Conventional and long-circulating liposomes of artemisinin: preparation, characterization, and pharmacokinetic profile in mice

被引:78
作者
Isacchi, Benedetta [1 ]
Arrigucci, Silvia [2 ]
la Marca, Giancarlo [2 ,3 ]
Bergonzi, Maria Camilla [1 ]
Vannucchi, Maria Giuliana [4 ]
Novelli, Andrea [2 ]
Bilia, Anna Rita [1 ]
机构
[1] Univ Florence, Dept Pharmaceut Sci, I-50019 Florence, Italy
[2] Univ Florence, Dept Preclin & Clin Pharmacol, I-50019 Florence, Italy
[3] AUO Meyer, Mass Spectrometry Clin Chem & Pharmacol Lab, Florence, Italy
[4] Univ Florence, Sect Histol, Dept Anat Histol & Forens Med, I-50019 Florence, Italy
关键词
Artemisinin; conventional liposomes; PEGylated liposomes; pharmacokinetic properties in mice; INCLUSION COMPLEXATION; BETA-CYCLODEXTRIN; LIPID-COMPOSITION; BREAST-CANCER; INTRAPERITONEAL; MALARIA; DIHYDROARTEMISININ; ARTEMETHER; INJECTION; HYDRATION;
D O I
10.3109/08982104.2010.539185
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Artemisinin (qinghaosu), a unique endoperoxide sesquiterpene lactone isolated from Artemisia annua L., is a very active antimalarial drug, including severe and cerebral malaria. However, its therapeutical efficacy is limited due to its scarce bioavailability. In this article, artemisinin-loaded conventional and polyethylene glycol (PEGylated) liposomes were proposed as carriers to increase biopharmaceutical properties of the drug. Encapsulation efficacy was determined by high-performance liquid chromatography/diode array detection/electrospray ionization-mass spectrometry, dimensional analysis was performed by dynamic light scattering, and morphology was performed by trasmission electron microscopy. After dialysis, both liposomal formulations showed an encapsulation efficacy of more than 70%; mean diameter of all the artemisinin-loaded vesicles was approximately 130-140 nm. The polydispersity index of the formulations ranged from 0.2 to 0.3 and resulted as suitable for intraperitoneal (i.p.) administration. Pharmacokinetic profile and the main pharmacokinetic parameters of the carriers were evaluated in healthy mice i.p. Free artemisinin was rapidly cleared from plasma and hardly detected 1 hour after administration. Conversely, both liposomal formulations showed much longer blood-circulation time than free artemisinin; artemisinin was still detectable after 3 and 24 hours of administration, respectively, for conventional and PEGylated liposomes. AUC(0-24h) values were increased by approximately 6 times in both of the liposomal formulations, in comparison with free artemisinin. A strong effect of formulation on the half-life of artemisinin was enhanced by more than 5-fold by the incorporation of PEG into liposomes. Liposomes loaded with artemisinin, especially the long-circulating vesicles, could really represent a new strategy for developing smart, well-tolerated, and efficacious therapeutic nanocarriers to treat tumors, but could also be very useful to treat parasitic disease.
引用
收藏
页码:237 / 244
页数:8
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