Catanionic lipid nanosystems improve pharmacokinetics and anti-lung cancer activity of curcumin

doi:10.1016/j.nano.2016.02.007

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 12, Issue 6, August 2016, Pages 1567-1579

https://doi.org/10.1016/j.nano.2016.02.007 Get rights and content

Abstract

Novel catanionic lipid nanosystems (CLNs) incorporating curcumin (CCM) were developed, and improvements in pharmacokinetics and enhanced anti-lung cancer activity were observed. CCM was present in a lipid matrix surrounded by cationic, anionic and zwitterionic surfactants, forming the core-shell nanosystems. Compared with free CCM, the CCM-CLNs had much higher oral and intravenous bioavailabilities due to enhanced absorption and reduced clearance. The CCM-CLNs exhibited greater cytotoxicity in Lewis lung cancer (LLC) cells, which might have been due to increased antiproliferative, proapoptotic and anti-invasive activities and induction of cell cycle arrest. The CCM-CLNs increased the antitumor efficacy of CCM and decreased the tumor growth rate in tumor-bearing mice. This is the first report of induction of apoptosis in LLC cells by CCM through the PI3K/Akt/FoxO1/Bim signaling pathway. Catanionic lipid nanocarriers show promise for the therapeutic delivery of insoluble anti-tumor drugs.

Graphical abstract

A class of novel catanionic lipid nanosystems loaded with CCM (CCM-CLNs) was developed for the efficient delivery of CCM. Compared with free CCM, CCM-CLNs exhibited significant improvements in pharmacokinetics and bioavailability, as well as a substantial increase in anti-lung cancer activity. This is the first report of induction of apoptosis in LLC cells by CCM through the PI3K/Akt/FoxO1/Bim signaling pathway. Catanionic lipid nanocarriers show promise for the therapeutic delivery of insoluble anti-tumor drugs.

Section snippets

Methods

All animal experiments were performed in accordance with the protocol approved by the Laboratory Animal Committee of Third Military Medical University.

Preparation and formulation optimization of CCM-CLNs

The CCM-CLNs consisted of glycerin monostearate (solid lipid), the catanionic surfactants CTAB (cationic surfactant) and SDS (anionic surfactant), and soybean phospholipid (emulsifier and zwitterionic surfactant) (Figure 1, A). The CCM-CLNs were successfully prepared with high entrapment (97.57 ± 2.55%, n = 3) and drug loading efficiencies (3.49 ± 0.11%, n = 3). The Box-Behnken design was applied to optimize the formulation of the CCM-CLNs (Figure 1, B). The entrapment and drug loading efficiencies of

Discussion

CCM is potentially useful for the prevention and treatment of cancer. However, its clinical application has been severely hindered by its undesirable solubility, low bioavailability, lack of availability to tumors and poor tumor cellular uptake. Recently, application of lipid-based nanosystems for drug delivery has become a popular research area. For example, lipid nanoparticles have been used to carry oryzalin for the treatment of leishmaniasis,²² and to co-deliver rapamycin and quantum dots

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: The authors declare no conflict of interest statement/financial support.

: This research was partially supported by grants from Chongqing Science and Technology Committee (cstc2015jcyjBX0027) and Chongqing Education Committee Fund (Excellent university personnel financial aid plan, KJ120321).

¹: These authors contributed equally to this work.

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Original ArticleCatanionic lipid nanosystems improve pharmacokinetics and anti-lung cancer activity of curcumin

Abstract

Graphical abstract

Section snippets

Methods

Preparation and formulation optimization of CCM-CLNs

Discussion

Cancer Lett

Eur J Cancer

Eur J Pharm Biopharm

Eur J Pharm Biopharm

Biomaterials

Eur J Pharm Sci

J Colloid Interface Sci

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Original Article
Catanionic lipid nanosystems improve pharmacokinetics and anti-lung cancer activity of curcumin