Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment

Antoinette G. Nelson, Xiaoping Zhang, Usha Ganapathi, Zoltan Szekely, Charles Williams Flexner, Andrew Owen, Patrick J. Sinko

Research output: Contribution to journalArticle

Abstract

The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection.

Original languageEnglish (US)
Pages (from-to)669-680
Number of pages12
JournalJournal of Controlled Release
Volume219
DOIs
StatePublished - Dec 10 2015

Fingerprint

Drug Delivery Systems
Acquired Immunodeficiency Syndrome
HIV
HIV Infections
Pharmaceutical Preparations
Therapeutics
Therapeutic Human Experimentation
Anti-HIV Agents
Highly Active Antiretroviral Therapy
Anniversaries and Special Events
Patient Compliance
Pre-Exposure Prophylaxis
Mucous Membrane
Lymph Nodes
Technology
Infection
Research

Keywords

  • Antiretroviral drugs (ARV)
  • Drug delivery targeting
  • HIV/AIDS
  • Long-acting/extended-release (LA/ER)
  • Nanomedicine
  • Nanotechnology
  • Pre-exposure prophylaxis (PrEP)

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment. / Nelson, Antoinette G.; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles Williams; Owen, Andrew; Sinko, Patrick J.

In: Journal of Controlled Release, Vol. 219, 10.12.2015, p. 669-680.

Research output: Contribution to journalArticle

Nelson, Antoinette G. ; Zhang, Xiaoping ; Ganapathi, Usha ; Szekely, Zoltan ; Flexner, Charles Williams ; Owen, Andrew ; Sinko, Patrick J. / Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment. In: Journal of Controlled Release. 2015 ; Vol. 219. pp. 669-680.
@article{9cd074526fd94078a50efe7be96fcf5d,
title = "Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment",
abstract = "The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection.",
keywords = "Antiretroviral drugs (ARV), Drug delivery targeting, HIV/AIDS, Long-acting/extended-release (LA/ER), Nanomedicine, Nanotechnology, Pre-exposure prophylaxis (PrEP)",
author = "Nelson, {Antoinette G.} and Xiaoping Zhang and Usha Ganapathi and Zoltan Szekely and Flexner, {Charles Williams} and Andrew Owen and Sinko, {Patrick J.}",
year = "2015",
month = "12",
day = "10",
doi = "10.1016/j.jconrel.2015.08.042",
language = "English (US)",
volume = "219",
pages = "669--680",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

TY - JOUR

T1 - Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment

AU - Nelson, Antoinette G.

AU - Zhang, Xiaoping

AU - Ganapathi, Usha

AU - Szekely, Zoltan

AU - Flexner, Charles Williams

AU - Owen, Andrew

AU - Sinko, Patrick J.

PY - 2015/12/10

Y1 - 2015/12/10

N2 - The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection.

AB - The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection.

KW - Antiretroviral drugs (ARV)

KW - Drug delivery targeting

KW - HIV/AIDS

KW - Long-acting/extended-release (LA/ER)

KW - Nanomedicine

KW - Nanotechnology

KW - Pre-exposure prophylaxis (PrEP)

UR - http://www.scopus.com/inward/record.url?scp=84947491299&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947491299&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2015.08.042

DO - 10.1016/j.jconrel.2015.08.042

M3 - Article

C2 - 26315816

AN - SCOPUS:84947491299

VL - 219

SP - 669

EP - 680

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -