RESUMO
The vitreous humor is the first barrier encountered by intravitreally injected nanoparticles. Lipid-based nanoparticles in the vitreous are studied by evaluating their diffusion with single-particle tracking technology and by characterizing their protein coronae with surface plasmon resonance and high-resolution proteomics. Single-particle tracking results indicate that the vitreal mobility of the formulations is dependent on their charge. Anionic and neutral formulations are mobile, whereas larger (>200 nm) neutral particles have restricted diffusion, and cationic particles are immobilized in the vitreous. PEGylation increases the mobility of cationic and larger neutral formulations but does not affect anionic and smaller neutral particles. Convection has a significant role in the pharmacokinetics of nanoparticles, whereas diffusion drives the transport of antibodies. Surface plasmon resonance studies determine that the vitreal corona of anionic formulations is sparse. Proteomics data reveals 76 differentially abundant proteins, whose enrichment is specific to either the hard or the soft corona. PEGylation does not affect protein enrichment. This suggests that protein-specific rather than formulation-specific factors are drivers of protein adsorption on nanoparticles in the vitreous. In summary, our findings contribute to understanding the pharmacokinetics of nanoparticles in the vitreous and help advance the development of nanoparticle-based treatments for eye diseases.
Assuntos
Nanopartículas/química , Soluções Oftálmicas/administração & dosagem , Doenças Retinianas/tratamento farmacológico , Corpo Vítreo/metabolismo , Adsorção , Animais , Difusão , Composição de Medicamentos/métodos , Humanos , Injeções Intravítreas , Lipossomos , Soluções Oftálmicas/farmacocinética , Tamanho da Partícula , Polietilenoglicóis/química , Coroa de Proteína/análise , Coroa de Proteína/metabolismo , Proteômica , Propriedades de Superfície , Sus scrofaRESUMO
Exudative age-related macular degeneration, characterized by choroidal neovascularization (CNV), is a major cause of visual loss. In this study, we examined the distribution of the polyion complex (PIC) micelle encapsulating FITC-P(Lys) in blood and in experimental CNV in rats to investigate whether PIC micelle can be used for treatment of CNV. We demonstrate that PIC micelle has long-circulating characteristics, accumulating to the CNV lesions and is retained in the lesion for as long as 168 h after intravenous administration. These results raise the possibility that PIC micelles can be used for achieving effective drug targeting to CNV.
Assuntos
Corioide/irrigação sanguínea , Neovascularização de Coroide/patologia , Animais , Corioide/patologia , Modelos Animais de Doenças , Degeneração Macular/patologia , Masculino , Micelas , Ratos , Ratos Endogâmicos BN , Retina/patologiaRESUMO
Photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD) was evaluated using a supramolecular nanomedical device, that is, a novel dendritic photosensitizer (DP) encapsulated by a polymeric micelle formulation. The characteristic dendritic structure of the DP prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. With its highly selective accumulation on choroidal neovascularization (CNV) lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity.