Ετικέτες

Δευτέρα 8 Μαΐου 2017

Effect of hyaluronic acid-binding to lipoplexes on intravitreal drug delivery for retinal gene therapy

Publication date: 30 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 103
Author(s): Thomas F Martens, Karen Peynshaert, Thaís Leite Nascimento, Elias Fattal, Marcus Karlstetter, Thomas Langmann, Serge Picaud, Jo Demeester, Stefaan C De Smedt, Katrien Remaut, Kevin Braeckmans
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 uncoated lipoplexes. We conclude that covalent HA-coating of gene nanomedicines is a promising approach for retinal gene therapy by intravitreal administration.

Graphical abstract

image


http://ift.tt/2qUFdAJ

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου

Αναζήτηση αυτού του ιστολογίου