Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects.

AIDS Research and Therapy
Li WanPatrick J Sinko

Abstract

Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties. Bioconjugates were prepared from different combinations of the approved drug, saquinavir, the antiviral agent, R.I.CK-Tat9, the polymeric carrier, poly(ethylene) glycol and the cell uptake enhancer, biotin. Anti-HIV activities were measured in MT-2 cells, an HTLV-1-transformed human lymphoid cell line, infected with HIV-1 strain Vbu 3, while parallel studies were performed in uninfected cells to determine cellular toxicity. For example, R.I.CK-Tat9 was 60 times more poten...Continue Reading

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Citations

Aug 26, 2010·Nanomedicine·Joaquin SanchisMaría J Vicent
Oct 29, 2013·Annual Review of Pharmacology and Toxicology·Matthew PalomboPatrick J Sinko
Aug 3, 2007·Journal of Drug Targeting·Hui DingJindrich Kopecek
Nov 28, 2009·Advanced Drug Delivery Reviews·Simi GunaseelanPatrick J Sinko
May 17, 2012·Viruses·Raveen ParboosingHendrik G Kruger
Jun 22, 2017·Therapeutic Delivery·Blessing A Aderibigbe
Jun 27, 2009·Expert Opinion on Therapeutic Patents·John Howl, Sarah Jones

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Methods Mentioned

BETA
pharmacotherapy
flow
confocal microscopy
size-exclusion chromatography
protease assay
fluorescence microscopy
flow cytometry
confocal

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