Novel elvitegravir nanoformulation approach to suppress the viral load in HIV-infected macrophages

Yuqing Gong, Pallabita Chowdhury, Narasimha M. Midde, Mohammad A. Rahman, Murali Yallapu, Santosh Kumar

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose Monocytes serve as sanctuary sites for HIV-1 from which virus is difficult to be eliminated. Therefore, an effective viral suppression in monocytes is critical for effective antiretroviral therapy (ART). This study focuses on a new strategy using nanoformulation to optimize the efficacy of ART drugs in HIV-infected monocytes. Methods Poly(lactic-co-glycolic acid) (PLGA)-based elvitegravir nanoparticles (PLGA-EVG) were prepared by nano-precipitation technique. The physicochemical properties of PLGA-EVG were characterized using transmission electron microscopy, dynamic light scattering, and Fourier-transform infrared spectroscopy. Cellular uptake study was performed by fluorescence microscopy and flow cytometry. All in vitro experiments were performed by using HIV-infected monocytic cell lines U1 and HIV-infected primary macrophages. Elvitegravir quantification was performed using LC-MS/MS. HIV viral replication was assessed by using p24 ELISA. Results We developed a PLGA-EVG nanoparticle formulation with particle size of ~ 47 nm from transmission electron microscopy and zeta potential of ~ 6.74 mV from dynamic light scattering. These nanoparticles demonstrated a time- and concentration-dependent uptakes in monocytes. PLGA-EVG formulation showed a ~ 2 times higher intracellular internalization of EVG than control group (EVG alone). PLGA-EVG nanoparticles also demonstrated superior viral suppression over control for a prolonged period of time. Conclusions PLGA-based EVG nanoformulation increased the intracellular uptake of EVG, as well as enhanced viral suppression in HIV-infected macrophages, suggesting its potential for improved HIV treatment in monocytic cells.

Original languageEnglish (US)
Pages (from-to)214-219
Number of pages6
JournalBiochemistry and Biophysics Reports
Volume12
DOIs
StatePublished - Dec 1 2017

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Macrophages
Viral Load
HIV
Nanoparticles
Monocytes
Dynamic light scattering
Transmission Electron Microscopy
Transmission electron microscopy
Drug therapy
Flow cytometry
Fluorescence microscopy
Fourier Transform Infrared Spectroscopy
Zeta potential
Viruses
Fluorescence Microscopy
Particle Size
JTK 303
polylactic acid-polyglycolic acid copolymer
HIV-1
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Novel elvitegravir nanoformulation approach to suppress the viral load in HIV-infected macrophages. / Gong, Yuqing; Chowdhury, Pallabita; Midde, Narasimha M.; Rahman, Mohammad A.; Yallapu, Murali; Kumar, Santosh.

In: Biochemistry and Biophysics Reports, Vol. 12, 01.12.2017, p. 214-219.

Research output: Contribution to journalArticle

Gong, Yuqing ; Chowdhury, Pallabita ; Midde, Narasimha M. ; Rahman, Mohammad A. ; Yallapu, Murali ; Kumar, Santosh. / Novel elvitegravir nanoformulation approach to suppress the viral load in HIV-infected macrophages. In: Biochemistry and Biophysics Reports. 2017 ; Vol. 12. pp. 214-219.
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