Nanoprodrugs of NSAIDs: Preparation and Characterization of Flufenamic Acid Nanoprodrugs

被引：13

作者：

Lee, Bong-Seop ^{[1
]}

Yoon, ChiWoo ^{[1
]}

Osipov, Arsen ^{[1
]}

Moghavem, Nuriel ^{[1
]}

Nwachokor, Daniel ^{[1
]}

Amatya, Rina ^{[1
]}

Na, Rebekah ^{[1
]}

Pantoja, Joe L. ^{[1
]}

Pham, Michael D. ^{[1
]}

Black, Keith L. ^{[1
]}

Yu, John S. ^{[1
]}

机构：

[1] Cedars Sinai Med Ctr, Dept Neurosurg, 8631 West Third St,Suite 800 East, Los Angeles, CA 90048 USA

来源：

JOURNAL OF DRUG DELIVERY | 2011年 / 2011卷

关键词：

D O I：

10.1155/2011/980720

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We demonstrated that hydrophobic derivatives of the nonsteroidal anti-inflammatory drug (NSAID) flufenamic acid (FA), can be formed into stable nanometer-sized prodrugs (nanoprodrugs) that inhibit the growth of glioma cells, suggesting their potential application as anticancer agent. We synthesized highly hydrophobic monomeric and dimeric prodrugs of FA via esterification and prepared nanoprodrugs using spontaneous emulsification mechanism. The nanoprodrugs were in the size range of 120 to 140nm and physicochemically stable upon long-termstorage as aqueous suspension, which is attributed to the strong hydrophobic interaction between prodrug molecules. Importantly, despite the highly hydrophobic nature and water insolubility, nanoprodrugs could be readily activated into the parent drug by porcine liver esterase, presenting a potential new strategy for novel NSAID prodrug design. The nanoprodrug inhibited the growth of U87-MG glioma cells with IC50 of 20 aeM, whereas FA showed IC50 of 100 aeM, suggesting that more efficient drug delivery was achieved with nanoprodrugs.

引用

页数：13

共 45 条

[21] CORRELATIONS BETWEEN LIQUID-CHROMATOGRAPHIC CAPACITY RATIO DATA ON LICHROSORB-RP-18 AND PARTITION-COEFFICIENTS IN THE OCTANOL WATER-SYSTEM [J].