Site-specific administration of antisense oligonucleotides using biodegradable polymer microspheres provides sustained delivery and improved subcellular biodistribution in the neostriatum of the rat brain

Journal of Drug Targeting
A KhanS Akhtar

Abstract

Antisense oligonucleotides (ODNs) are being increasingly used in the central nervous system as biological tools, as drug-target validation agents and as potential therapeutic agents. Although the local delivery of naked ODNs to the brain can result in the desired biological effects, the duration of efficacy is relatively short lived due to the combined effects of rapid ODN degradation and elimination half-lives in vivo. In this study, we have examined the use of biodegradable polymer microspheres as a site-specific delivery system for targeting ODNs to the neostriatum of the rat brain. Model phosphorothioate backbone-modified ODNs were entrapped within poly(D,L-lactide-co-glycolide) (PLAGA) microspheres using a double emulsion-deposition method and the formulations characterised in terms of particle size, surface morphology, percent encapsulation efficiency, ODN loading and in vitro release profiles. For in vivo evaluation, PLAGA microspheres containing fluorescently-labelled ODNs were stereo-taxically administered to the neostriatum of the rat brain and biodistribution of ODNs monitored after 48 h. Administration of free fluorescently-labelled ODNs to the neostriatum resulted in a punctate cellular distribution of ODNs after 2...Continue Reading

References

Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·S AgrawalJ Y Tang
Jul 1, 1971·Oral Surgery, Oral Medicine, and Oral Pathology·D E CutrightB Perez
Oct 1, 1994·Cellular and Molecular Neurobiology·B J ChiassonH A Robertson
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·W M PardridgeY S Kang
Feb 1, 1994·Trends in Pharmacological Sciences·C Wahlestedt
Jan 1, 1995·Critical Reviews in Therapeutic Drug Carrier Systems·H Okada, H Toguchi
Jan 1, 1997·Trends in Pharmacological Sciences·S Akhtar, S Agrawal
Sep 1, 1997·Neurochemistry International·A Szklarczyk, L Kaczmarek
Jul 24, 1998·Brain Research. Molecular Brain Research·B J ChiassonH A Robertson
Aug 26, 1998·European Journal of Pharmacology·H Zhu, I K Ho

❮ Previous
Next ❯

Citations

Sep 2, 2008·Pharmaceutical Research·Ripal GaudanaAshim K Mitra
Oct 18, 2000·Advanced Drug Delivery Reviews·S AkhtarP Sayyed
Mar 21, 2001·Drug Discovery Today·M D. HughesS Akhtar
Jun 26, 2009·Expert Opinion on Drug Delivery·Xiubo ZhaoJian R Lu
Nov 17, 2004·Journal of Drug Targeting·Ian R GilmoreSaghir Akhtar
Sep 1, 2004·International Journal of Pharmaceutics·S Freiberg, X X Zhu
Oct 12, 2004·Experimental Neurology·Kevin J Whittlesey, Lonnie D Shea
Nov 14, 2006·Advanced Drug Delivery Reviews·Elias Fattal, Amélie Bochot
Jan 24, 2003·Expert Opinion on Therapeutic Targets·Terace M Fletcher
Jun 5, 2003·Expert Opinion on Therapeutic Targets·Jenny Godfray, Peter Estibeiro

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.