Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases.
BACKGROUND
In this investigation, the antileukemic activity of a new nanomedicine based on the conjugation of 1,1',2-tris-nor-squalenic acid with cytarabine (Ara-C) was evaluated.


METHODS
Squalenoyl-Ara-C conjugate (Sq-Ara-C) self-assembled nanosystems were obtained by the nanoprecipitation method and characterized in vitro and in vivo.


RESULTS
This new nanomedicine, which had a mean diameter of approximately 150 nm, improved the in vitro antitumoral activity of Ara-C in different cancer cell lines (L1210, K562, and MCF-7). Sq-Ara-C nanomedicine allowed reduction of the IC(50) value with respect to the free drug and was also active against drug-resistant leukemic cells (L1210R). A noticeable increase in the survival rate of mice with aggressive metastatic L1210R leukemia was observed after treatment with Sq-Ara-C (50 mg/kg) as compared with the free active compound (100 mg/kg). Finally, evaluation of the biodistribution and pharmacokinetic profiles of the drug demonstrated that these nanoaggregates preferentially localized to the liver and spleen, and protected the drug from physiological metabolism.


CONCLUSIONS
Squalenoylation of cytarabine offers several pharmacological benefits both in vitro and in vivo.
Department of Health Sciences, University Magna Græcia, Catanzaro, Italy.
Donato
D
Cosco
Flavio
F
Rocco
Maurizio
M
Ceruti
Margherita
M
Vono
Massimo
M
Fresta
Donatella
D
Paolino
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013154:Spleen / Q000737:chemistry; D013185:Squalene / Q000008:administration & dosage / Q000737:chemistry*; D016019:Survival Analysis; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D003561:Cytarabine; D013185:Squalene