Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection.
Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5 mg/ml and 10 mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.
a Department of Ophthalmology , The Second Xiangya Hospital, Central South University , Changsha , Hunan , China .|b Department of Ophthalmology , University of Tennessee Health Science Center , Memphis , TN , USA .
Huiling
H
Li
b Department of Ophthalmology , University of Tennessee Health Science Center , Memphis , TN , USA .
Mallika
M
Palamoor
b Department of Ophthalmology , University of Tennessee Health Science Center , Memphis , TN , USA .|c Department of Anatomy and Neurobiology , University of Tennessee Health Science Center , Memphis , TN , USA , and.|d Department of Pharmaceutical Sciences , University of Tennessee Health Science Center , Memphis , TN , USA.
Monica M
MM
Jablonski
D000818:Animals; D003257:Consumer Product Safety; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D016503:Drug Delivery Systems; D004596:Electroretinography; D005123:Eye / Q000187:drug effects* / Q000378:metabolism; D005128:Eye Diseases / Q000188:drug therapy; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects; D058449:Intravitreal Injections; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D011817:Rabbits; D013499:Surface Properties; D014018:Tissue Distribution; D041623:Tomography, Optical Coherence
D004337:Drug Carriers; D011108:Polymers; C401107:poly(ortho ester)
Chronic intraocular diseases; intraocular delivery; localization; poly(ortho ester) nanoparticles; safety