Human scleral diffusion of anticancer drugs from solution and nanoparticle formulation.
Pharm Res
; 26(5): 1155-61, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19194787
ABSTRACT
PURPOSE:
To determine the transscleral permeability of chemotherapeutic drugs vinblastine and doxorubicin for treatment of intraocular tumors, and to compare the use of doxorubicin encapsulated in PLGA and liposome nanoparticles.METHODS:
Human sclera was isolated and mounted in a Lucite chamber. Fluorescently tagged vinblastine (VIN), innately fluorescent free doxorubicin (DOX), PLGA doxorubicin (PLGA-DOX), or Doxil (Tibotec Therapeutics) were added to the episcleral donor chamber. The choroidal side was perfused with Balanced Salt Solution. Perfusate fractions were collected over 24 h and measured for fluorescence. Following the experiment, tissue sections were imaged, underwent a drug wash out procedure, and tissue drug content was analyzed using an LC-MS/MS method.RESULTS:
Within 24 h, a total of 68%, 74%, 29%, and 1.9% of the drug dose from VIN, DOX, PLGA-DOX, and Doxil, respectively, diffused across the sclera. VIN and DOX scleral tissue showed strong fluorescence after 24 h. PLGA-DOX displayed scattered fluorescence, and Doxil indicated minimal fluorescence. LC-MS/MS revealed strong tissue binding of DOX.CONCLUSIONS:
This study suggests both vinblastine and doxorubicin are able to diffuse across human sclera. In addition, PLGA nanoparticles delivered doxorubicin at a slower rate across the sclera, and the liposome preparation resulted in the slowest delivery of drug.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Poliglicólico
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Esclera
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Vimblastina
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Doxorrubicina
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Ácido Láctico
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Nanopartículas
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Lipossomos
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Antineoplásicos
Limite:
Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos