Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 49, Pages 42186-42197Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b18979
Keywords
chemotherapy; hydrogen bonding; oral delivery; poly(N-vinylpyrrolidone); paclitaxel; tannic acid
Funding
- Guangdong Innovative and Entrepreneurial Research Team Program [2013S086]
- Natural Science Foundation of China [51820105004, 51803243]
- Natural Science Foundation of Guangdong Province [2014A030312018]
- Fundamental Research Funds for the Central Universities [17lgpy06]
- Shenzhen Scientific Technology Research Program [JCYJ20160520170646118, JCYJ20170817100035677]
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Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Currently, nanoparticulate drug delivery systems (NDDS) exhibit many unique advantages in mediating oral drug delivery; however, many anticancer drugs that were susceptible in hostile gastrointestinal (GI) environment showed poor permeability across intestinal epithelium, and most materials used as drug carriers are nonactive excipients and displayed no therapeutically relevant function, which leads to low oral bioavailability and therapeutic efficacy of anticancer drugs (e.g., paclitaxel). Inspired by these, in this study, paclitaxel (PTX) was used as a model drug, depending on intermolecular hydrogen-bonded interactions, PTX-loaded tannic acid/poly(N-vinylpyrrolidone) nanoparticles (PTX-NP) were produced by a flash nanoprecipitation (FNP) process. The optimized PTX-NP showed an average diameter of 54 nm with a drug encapsulation efficiency of 80% and loading capacity of 14.5%. Molecular dynamics simulations were carried out to illuminate the assembling mechanism of hydrogen-bonded PTX-NP. In vitro and in vivo results confirmed that PTX-NP showed pH-dependent intestinal site-specific drug release, P-gp inhibitory function by tannic acid (TA), prolonged intestinal retention, and improved trans-epithelial transport properties. Oral administration of PTX-NP generated a high oral delivery efficiency and relative oral bioavailability of 25.6% in rats, and further displayed a significant tumor-inhibition effect in a xenograft breast tumor model. These findings confirmed that our PTX-NP might be a promising oral drug formulation for chemotherapy.
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