Sustained release of nanosized complexes of polyethylenimine and anti-TGF-beta 2 oligonucleotide improves the outcome of glaucoma surgery.

Details

Serval ID
serval:BIB_61D76C5069C6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sustained release of nanosized complexes of polyethylenimine and anti-TGF-beta 2 oligonucleotide improves the outcome of glaucoma surgery.
Journal
Journal of Controlled Release : Official Journal of the Controlled Release Society
Author(s)
Gomes dos Santos A.L., Bochot A., Doyle A., Tsapis N., Siepmann J., Siepmann F., Schmaler J., Besnard M., Behar-Cohen F., Fattal E.
ISSN
0168-3659 (Print)
ISSN-L
0168-3659
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
112
Number
3
Pages
369-381
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
The purpose of this study was to design microspheres combining sustained delivery and enhanced intracellular penetration for ocular administration of antisense oligonucleotides. Nanosized complexes of antisense TGF-beta2 phosphorothioate oligonucleotides (PS-ODN) with polyethylenimine (PEI), and naked PS-ODN were encapsulated into poly(lactide-co-glycolide) microspheres prepared by the double-emulsion solvent evaporation method. The PS-ODN was introduced either naked or complexed in the inner aqueous phase of the first emulsion. We observed a marked influence of microsphere composition on porosity, size distribution and PS-ODN encapsulation efficiency. Mainly, the presence of PEI induced the formation of large pores observed onto microsphere surface. Introduction of NaCl in the outer aqueous phase increased the encapsulation efficiency and reduced microsphere porosity. In vitro release kinetic of PS-ODN was also investigated. Clearly, the higher the porosity, the faster was the release and the higher was the burst effect. Using an analytical solution of Fick's second law of diffusion, it was shown that the early phase of PS-ODN and PS-ODN-PEI complex release was primarily controlled by pure diffusion, irrespectively of the type of microsphere. Finally, microspheres containing antisense TGF-beta2 nanosized complexes were shown, after subconjunctival administration to rabbit, to significantly increase intracellular penetration of ODN in conjunctival cells and subsequently to improve bleb survival in a rabbit experimental model of filtering surgery. These results open up interesting prospective for the local controlled delivery of genetic material into the eye.
Keywords
Animals, Conjunctiva/drug effects, Delayed-Action Preparations/administration & dosage, Female, Glaucoma/drug therapy, Glaucoma/surgery, Nanostructures, Oligonucleotides, Antisense/administration & dosage, Oligonucleotides, Antisense/pharmacokinetics, Polyethyleneimine/administration & dosage, Rabbits, Thionucleotides/administration & dosage, Thionucleotides/pharmacokinetics, Transforming Growth Factor beta/administration & dosage, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta2
Pubmed
Create date
26/09/2013 15:34
Last modification date
20/08/2019 14:18
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