Lipid-derivatized poly(ethylene glycol) micellar formulations of benzoporphyrin derivatives
In this paper, we describe the development of micellar formulations for increasing the solubility of lipophilic benzoporphyrins. Using a simple procedure that is readily adaptable for large-scale manufacturing, both A-ring ( 1) and B-ring isomers ( 2) of benzoporphyrins could be readily formulated,...
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Published in | Journal of controlled release Vol. 86; no. 2; pp. 323 - 338 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier B.V
17.01.2003
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | In this paper, we describe the development of micellar formulations for increasing the solubility of lipophilic benzoporphyrins. Using a simple procedure that is readily adaptable for large-scale manufacturing, both A-ring (
1) and B-ring isomers (
2) of benzoporphyrins could be readily formulated, at concentrations up to 1–2 mg/ml, into small micelles (<20 nm in diameter) of methoxypoly(ethylene glycol) (
M
r 2000) covalently attached to the lipid anchor distearoylphosphatidylethanolamine (mPEG-DSPE). The formulations spontaneously formed upon hydration of a thin film containing mPEG-lipid and photosensitizer and were stable upon storage at 4
°C for at least 1 month. Self-association of the B-ring benzoporphyrin isomer in micelles could be efficiently inhibited by either increasing the molar ratio of mPEG
2000-DSPE to benzoporphyrin or by increasing the pH of the preparation to pH 8.5. The formulation could be freeze-dried and stored indefinitely in the lyophilized form, with restoration of the original properties upon reconstitution. In vivo, the A-ring benzoporphyrin, verteporfin, had higher levels of delivery and greater tumor control in mice than the B-ring derivative when formulated in mPEG
2000-DSPE micelles and administered intravenously. mPEG
2000-DSPE micellar formulations also showed tumor control when administered by a single intratumoral injection followed by light irradiation to the tumor within 45–60 min after drug administration. PEG-containing micellar formulations may be a promising delivery system for benzoporphyrin monoesters for clinical applications. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0168-3659 1873-4995 |
DOI: | 10.1016/S0168-3659(02)00442-X |