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Colloids and Surfaces B: Biointerfaces 2017-Jul

P-gp modulatory acetyl-11-keto-β-boswellic acid based nanoemulsified carrier system for augmented oral chemotherapy of docetaxel.

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Gitu Pandey
Naresh Mittapelly
Guru Raghavendra Valicherla
Ravi Prakash Shukla
Shweta Sharma
Venkatesh Teja Banala
Sandeep Urandur
Arun Kumar Jajoriya
Kalyan Mitra
D P Mishra

Nøgleord

Abstrakt

In spite of being a very potent and promising drug against many types of cancer, docetaxel suffers the disadvantage of low solubility and poor bioavailability rendering it unsuitable for oral administration. Also, the available marketed formulation for intravenous administration has its inherent drawbacks owing to the presence of polysorbate 80. Here, we exploited the anticancer and P-gp inhibitory potential of naturally occurring frankincense oil to fabricate a stable docetaxel loaded nanoemulsified carrier system for oral delivery. The nanoemulsion possessing desirable particle size (122±12nm), polydispersity (0.086±0.007) and zeta potential (-29.8±2.1mV) was stable against all type of physical stresses and simulated physiological conditions tested. The formulation showed higher uptake in Caco-2 cells and inhibited P-gp transporter significantly (P<0.05). In MDA-MB-231 cells, it showed less IC50, arrested cells in G2-M phase and exhibited higher degree of apoptosis than marketed formulation Taxotere®. The 182.58±4.16% increment in relative oral bioavailability led to higher in vivo anti-proliferative activity manifesting 19% more inhibition than Taxotere®. Conclusively, it is revealed that the developed nanoemulsion will be a propitious approach towards alternative docetaxel therapy.

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