Targeted Lipid Nanoparticles for Retinal Drug Delivery

Item type:	Thesis of the University of Regensburg (PhD)
Date:	4 October 2022
Referee:	Prof. Dr. Achim Göpferich and Prof. Dr. Ernst Tamm
Date of exam:	14 October 2021
Institutions:	Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich)
Keywords:	Lipid nanoparticles, nanotherapeutic, bio-mimetic, retinal disease, drug delivery
Dewey Decimal Classification:	500 Science > 500 Natural sciences & mathematics 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy
Status:	Published
Refereed:	Yes, this version has been refereed
Created at the University of Regensburg:	Yes
Item ID:	50844

Abstract (English)

This work has elucidated the potential of bio-inspired lipid nanoparticles for targeted retinal drug delivery. The functionalization of lipid nanocapsules (LNCs) with an αvβ3 integrinspecific ligand endowed the particles with the ability to not only target retinal endothelial cells but evade from the systemic circulation and accumulate in retinal pigment epithelial (RPE) cells upon systemic ...

Abstract (English)

This work has elucidated the potential of bio-inspired lipid nanoparticles for targeted retinal drug delivery. The functionalization of lipid nanocapsules (LNCs) with an αvβ3 integrinspecific ligand endowed the particles with the ability to not only target retinal endothelial cells but evade from the systemic circulation and accumulate in retinal pigment epithelial (RPE) cells upon systemic administration. By loading these particles with CsA, therapeutic effects on neovascularization and inflammation were achieved in vivo, even though in vitro efficacy was lacking. Taken all together, the described findings demonstrate the distinct potential of bio-inspired lipid nanoparticles for retinal drug delivery, as the use of targeted nanoparticles was required to obtain therapeutic effects. It is believed that these findings have the potential to pave the way for the development of a single dose intravenous treatment for ROP. Even though, further research and development is needed to successfully translate the nanotherapeutic into clinics, the nanotherapeutic approach could represent a paradigm shift in neonatal care to a future in which a single intravenous injection of drug loaded nanoparticles is a standard treatment for millions of infants at risk for ROP and further points towards a future of comprehensive and causal therapies for a plethora of degenerative retinal diseases.

Translation of the abstract (German)

Diese Arbeit beschreibt die Entwicklung von Cyclosporin A beladene Lipid Nanokapseln, die in der Lage sind, Arzneistoffe in Zellen des retinalen Pigmentepithels (RPE), einer Zellschicht mit hoher Relevanz für Erkrankungen der Retina, zu transportieren. Durch ihren Aufbau aus Lipiden und mit Hilfe eines Liganden an der Oberfläche sind die Nanopartikel in der Lage sich in den Zellen anzureichern, ...

Translation of the abstract (German)

Diese Arbeit beschreibt die Entwicklung von Cyclosporin A beladene Lipid Nanokapseln, die in der Lage sind, Arzneistoffe in Zellen des retinalen Pigmentepithels (RPE), einer Zellschicht mit hoher Relevanz für Erkrankungen der Retina, zu transportieren. Durch ihren Aufbau aus Lipiden und mit Hilfe eines Liganden an der Oberfläche sind die Nanopartikel in der Lage sich in den Zellen anzureichern, die bisher vollkommen unzugänglich waren. Nach Beladung mit Cyclosporin A zeigten die Partikel bei i.v. Applikation im einschlägigen Krankheitsmodell der Maus sehr hohe Wirksamkeit für die Behandlung multifaktorieller, retinaler Augenerkrankungen wie altersbedingter Makuladegeneration, diabetischer Retinopathie und Frühgeborenen-Retinopathie.

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Abstract (English)

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Translation of the abstract (German)

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