Polymer-lipid hybrid nanoparticles synchronize pharmacokinetics of co-encapsulated doxorubicin-mitomycin C and enable their spatiotemporal co-delivery and local bioavailability in breast tumor

Nanomedicine : Nanotechnology, Biology, and Medicine
Rui Xue ZhangXiao Yu Wu

Abstract

Effective combination chemotherapy requires the delivery of drugs of synergism to tumor sites while sparing normal tissues. Herein we investigated whether coencapsulation of doxorubicin and mitomycin C within polymer-lipid hybrid nanoparticles (DMPLN) achieved this goal via ratiometric drugs in an orthotopic murine breast tumor model with nanocarrier-modified biodistribution, pharmacokinetics, local bioavailability and toxicity. Fluorescence imaging revealed quickened and extended tumor uptake but reduced cardiac accumulation of DMPLN. Quantitative drug analysis demonstrated prolonged systemic circulation, increased tumor accumulation and sustained synergistic ratios of doxorubicin and mitomycin C delivered by DMPLN over 24h. Higher levels of tumor cell apoptosis and reduced organ toxicity were obtained with DMPLN compared to free drug cocktails. DMPLN released DOX in tumors more efficiently than that from liposomal doxorubicin, as evidenced by a higher extent of the metabolite, doxorubicinol. These findings substantiate the importance of rational design of nanoparticles for synergistic drug combination therapy. The treatment of cancer usually involves using combination chemotherapeutic agents. In adopting a nanomedicine approa...Continue Reading

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Citations

Mar 16, 2016·Expert Opinion on Drug Delivery·Xiao Yu Wu
Jun 12, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rui Xue ZhangXiao Yu Wu
Nov 5, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yousheng ZhouXiao Yu Wu
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