Pharmacokinetics of Pullulan-Dexamethasone Conjugates in Retinal Drug Delivery

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Kickova , E , Sadeghi , A , Puranen , J , Tavakoli , S , Sen , M , Ranta , V-P , Arango-Gonzalez , B , Bolz , S , Ueffing , M , Salmaso , S , Caliceti , P , Toropainen , E , Ruponen , M & Urtti , A 2022 , ' Pharmacokinetics of Pullulan-Dexamethasone Conjugates in Retinal Drug Delivery ' , Pharmaceutics , vol. 14 , no. 1 , 12 . https://doi.org/10.3390/pharmaceutics14010012

Title: Pharmacokinetics of Pullulan-Dexamethasone Conjugates in Retinal Drug Delivery
Author: Kickova, Eva; Sadeghi, Amir; Puranen, Jooseppi; Tavakoli, Shirin; Sen, Merve; Ranta, Veli-Pekka; Arango-Gonzalez, Blanca; Bolz, Sylvia; Ueffing, Marius; Salmaso, Stefano; Caliceti, Paolo; Toropainen, Elisa; Ruponen, Marika; Urtti, Arto
Contributor organization: Pharmaceutical Nanotechnology
Drug Delivery Unit
Division of Pharmaceutical Biosciences
Drug Research Program
Drug Delivery
Date: 2022-01
Language: eng
Number of pages: 24
Belongs to series: Pharmaceutics
ISSN: 1999-4923
DOI: https://doi.org/10.3390/pharmaceutics14010012
URI: http://hdl.handle.net/10138/340594
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 (approximate to 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 Muller 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.
Subject: pullulan
dexamethasone
conjugate
retinal drug delivery
ocular fluorophotometry
optical coherence tomography
pharmacokinetics
INTRAVITREAL INJECTION
CONTROLLED-RELEASE
MULLER CELLS
IN-VITRO
IMPLANT
RABBIT
SYSTEM
GENE
PHOTORECEPTORS
NANOPARTICLES
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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