The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection

Koo, Heebeom; Moon, Hyungwon; Han, Hyounkoo; Na, Jin Hee; Huh, Myung Sook; Park, Jae Hyung; Woo, Se Joon; Park, Kyu Hyung; Kwon, Ick Chan; Kim, Kwangmeyung; Kim, Hyuncheol

doi:10.1016/j.biomaterials.2012.01.030

Cited by 175 publications

(136 citation statements)

References 24 publications

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“…Furthermore, this suggests that intravitreally delivered material can reach the subretinal space, even if it is not efficiently taken up/expressed by photoreceptors, a phenomenon that has been seen previously with various other types of NPs. 26,27 Given this observation, and the importance of intravitreal delivery, our future studies will likely focus on optimizing this approach along with enhancing photoreceptor uptake.…”

Section: Discussionmentioning

confidence: 99%

DNA nanoparticles are safe and nontoxic in non-human primate eyes

Kelley

Conley

Makkia

et al. 2018

IJN

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Introduction DNA nanoparticles (NPs) comprising polylysine conjugated to polyethylene glycol efficiently target murine photoreceptors and the retinal pigment epithelium (RPE) and lead to long-term phenotypic improvement in models of retinal degeneration. Advancing this technology requires testing in a large animal model, particularly with regard to safety. So, herein we evaluate NPs in non-human primates (baboon). Methods and results NPs with plasmids carrying GFP and a ubiquitous, RPE-specific, or photoreceptor-specific promoter were delivered by either subretinal or intravitreal injection. We detected GFP message and protein in the retina/RPE from eyes dosed with NPs carrying ubiquitously expressed and RPE-specific vectors, and GFP message in eyes injected with NPs carrying photoreceptor-specific vectors. Importantly, we observed NP DNA in the retina/RPE following intravitreal injection, indicating the inner limiting membrane does not prevent NP diffusion into the outer retina. We did not observe any adverse events in any baboon, and there were no NP-associated changes in retinal function. Furthermore, no systemic or local inflammatory reaction to the vectors/injections was observed, and no NP DNA was found outside the eye. Conclusion Taken together with the well-established rodent safety and efficacy data, these findings suggest that DNA NPs may be a safe and potentially clinically viable nonviral ocular therapy platform for retinal diseases.

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Section: Discussionmentioning

confidence: 99%

DNA nanoparticles are safe and nontoxic in non-human primate eyes

Kelley

Conley

Makkia

et al. 2018

IJN

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“…Therefore, scientists (Amrite et al, 2008;Huu et al, 2015) concluded that the nanoparticle that is not easy to be cleared by blood and lymph circulation is an ideal choice to achieve carrying drugs from sclera to posterior segment of eyes. After administrate HA nanoparticle in eyes by intravitreal injection, the nanoparticle can penetrate the whole retina and locate in the retinal pigment epithelium of normal retina (Kim et al, 2009;Koo et al, 2012). It can also reach the choroid.…”

Section: Hyaluronic Acidmentioning

confidence: 99%

Advance of the application of nano-controlled release system in ophthalmic drug delivery

Wang

Zhang

2015

Drug Delivery

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“…Among all types of visual impairment, 80% are treatable or can be avoided through healthy diet and lifestyle [43]. While some ocular disorders can be treated with laser surgeries, topical drug administration, transscleral delivery, or intravitreal injection, the application of nanoparticle systems for diagnosis and treatment of these afflictions has the potential to improve efficacy, biocompatibility, and targeting of APIs [44]. The most effective conventional treatment for agerelated macular degeneration, ischemic retinal vein occlusions, or diabetic retinopathy is intravitreal injection of anti-vascular-endothelial-growth-factor (anti-VEGF), which combats abnormal angiogenesis [3,44].…”

Section: Nanoparticles Of 5β-cholanic Acidmodified Glycol Chitosan Anmentioning

confidence: 99%

“…The ability of nanoparticles to distribute throughout the retina, based on their surface properties, was studied by Koo et al [44]. The various nanoparticles, including those of GC (18, Figure 6) and hyaluronic acid (HA), were injected into the vitreous humor of rats, and the distribution was characterized by confocal laser scanning microscopy and TEM.…”

Section: Nanoparticles Of 5β-cholanic Acidmodified Glycol Chitosan Anmentioning

confidence: 99%

“…They were able to penetrate the vitreal barrier but not the inner limiting membrane, which is the first layer of the retina. In contrast, particles composed of the anionic polymers, HA and HSA, were able to distribute throughout the retina, reaching the retinal pigment epithelium [44]. Such nanoparticles could potentially be used as drug or gene carriers for treating retinal and optic nerve disorders such as glaucoma, age-related macular degeneration, and diabetic retinopathy.…”

Section: Nanoparticles Of 5β-cholanic Acidmodified Glycol Chitosan Anmentioning

confidence: 99%

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Self-assembled polysaccharide nanostructures for controlled-release applications

Myrick

Vendra

Krishnan

2014

Nanotechnology Reviews

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Self-assembling polysaccharide nanostructures have moved to the forefront of many fields due to their wide range of functional properties and unique advantages, including biocompatability and stimulus responsiveness. In particular, the field of controlled release, which involves influencing the location, concentration, and efficacy of active pharmaceutical ingredients (APIs), diagnostics, nutrients, or other bioactive compounds, has benefited from polysaccharide biomaterials. Nanostructure formation, stimulus responsiveness, and controlledrelease performance can be engineered through facile chemical functionalization and noncovalent intermolecular interactions. This review discusses polysaccharide nanoparticles, designed for targeted and time-controlled delivery of emerging APIs, with improved in vivo retention, stability, solubility, and permeability characteristics. Topics covered include nanoparticles of cyclodextrin and cyclodextrin-containing polymers, hydrophobically modified polysaccharides, polysaccharide nanoparticles that respond to pH, temperature, or light stimulus, polysaccharide prodrug complexes, polysaccharide complexes with lipids and proteins, and other polysaccharide polyelectrolyte complexes.

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The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection

Cited by 175 publications

References 24 publications

DNA nanoparticles are safe and nontoxic in non-human primate eyes

DNA nanoparticles are safe and nontoxic in non-human primate eyes

Advance of the application of nano-controlled release system in ophthalmic drug delivery

Self-assembled polysaccharide nanostructures for controlled-release applications

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