Home
Resource
Macrophage targeting using nanotechnology for HIV therapy
PDF
PDF format is widely accepted and good for printing.
Plug-in required
PDF-1(15.58 MB)
Citation & Export
View Usage Statistics
Staff View

Citation & Export
Hide

Simple citation

Chen, Pei-Ming. Macrophage targeting using nanotechnology for HIV therapy. Retrieved from https://doi.org/doi:10.7282/T3P55M8Z

Export

Click here for information about Citation Management Tools at Rutgers.

Statistics
Hide

Description

TitleMacrophage targeting using nanotechnology for HIV therapy
NameChen, Pei-Ming (author); Sinko, Patrick John (chair); Suh, Nanjoo (internal member); You, Guofeng (internal member); Prud'homme, Robert Kraft (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2012
Other Date2012-10 (degree)
SubjectPharmaceutical Science, Macrophages, Drug delivery systems, HIV infections--Treatment
Extentx, 120 p. : ill.
DescriptionMacrophages (MΦ) are involved in a number of pathological conditions, such as HIV infection/AIDS, tuberculosis, tumor development and atherosclerosis. The macrophage mannose receptor (MR) is expressed on the cell surface of tissue MΦ where it mediates the internalization of glycoproteins and glycoconjugates via both the endocytic and phagocytic pathways. The theme of the current study is to develop a nano-sized therapeutic delivery system that targets the MΦ MR. A series of mannosylated NCs were designed and synthesized to systematically evaluate the effects of mannose copy number, mannose ligand spacing and poly (ethylene glycol) (PEG) size on NC uptake via MR. Targeted nanocarriers (NCs) bearing mannose moieties were evaluated for targeting in MΦ cell lines. The first study demonstrated three important structural requirements for optimal mannose-targeted NC cellular uptake - two copies of the targeting ligand mannose were required, a 46.5 Å PEG spacer in between ligands was optimal and 12 kDa PEG size. Furthermore, the effect of MΦ polarization on NC uptake was also investigated. Rat peritoneal MΦs were polarized into classically activated (M1) and alternatively activated (M2a) phenotypes. The Western blot results showed the highest expression of MR on the M2a phenotype. Using confocal microscopy and a fluorescence microscope, 12-fold higher uptake of NC (2 copy mannose) was observed in M2aMΦ as compared to M1MΦ, suggesting great potential in selective MΦ cellular targeting. Drug-loaded NCs were prepared using a nucleoside reverse transcriptase inhibitor (AZT) or a protease inhibitor (RTV) conjugated to a NC with 2 copies of mannose linked by a PEG12 (46.5 Å) spacer. Anti-HIV activities of the drug conjugated NCs were assessed using U937/HIV-2MS cells and HIV-1 infected human monocyte derived MΦs and were based on a reduction in viral matrix protein p24 production. The results showed significant p24 reduction with EC50’s ranging from 5.7 uM to 25 uM indicating significant anti-HIV activity. Taken together, the studies presented in this dissertation identified the optimum configuration of drug loaded NCs for targeting the MΦ MR. Furthermore, the positive anti-HIV activities suggest that the NC approach holds great promise for receptor targeted drug delivery to HIV-infected MΦs.
NotePh.D.
NoteIncludes bibliographical references
NoteIncludes vita
Noteby Pei-Ming Chen
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T3P55M8Z
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Version 8.5.5
Rutgers University Libraries - Copyright ©2024