Breast cancer remains the second leading cause of cancer deaths for women in the U.S. The
need for new and alternative strategies to treat this cancer is imperative. Here we show the optimization
of our nanochannel delivery system (nDS) for constant and sustained delivery of docetaxel (DTX)
for thetreatment of triple negative breast cancer. DTX is a highly hydrophobic drug, making it difficult
to reach the therapeutic levels when released in aqueous solutions from our implantable delivery system. To overcome this
challenge and test the release of DTX from nDS, we prepared DTX/2-hydroxypropyl β-cyclodextrin (DTX/HPCD) inclusion
complexes in different molar ratios. The 1:10 DTX/HPCD complex achieved 5 times higher solubility than the 1:2
complex and 3 times higher in vitro release of DTX than with free DTX. When released in SCID/Beige mice from nanochannel
system, the DTX/HPCD complex showed reduced tumor growth, comparable to the standard bolus injections of
DTX, indicating that the structural stability and biological activity of DTX were retained in the complex, after its diffusion
through the nanochannel system.
Keywords: Cyclodextrin, docetaxel, drug delivery, inclusion complexes, nanochannel implants, sustained release.
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