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.
The control of biodegradation and the improvement of moldability of poly-L-lactide, PLA, have been difficult because of the high crystallinity and the lability of melt viscosity. The synthesis of biodegradable PLA having the branched structure, comb-type PLA, was carried out by using only metabolizable materials to obtain a new material showing the controlled degradation and good molding properties, and to provide information on correlation of branched structure with biodegradability. A depsipeptide-lactide random copolymer having pendant hydroxy groups, poly[(Glc-Ser)-LA], was obtained by ring-opening copolymerization of L-lactide, LA, with a protected cyclodepsipeptide, cyclo[Glc-Ser(OBzl)], and consequent deprotection. The obtained copolymer was used as a macroinitiator for graft-polymerization of LA to give comb-type PLA. The obtained comb-type PLA showed a lower glass transition point, melting point, and apparent crystallinity than linear PLA. Furthermore, it was suggested that the degradation rate of comb-type PLA could be adjusted by controlling the molecular architecture such as molecular weight of main chain and/or side chain and number of graft chain.
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.
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