Intravitreal Polymeric Nanocarriers with Long Ocular Retention and Targeted Delivery to the Retina and Optic Nerve Head Region

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Junnuthula , V , Sadeghi Boroujeni , A , Cao , S , Tavakoli , S , Ridolfo , R , Toropainen , E , Ruponen , M , van Hest , J C M & Urtti , A 2021 , ' Intravitreal Polymeric Nanocarriers with Long Ocular Retention and Targeted Delivery to the Retina and Optic Nerve Head Region ' , Pharmaceutics , vol. 13 , no. 4 , 445 . https://doi.org/10.3390/pharmaceutics13040445

Title: Intravitreal Polymeric Nanocarriers with Long Ocular Retention and Targeted Delivery to the Retina and Optic Nerve Head Region
Author: Junnuthula, Vijayabhaskarreddy; Sadeghi Boroujeni, Amir; Cao, Shoupeng; Tavakoli, Shirin; Ridolfo, Roxane; Toropainen, Elisa; Ruponen, Marika; van Hest, Jan C. M.; Urtti, Arto
Contributor organization: Divisions of Faculty of Pharmacy
Drug Delivery Unit
Drug Research Program
Pharmaceutical Nanotechnology
Division of Pharmaceutical Biosciences
Drug Delivery
Date: 2021-04
Language: eng
Number of pages: 13
Belongs to series: Pharmaceutics
ISSN: 1999-4923
DOI: https://doi.org/10.3390/pharmaceutics13040445
URI: http://hdl.handle.net/10138/330139
Abstract: Posterior eye tissues, such as retina, are affected in many serious eye diseases, but drug delivery to these targets is challenging due to various anatomical eye barriers. Intravitreal injections are widely used, but the intervals between invasive injections should be prolonged. We synthesized and characterized (H-1 NMR, gel permeation chromatography) block copolymers of poly(ethylene glycol), poly(caprolactone), and trimethylene carbonate. These polymers self-assembled to polymersomes and polymeric micelles. The mean diameters of polymersomes and polymeric micelles, about 100 nm and 30-50 nm, respectively, were obtained with dynamic light scattering. Based on single particle tracking and asymmetric flow field-flow fractionation, the polymeric micelles and polymersomes were stable and diffusible in the vitreous. The materials did not show cellular toxicity in cultured human umbilical vein endothelial cells in the Alamar Blue Assay. Pharmacokinetics of the intravitreal nanocarriers in the rabbits were evaluated using in vivo fluorophotometry. The half-lives of the polymersomes (100 nm) and the micelles (30 nm) were 11.4-32.7 days and 4.3-9.5 days. The intravitreal clearance values were 1.7-8.7 mu L/h and 3.6-5.4 mu L/h for polymersomes and polymeric micelles, respectively. Apparent volumes of distribution of the particles in the rabbit vitreous were 0.6-1.3 mL for polymeric micelles and 1.9-3.4 mL for polymersomes. Polymersomes were found in the vitreous for at least 92 days post-dosing. Furthermore, fundus imaging revealed that the polymersomes accumulated near the optic nerve and retained there even at 111 days post-injection. Polymersomes represent a promising technology for controlled and site-specific drug delivery in the posterior eye segment.
Subject: intravitreal
polymersome
polymeric micelle
drug delivery
retina
optic nerve
DRUG-DELIVERY
PHARMACOKINETICS
POSTERIOR
MICELLES
SIZE
EYE
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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