Extended intravitreal rabbit eye residence of nanoparticles conjugated with cationic arginine peptides for intraocular drug delivery: In vivo imaging

Ignacio Melgar-Asensio, Irawati Kandela, Fraser Aird, Soesiawati R. Darjatmoko, Cristobal de los Rios, Christine M. Sorenson, Daniel M. Albert, Nader Sheibani, Jack Henkin

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

PURPOSE. Drug delivery by intravitreal injection remains problematic, small agents and macromolecules both clearing rapidly. Typical carriers use microparticles (>2 μm), with size-related liabilities, to slow diffusion. We recently described cationic nanoparticles (NP) where conjugated Arg peptides prolonged residence in rat eyes, through ionic interaction with vitreal poly-anions. Here we extended this strategy to in vivo tracking of NP-conjugate (NPC) clearance from rabbit eyes. Relating t 1/2 to zeta potential, and varied dose, we estimated the limits of this charge-based delivery system. METHODS. NPC carried covalently attached PEG 8 -2Arg or PEG 8 -3Arg pentapeptides, having known sequences from human eye proteins. Peptides were conjugated (61–64 per NPC); each NP/NPC also carried a cyanine7 tag (<0.5 dye/particle). In vivo imaging system (IVIS), after intravitreal injection, estimated NPC loss by 800-nm photon emission (745-nm excitation) at 1 to 3-week intervals following initial scan at day 10. RESULTS. NPC of 2Arg-peptides or 3Arg-peptides showed clearance t 1/2 of 7 days and 17 days respectively, unconjugated NP t 1/2 was <<5 days. Doses of 90, 180, and 360 μg of PEG 8 -2Arg NPC were compared. The lower doses showed dose-proportional day-10 concentration, and similar clearance. Higher early loss was seen with a 360-μg dose, exceeding rabbit vitreal binding capacity. No inflammation was observed. CONCLUSIONS. This type of cationic NPC can safely increase residence t 1/2 in a 1 to 3-week range, with dose <100 μg per mL vitreous. Human drug load may then range from 10 to 100 μg/eye, usefulness depending on individual drug potency and release rate, superimposed on extended intravitreal residence.

Original languageEnglish (US)
Pages (from-to)4071-4081
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number10
DOIs
StatePublished - Aug 2018

Keywords

  • Cationic peptides
  • Hyaluronic acid
  • Intravitreal drug delivery
  • Nanoparticles
  • Rabbit eye imaging

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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