title: Polymeric nanoparticles containing combination antiretroviral drugs for HIV type 1 treatment.
abstract: The use of combination antiretroviral nanoparticles (cART NPs) was investigated as a novel treatment approach for the inhibition of HIV-1 replication. We developed nanoparticles of biodegradable polymer, poly-(dl-lactide-co-glycolic acid; PLGA) containing efavirenz (EFV) and boosted lopinavir (lopinavir/ritonavir; LPV/r) by a high-pressure homogenization method. The method resulted in >79% drug entrapment efficiency for each of the three drugs. The average size of cART NPs was 138.3±55.4 nm as measured by dynamic light scanning, confirmed by scanning electron microscopy (SEM) with an average surface charge of -13.7±4.5. Lissamine-rhodamine-labeled fluorescent PLGA NPs exhibited efficient uptake in nonimmune (HeLa cells) and immune (H9 T cells) cells as measured by confocal microscopy. Cells treated with cART NPs resulted in minimal loss of cell viability over 28 days. Subcellular fractionation studies demonstrated that HIV-1-infected H9 monocytic cells treated with cART NPs contained significantly (p<0.05) higher nuclear, cytoskeleton, and membrane antiretroviral drug levels compared to cells treated with drug solutions alone. Finally, cART NPs efficiently inhibited HIV-1 infection and transduction. The IC50 for each of the three drugs in the cART NPs was <31 nM. These experiments demonstrate the efficacy of a novel PLGA NPs formulation for the delivery of cART to inhibit HIV-1 replication.
authors.affiliation: Department of Biology, Creighton University, Omaha, Nebraska, USA.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Shibata
authors.forename: Emily
authors.initials: E
authors.lastname: McMullen
authors.forename: Alex
authors.initials: A
authors.lastname: Pham
authors.forename: Michael
authors.initials: M
authors.lastname: Belshan
authors.forename: Bridget
authors.initials: B
authors.lastname: Sanford
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.forename: Michael
authors.initials: M
authors.lastname: Goede
authors.forename: Abhijit A
authors.initials: AA
authors.lastname: Date
authors.forename: Abjijit A
authors.initials: AA
authors.lastname: Date
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Destache
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D048588:Benzoxazines / Q000008:administration & dosage / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid; D061466:Lopinavir / Q000008:administration & dosage / Q000627:therapeutic use; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000627:therapeutic use*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013347:Subcellular Fractions / Q000378:metabolism; D020298:U937 Cells / Q000378:metabolism
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D061466:Lopinavir; D011100:Polyglycolic Acid; D019344:Lactic Acid; C098320:efavirenz