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Pharmacokinetics of pullulan–dexamethasone conjugates in retinal drug delivery

Authors :
Eva Kicková
Amir Sadeghi
Jooseppi Puranen
Shirin Tavakoli
Merve Sen
Veli-Pekka Ranta
Blanca Arango-Gonzalez
Sylvia Bolz
Marius Ueffing
Stefano Salmaso
Paolo Caliceti
Elisa Toropainen
Marika Ruponen
Arto Urtti
Source :
Pharmaceutics, Pharmaceutics, Vol 14, Iss 12, p 12 (2022)
Publication Year :
2022
Publisher :
MDPI, 2022.

Abstract

The treatment of retinal diseases by intravitreal injections requires frequent administration unless drug delivery systems with long retention and controlled release are used. In this work, we focused on pullulan (≈67 kDa) conjugates of dexamethasone as therapeutic systems for intravitreal administration. The pullulan–dexamethasone conjugates self-assemble into negatively charged nanoparticles (average size 326 ± 29 nm). Intravitreal injections of pullulan and pullulan–dexamethasone were safe in mouse, rat and rabbit eyes. Fluorescently labeled pullulan particles showed prolonged retention in the vitreous and they were almost completely eliminated via aqueous humor outflow. Pullulan conjugates also distributed to the retina via Müller glial cells when tested in ex vivo retina explants and in vivo. Pharmacokinetic simulations showed that pullulan–dexamethasone conjugates may release free and active dexamethasone in the vitreous humor for over 16 days, even though a large fraction of dexamethasone may be eliminated from the eye as bound pullulan–dexamethasone. We conclude that pullulan based drug conjugates are promising intravitreal drug delivery systems as they may reduce injection frequency and deliver drugs into the retinal cells.

Details

Language :
English
Database :
OpenAIRE
Journal :
Pharmaceutics, Pharmaceutics, Vol 14, Iss 12, p 12 (2022)
Accession number :
edsair.pmid.dedup....628ca80882123ab711eaac5584dfd64b