N-Butyldeoxynojirimycin is a broadly effective anti-HIV therapy significantly enhanced by targeted liposome delivery.

Pollock, S; Dwek, R; Burton, D; Zitzmann, N

Journal article

N-Butyldeoxynojirimycin is a broadly effective anti-HIV therapy significantly enhanced by targeted liposome delivery.

Abstract:: OBJECTIVE: N-Butyldeoxynojirimycin (NB-DNJ), an inhibitor of HIV gp120 folding, was assessed as a broadly active therapy for the treatment of HIV/AIDS. Furthermore, to reduce the effective dose necessary for antiviral activity, NB-DNJ was encapsulated inside liposomes and targeted to HIV-infected cells. METHODS: Thirty-one primary isolates of HIV (including drug-resistant isolates) were cultured in peripheral blood mononuclear cells to quantify the effect of NB-DNJ on viral infectivity. pH-sensitive liposomes capable of mediating the intracellular delivery of NB-DNJ inside peripheral blood mononuclear cells were used to increase drug efficacy. RESULTS: NB-DNJ decreased viral infectivity with a single round of treatment by an average of 80% in HIV-1-infected and 95% in HIV-2-infected cultures. Two rounds of treatment reduced viral infectivity to below detectable levels for all isolates tested, with a calculated IC50 of 282 and 211 micromol/l for HIV-1 and HIV-2, respectively. When encapsulated inside liposomes, NB-DNJ inhibited HIV-1 with final concentrations in the nmol/l range (IC50 = 4 nmol/l), a 100 000-fold enhancement in IC50 relative to free NB-DNJ. Targeting liposomes to the gp120/gp41 complex with a CD4 molecule conjugated to the outer bilayer increased drug/liposome uptake five-fold in HIV-infected cells compared with uninfected cells. NB-DNJ CD4 liposomes demonstrated additional antiviral effects, reducing viral secretion by 81% and effectively neutralizing free viral particles to prevent further infections. CONCLUSION: The use of targeted liposomes encapsulating NB-DNJ provides an attractive therapeutic option against all clades of HIV, including drug-resistant isolates, in an attempt to prevent disease progression to AIDS.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Pollock, S., Dwek, R., Burton, D., & Zitzmann, N. (2008). N-Butyldeoxynojirimycin is a broadly effective anti-HIV therapy significantly enhanced by targeted liposome delivery. AIDS (London, England), 22(15), 1961–1969.

MLA Style

Pollock, S., et al. “N-Butyldeoxynojirimycin Is a Broadly Effective Anti-HIV Therapy Significantly Enhanced by Targeted Liposome Delivery.” AIDS (London, England), vol. 22, no. 15, Lippincott, Williams and Wilkins, 2008, pp. 1961–69.

Chicago Style

Pollock, S, R Dwek, D Burton, and N Zitzmann. 2008. “N-Butyldeoxynojirimycin Is a Broadly Effective Anti-HIV Therapy Significantly Enhanced by Targeted Liposome Delivery.” AIDS (London, England) 22 (15): 1961–69.
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