Extended Intravitreal Rabbit Eye Residence of Nanoparticles Conjugated With Cationic Arginine Peptides for Intraocular Drug Delivery: In Vivo Imaging.
Invest Ophthalmol Vis Sci
; 59(10): 4071-4081, 2018 08 01.
Article
em En
| MEDLINE
| ID: mdl-30098194
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 t1/2 to zeta potential, and varied dose, we estimated the limits of this charge-based delivery system.Methods:
NPC carried covalently attached PEG8-2Arg or PEG8-3Arg 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 t1/2 of 7 days and 17 days respectively, unconjugated NP t1/2 was <<5 days. Doses of 90, 180, and 360 µg of PEG8-2Arg 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 t1/2 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Arginina
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Corpo Vítreo
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Portadores de Fármacos
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Sistemas de Liberação de Medicamentos
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Nanopartículas
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Injeções Intravítreas
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article