Antiretroviral release from poly(DL-lactide-co-glycolide) nanoparticles in mice

Research output: Contribution to journalArticle

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Abstract

Objectives: Free ritonavir, lopinavir and efavirenz injected intraperitoneally were compared with antiretroviral (AR) nanoparticles (NPs). Methods: This is a prospective study in BALB/c mice comparing the pharmacokinetics of free drugs with AR NPs. All animals received free drugs or AR NPs (20 mg/kg) in PBS. In vitro replication assays were used for determination of the anti-HIV efficacy of NP formulations. At specific times (free drugs 0.08, 0.125, 0.25, 0.33, 1, 2 and 3 days; AR NPs 0.125, 0.33, 1, 2, 4, 7, 14, 21, 28, 35 and 42 days) mice were euthanized and serum and organs were harvested for determination of AR concentrations by HPLC. Single treatment of monocyte-derived macrophages (MDMs) infected with HIV-1 ada compared AR NPs (0.005-0.05 mg/mL) with free efavirenz or lopinavir/ritonavir (0.01-0.1 mg/mL), blank NPs and controls. Results are presented as means±SEM. Results: Serum free AR drug concentrations peaked 4 h post-injection (ritonavir 3.9±3.05, lopinavir 3.4±2.5 and efavirenz 1.8±0.63 μg/mL) and were eliminated by 72 h. Poly( DL-lactide-co-glycolide) NP animals had detectable ritonavir, lopinavir and efavirenz concentrations in all tissues for 28 days. Treatment of MDMs with AR NPs resulted in sustained inhibition of HIV-1 ada replication. Conclusions: AR drug concentrations from NPs are sustained for 28 days in vivo and anti-HIV inhibition was comparable to that of free drugs in vitro and could be a sustained treatment for delivery of AR drugs.

Original languageEnglish
Article numberdkq318
Pages (from-to)2183-2187
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume65
Issue number10
DOIs
StatePublished - Aug 21 2010

Fingerprint

Polyglactin 910
Nanoparticles
efavirenz
Lopinavir
Ritonavir
Pharmaceutical Preparations
HIV-1
Macrophages
poly(lactide)
HIV
Serum
Therapeutics
Pharmacokinetics
High Pressure Liquid Chromatography
Prospective Studies

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Antiretroviral release from poly(DL-lactide-co-glycolide) nanoparticles in mice. / Destache, Christopher J.; Belgum, Todd; Goede, Michael; Shibata, Annemarie; Belshan, Michael A.

In: Journal of Antimicrobial Chemotherapy, Vol. 65, No. 10, dkq318, 21.08.2010, p. 2183-2187.

Research output: Contribution to journalArticle

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abstract = "Objectives: Free ritonavir, lopinavir and efavirenz injected intraperitoneally were compared with antiretroviral (AR) nanoparticles (NPs). Methods: This is a prospective study in BALB/c mice comparing the pharmacokinetics of free drugs with AR NPs. All animals received free drugs or AR NPs (20 mg/kg) in PBS. In vitro replication assays were used for determination of the anti-HIV efficacy of NP formulations. At specific times (free drugs 0.08, 0.125, 0.25, 0.33, 1, 2 and 3 days; AR NPs 0.125, 0.33, 1, 2, 4, 7, 14, 21, 28, 35 and 42 days) mice were euthanized and serum and organs were harvested for determination of AR concentrations by HPLC. Single treatment of monocyte-derived macrophages (MDMs) infected with HIV-1 ada compared AR NPs (0.005-0.05 mg/mL) with free efavirenz or lopinavir/ritonavir (0.01-0.1 mg/mL), blank NPs and controls. Results are presented as means±SEM. Results: Serum free AR drug concentrations peaked 4 h post-injection (ritonavir 3.9±3.05, lopinavir 3.4±2.5 and efavirenz 1.8±0.63 μg/mL) and were eliminated by 72 h. Poly( DL-lactide-co-glycolide) NP animals had detectable ritonavir, lopinavir and efavirenz concentrations in all tissues for 28 days. Treatment of MDMs with AR NPs resulted in sustained inhibition of HIV-1 ada replication. Conclusions: AR drug concentrations from NPs are sustained for 28 days in vivo and anti-HIV inhibition was comparable to that of free drugs in vitro and could be a sustained treatment for delivery of AR drugs.",
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