title: Targeting primaquine into liver using chylomicron emulsions for potential vivax malaria therapy.
abstract: Primaquine (PQ) exerts a broad spectrum of activities against various stages of parasitic malaria. It remains as the only drug that destroys late hepatic stages and latent tissue forms of Plasmodium vivax and Plasmodium ovale. However, systems that can target PQ to liver hepatocytes, where malarial sporozoites reside, are needed to minimize the dose-limiting severe toxicities and side-effects caused by PQ. Recently, a reconstituted artificial chylomicron emulsion was generated using commercially available lipids and was shown to be preferentially taken up by liver hepatocytes following intravenous injection. We proposed to target PQ to hepatocytes by incorporating it into this chylomicron emulsion. We have shown that lipophilized PQ can be readily incorporated into the chylomicron emulsion. The PQ remained inside the emulsion without significant release. Moreover, PQ incorporated inside the emulsion was more stable than free PQ when incubated in serum. Finally, when intravenously injected into mice, the PQ-incorporated chylomicron emulsion led to significantly enhanced accumulation of PQ in liver, when compared to the injection of free PQ. This emulsion could be developed into a promising delivery system to target PQ into hepatocytes for vivax malaria therapy.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Dierling
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002914:Chylomicrons / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions / Q000138:chemical synthesis; D005612:Freeze Drying; D007275:Injections, Intravenous; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D016780:Malaria, Vivax / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011319:Primaquine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D000962:Antimalarials; D002914:Chylomicrons; D004655:Emulsions; D011319:Primaquine