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author:

Gao, Yu (Gao, Yu.) [1] (Scholars:高瑜) | Kraft, John C. (Kraft, John C..) [2] | Yu, Danni (Yu, Danni.) [3] | Ho, Rodney J. Y. (Ho, Rodney J. Y..) [4]

Indexed by:

Scopus SCIE

Abstract:

Combination antiretroviral therapy (cART) given orally has transformed HIV from a terminal illness to a manageable chronic disease. Yet despite the recent development of newer and more potent drugs for cART and suppression of virus in blood to undetectable levels, residual virus remains in tissues. Upon stopping cART, virus rebounds and progresses to AIDS. Current oral cART regimens have several drawbacks including (1) challenges in patient adherence due to pill fatigue or side-effects, (2) the requirement of life-long daily drug intake, and (3) limited penetration and retention in cells within lymph nodes. Appropriately designed injectable nano-drug combinations that are long-acting and retained in HIV susceptible cells within lymph nodes may address these challenges. While a number of nanomaterials have been investigated for delivery of HIV drugs and drug combinations, key challenges involve developing and scaling delivery systems that provide a drug combination targeted to HIV host cells and tissues where residual virus persists. With validation of the drug-insufficiency hypothesis in lymph nodes, progress has been made in the development of drug combination nanoparticles that are long-acting and targeted to lymph nodes and cells. Unique drug combination nanoparticles (DcNPs) composed of three HIV drugs-lopinavir, ritonavir, and tenofovir-have been shown to provide enhanced drug levels in lymph nodes; and elevated drug-combination levels in HIV-host cells in the blood and plasma for two weeks. This review summarizes the progress in the development of nanoparticle-based drug delivery systems for HIV therapy. It discusses how injectable nanocarriers may be designed to enable delivery of drug combinations that are long-lasting and target-selective in physiological contexts (in vivo) to provide safe and effective use. Consistent drug combination exposure in the sites of residual HIV in tissues and cells may overcome drug insufficiency observed in patients on oral cART.

Keyword:

Drug combination HIV/AIDS Long-acting Nanomedicine Targeted

Community:

  • [ 1 ] [Gao, Yu]Fuzhou Univ, Coll Chem, Canc Metastasis Alert & Prevent Ctr, Fuzhou 350108, Fujian, Peoples R China
  • [ 2 ] [Gao, Yu]Fuzhou Univ, Coll Chem, Fujian Prov Key Lab Canc Metastasis Chemoprevent, Fuzhou 350108, Fujian, Peoples R China
  • [ 3 ] [Gao, Yu]Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA
  • [ 4 ] [Kraft, John C.]Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA
  • [ 5 ] [Yu, Danni]Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA
  • [ 6 ] [Ho, Rodney J. Y.]Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA
  • [ 7 ] [Ho, Rodney J. Y.]Univ Washington, Dept Bioengn, Seattle, WA 98195 USA

Reprint 's Address:

  • [Ho, Rodney J. Y.]Univ Washington, Box 357610, Seattle, WA 98195 USA

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Source :

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

ISSN: 0939-6411

Year: 2019

Volume: 138

Page: 75-91

4 . 6 0 4

JCR@2019

4 . 4 0 0

JCR@2023

ESI Discipline: PHARMACOLOGY & TOXICOLOGY;

ESI HC Threshold:136

CAS Journal Grade:2

Cited Count:

WoS CC Cited Count: 35

SCOPUS Cited Count: 39

ESI Highly Cited Papers on the List: 1 Unfold All

  • 2020-1

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 1

Online/Total:140/10019117
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