
authors.initials: SS
authors.lastname: Shanmugavelandy
authors.forename: Kellee A
authors.initials: KA
authors.lastname: Unrath
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Pedersen
authors.forename: Pingqi
authors.initials: P
authors.lastname: Dai
authors.forename: Willard M
authors.initials: WM
authors.lastname: Freeman
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Bronson
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gardner
authors.forename: Mark
authors.initials: M
authors.lastname: Kester
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D008081:Liposomes; D008911:Minocycline / Q000008:administration & dosage*; D036103:Nanotechnology; D016133:Polymerase Chain Reaction; D051381:Rats
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D008911:Minocycline