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In vivo characterization of a polymeric nanoparticle platform with potential oral drug delivery capabilities
Ist Teil von
Molecular cancer therapeutics, 2008-12, Vol.7 (12), p.3878-3888
Ort / Verlag
United States: American Association for Cancer Research
Erscheinungsjahr
2008
Quelle
MEDLINE
Beschreibungen/Notizen
Nanotechnology has enabled significant advances in the areas of cancer diagnosis and therapy. The field of drug delivery is
a sterling example, with nanoparticles being increasingly used for generating therapeutic formulations of poorly water-soluble,
yet potent anticancer drugs. Whereas a number of nanoparticle-drug combinations are at various stages of preclinical or clinical
assessment, the overwhelming majorities of such systems are injectable formulations and are incapable of being partaken orally.
The development of an oral nano-delivery system would have distinct advantages for cancer chemotherapy. We report the synthesis
and physicochemical characterization of orally bioavailable polymeric nanoparticles composed of N -isopropylacrylamide, methylmethacrylate, and acrylic acid in the molar ratios of 60:20:20 (designated NMA622). Amphiphilic
NMA622 nanoparticles show a size distribution of <100 nm (mean diameter of 80 ± 34 nm) with low polydispersity and can readily
encapsulate a number of poorly water-soluble drugs such as rapamycin within the hydrophobic core. No apparent systemic toxicities
are observed in mice receiving as much as 500 mg/kg of the orally administered void NMA622 for 4 weeks. Using NMA622-encapsulated
rapamycin (“nanorapamycin”) as a prototype for oral nano-drug delivery, we show favorable in vivo pharmacokinetics and therapeutic efficacy in a xenograft model of human pancreatic cancer. Oral nanorapamycin leads to robust
inhibition of the mammalian target of rapamycin pathway in pancreatic cancer xenografts, which is accompanied by significant
growth inhibition ( P < 0.01) compared with control tumors. These data indicate that NMA622 nanoparticles provide a suitable platform for oral
delivery of water-insoluble drugs like rapamycin for cancer therapy. [Mol Cancer Ther 2008;7(12):3878–88]