Novel temperature-triggered liposome with high stability: formulation, in vitro evaluation, and in vivo study combined with high-intensity focused ultrasound (HIFU).
J Control Release
; 170(3): 373-9, 2013 Sep 28.
Article
em En
| MEDLINE
| ID: mdl-23770213
ABSTRACT
We developed a novel temperature-sensitive liposome, STL composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG-2000), cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP). The STL had a unilamellar spherical shape with a mean diameter of 160 nm. Doxorubicin (DOX) was encapsulated by the STL using an ammonium sulfate gradient method with a lipid to drug ratio of 10.2 (w/w), resulting in 95% loading efficiency. The STL exhibited better stability than conventional low temperature sensitive liposome (LTSL-lysolipid-based temperature sensitive liposomes; DPPCMSPCDSPE-PEG-2000=90104) at 37 °C in the presence of serum; there was rapid release of doxorubicin in the range of 39-42 °C (≥95% release at 42 °C within 10s). A confocal microscope revealed that DOX encapsulated in STL (STL-DOX) was taken up much better by cell nuclei at 42 °C than at 37 °C. The difference in cell viability between 37 and 42 °C was 63% relative to STL-DOX and 18% for LTSL-DOX. The pharmacokinetics (PK) and antitumor effect of STL-DOX combined with high-intensity focused ultrasound (HIFU) were studied, and compared with LTSL. An in vivo study demonstrated that STL-DOX is highly stable, with a long circulating property (half life=2.03±0.77 h) in HIFU-untreated mice, and resulted in significant tumor regression for 2 days after intravenous injection of STL-DOX at 5 mg DOX/kg in combination with HIFU. These results are better than conventional LTSL, for which the blood circulation time is short (0.92±0.17 h) and inhibition of tumor growth is weak. These results indicate that the properties of stability at 37 °C and burst release at 42 °C of STL-DOX act synergistically against tumors.
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MEDLINE
Assunto principal:
Doxorrubicina
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Ablação por Ultrassom Focalizado de Alta Intensidade
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Antibióticos Antineoplásicos
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Neoplasias
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article