ABSTRACT
Purpose
To incorporate phospho-ibuprofen (P-I), a lipophilic, water insoluble novel anti-cancer agent, into pegylated liposomes and upon formulation optimization to evaluate its antitumor activity in vitro and in vivo.
Methods
P-I loaded liposomes were prepared using the thin-film hydration method, and characterized for size, zeta potential, drug content and drug release. We examined their physical stability by particle size changes; their lyophilization ability in the presence of cryoprotectants; and their antitumor activity in vitro in human cancer cell lines and in vivo in a xenograft murine model.
Results
P-I was successfully loaded into liposomes consisting of soy-PC and PEG2000-PE. These liposomes were <150 nm in diameter; exhibited prolonged stability in suspension and can be lyophilized using sucrose as cryoprotectant. P-I liposomes inhibited the growth of human cancer cell lines in vitro and in vivo of xenograft in nude mice to a greater extent than free P-I.
Conclusions
High levels of P-I can be incorporated into liposomes which can be lyophilized in the presence of sucrose and showed good stability upon storage. Moreover, these drug-incorporating liposomes were capable of inhibiting the growth of xenografted tumors in mice more effectively than free P-I. These results justify further development of the P-I liposomes.
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Abbreviations
- EE:
-
entrapment efficiency
- egg-PC:
-
egg-phosphatidylcholine
- P-I:
-
phospho-ibuprofen
- RES:
-
recticuloendothelial system
- soy-PC:
-
soy-phosphatidylcholine
- soy-PE:
-
soy-phosphatidylethanolamine
- soy-PS:
-
soy-phosphatidylserine
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ACKNOWLEDGMENTS & DISCLOSURES
Financial support was from NIH grant HHSN261201000109C.
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Mattheolabakis, G., Nie, T., Constantinides, P.P. et al. Sterically Stabilized Liposomes Incorporating the Novel Anticancer Agent Phospho-Ibuprofen (MDC-917): Preparation, Characterization, and In Vitro/In Vivo Evaluation. Pharm Res 29, 1435–1443 (2012). https://doi.org/10.1007/s11095-011-0619-y
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DOI: https://doi.org/10.1007/s11095-011-0619-y