Universität zu Köln

Martens, Thomas F., Peynshaert, Karen ORCID: 0000-0002-2987-4938, Nascimento, Thais Leite ORCID: 0000-0002-2656-7609, Fattal, Elias ORCID: 0000-0002-3194-961X, Karlstetter, Marcus, Langmann, Thomas, Picaud, Serge ORCID: 0000-0002-0548-5145, Demeester, Jo, De Smedt, Stefaan C., Remaut, Katrien ORCID: 0000-0002-2244-1339 and Braeckmans, Kevin (2017). Effect of hyaluronic acid-binding to lipoplexes on intravitreal drug delivery for retinal gene therapy. Eur. J. Pharm. Sci., 103. S. 27 - 36. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1879-0720

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Abstract

Intravitreal administration of nanomedicines could be valuable for retinal gene therapy, if their mobility in the vitreous and therapeutic efficacy in the target cells can be guaranteed. Hyaluronic acid (HA) as an electrostatic coating of polymeric gene nanomedicines has proven to be beneficial on both accounts. While electrostatic coating provides an easy way of coating cationic nanoparticles, the stability of electrostatic complexes in vivo is uncertain. In this study, therefore, we compare electrostatic with covalent coating of gene nanocarriers with HA for retinal gene therapy via intravitreal administration. Specifically, DOTAP:DOPE/plasmid DNA lipoplexes coated with HA are evaluated in terms of intravitreal mobility using a previously optimized ex vivo model. We find that both electrostatic and covalent HA coating considerably improve the mobility of the lipoplexes in the vitreous humor of excised bovine eyes. In addition we evaluate in vitro uptake and transfection efficiency in ARPE-19 cells. Contrary to PEGylated lipoplexes it is found that HA coated lipoplexes are efficiently internalized into ARPE-19 cells. Covalent HA-coated lipoplexes had an 8-fold increase of transgene expression compared to the un-coated lipoplexes. We conclude that covalent HA-coating of gene nanomedicines is a promising approach for retinal gene therapy by intravitreal administration. (C) 2017 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Martens, Thomas F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peynshaert, Karen UNSPECIFIED orcid.org/0000-0002-2987-4938 UNSPECIFIED Nascimento, Thais Leite UNSPECIFIED orcid.org/0000-0002-2656-7609 UNSPECIFIED Fattal, Elias UNSPECIFIED orcid.org/0000-0002-3194-961X UNSPECIFIED Karlstetter, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Picaud, Serge UNSPECIFIED orcid.org/0000-0002-0548-5145 UNSPECIFIED Demeester, Jo UNSPECIFIED UNSPECIFIED UNSPECIFIED De Smedt, Stefaan C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Remaut, Katrien UNSPECIFIED orcid.org/0000-0002-2244-1339 UNSPECIFIED Braeckmans, Kevin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-230652
DOI:	10.1016/j.ejps.2017.02.027
Journal or Publication Title:	Eur. J. Pharm. Sci.
Volume:	103
Page Range:	S. 27 - 36
Date:	2017
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1879-0720
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SOLID LIPID NANOPARTICLES; PIGMENT EPITHELIUM; EXTRACELLULAR GLYCOSAMINOGLYCANS; INTRACELLULAR TRAFFICKING; MOLECULAR-WEIGHT; NANOMEDICINES; LIPOSOMES; MOVEMENT; BARRIERS; VECTORS Multiple languages Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23065