Cholic Acid-Based Novel Micellar Nanoplatform for Delivering FDA-Approved Taxanes

Abstract

Aim: To structurally modify our existing cholic acid (CA)-based telodendrimer (TD; PEG^5K-CA₈) for effective micellar nanoencapsulation and delivery of the US FDA-approved members of taxane family. Materials & methods: Generation of hybrid TDs was achieved by replacing four of the eight CAs with biocompatible organic moieties using solution-phase peptide synthesis. Drug loading was done using the standard evaporation method. Results: Hybrid TDs can generate micelles with narrow size distributions, low critical micelle concentration values (1–6 μM), better hematocompatibility and lack of in vitro cytotoxicity. Conclusion: Along with PEG^5K-CA₈, CA-based hybrid nanoplatform is the first of its kind that can stably encapsulate all three FDA-approved taxanes with nearly 100% efficiency up to 20% (w/w) loading.

Keywords:

• cabazitaxel
• cholic acid
• docetaxel
• drug delivery
• micelle
• nanoparticle
• paclitaxel
• taxane
• telodendrimer

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Financial & competing interests disclosure

The authors thank NIH for the funding support: 3R01CA115483, 1U01CA198880-01 to KS Lam and 5R01CA199668 to Y Li. G Bharadwaj, Y Li and KS Lam are the inventors of a pending patent on hybrid TDs (US Patent Application no. 62/395,237). KS Lam is the founding scientist of LamnoTherapeutics, Inc., which plan to develop the nanotherapeutics described in the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animals were kept under pathogen-free conditions according to AAALAC guidelines. All animal experiments were performed in compliance with institutional guidelines and according to protocol approved by the Animal Use and Care Administrative Advisory Committee at the University of California, Davis. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.