Document Detail


Functional proteome of macrophage carried nanoformulated antiretroviral therapy demonstrates enhanced particle carrying capacity.
MedLine Citation:
PMID:  23544708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our laboratory developed long-acting nanoformulations of antiretroviral therapy (nanoART) to improve drug compliance, reduce toxicities, and facilitate access of drug to viral reservoirs. These all function to inevitably improve treatment of human immunodeficiency virus (HIV) infection. Formulations are designed to harness the carrying capacities of mononuclear phagocytes (MP; monocytes and macrophages) and to use these cells as Trojan horses for drug delivery. Such a drug distribution system limits ART metabolism and excretion while facilitating access to viral reservoirs. Our prior works demonstrated a high degree of nanoART sequestration in macrophage recycling endosomes with broad and sustained drug tissue biodistribution and depots with limited untoward systemic toxicities. Despite such benefits, the effects of particle carriage on the cells' functional capacities remained poorly understood. Thus, we employed pulsed stable isotope labeling of amino acids in cell culture to elucidate the macrophage proteome and assess any alterations in cellular functions that would affect cell-drug carriage and release kinetics. NanoART-MP interactions resulted in the induction of a broad range of activation-related proteins that can enhance phagocytosis, secretory functions, and cell migration. Notably, we now demonstrate that particle-cell interactions serve to enhance drug loading while facilitating drug tissue depots and transportation.
Authors:
Andrea L Martinez-Skinner; Ram S Veerubhotla; Han Liu; Huangui Xiong; Fang Yu; JoEllyn M McMillan; Howard E Gendelman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-04-17
Journal Detail:
Title:  Journal of proteome research     Volume:  12     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-03     Completed Date:  2013-12-03     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2282-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / chemistry,  pharmacology*
Benzoxazines / chemistry,  pharmacology
Cell Movement
Cells, Cultured
Chemokines / metabolism,  secretion
Cytoskeletal Proteins / metabolism
Drug Carriers / chemistry,  pharmacology*
Drug Compounding
Humans
Macrophages / drug effects,  metabolism*,  secretion
Membrane Potentials / drug effects
Nanoparticles / chemistry
Oligopeptides / chemistry,  pharmacology
Particle Size
Phagocytosis / drug effects
Potassium Channels / metabolism
Proteome / metabolism*
Pyridines / chemistry,  pharmacology
Ritonavir / chemistry,  pharmacology
Grant Support
ID/Acronym/Agency:
2R01 NS034239/NS/NINDS NIH HHS; P01 DA026146/DA/NIDA NIH HHS; P01 DA028555/DA/NIDA NIH HHS; P01 DA028555/DA/NIDA NIH HHS; P01 MH064570/MH/NIMH NIH HHS; P01 MH64570/MH/NIMH NIH HHS; P01 NS031492/NS/NINDS NIH HHS; P01 NS043985/NS/NINDS NIH HHS; P01 NS31492/NS/NINDS NIH HHS; P01 NS43985/NS/NINDS NIH HHS; P30 GM103509/GM/NIGMS NIH HHS; P30 MH062261/MH/NIMH NIH HHS; P30MH062261/MH/NIMH NIH HHS; R01 NS034239/NS/NINDS NIH HHS; R01 NS036126/NS/NINDS NIH HHS; R01 NS036127/NS/NINDS NIH HHS; R01 NS077873/NS/NINDS NIH HHS; R01 NS36126/NS/NINDS NIH HHS; R01NS077873/NS/NINDS NIH HHS; R13 NS083315/NS/NINDS NIH HHS; R37 NS036126/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Benzoxazines; 0/Chemokines; 0/Cytoskeletal Proteins; 0/Drug Carriers; 0/Oligopeptides; 0/Potassium Channels; 0/Proteome; 0/Pyridines; JE6H2O27P8/efavirenz; O3J8G9O825/Ritonavir; QZU4H47A3S/atazanavir
Comments/Corrections

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