Development of new lipid-based paclitaxel nanoparticles using sequential simplex optimization

Xiaowei Dong, Cynthia A. Mattingly, Michael Tseng, Moo Cho, Val R. Adams, Russell J. Mumper

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


The objective of these studies was to develop Cremophor-free lipid-based paclitaxel (PX) nanoparticle formulations prepared from warm microemulsion precursors. To identify and optimize new nanoparticles, experimental design was performed combining Taguchi array and sequential simplex optimization. The combination of Taguchi array and sequential simplex optimization efficiently directed the design of paclitaxel nanoparticles. Two optimized paclitaxel nanoparticles (NPs) were obtained: G78 NPs composed of glyceryl tridodecanoate (GT) and polyoxyethylene 20-stearyl ether (Brij 78), and BTM NPs composed of Miglyol 812, Brij 78, and d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both nanoparticles successfully entrapped paclitaxel at a final concentration of 150 μg/ml (over 6% drug loading) with particle sizes less than 200 nm and over 85% of entrapment efficiency. These novel paclitaxel nanoparticles were stable at 4 °C over five months and in PBS at 37 °C over 102 h as measured by physical stability. Release of paclitaxel was slow and sustained without initial burst release. Cytotoxicity studies in MDA-MB-231 cancer cells showed that both nanoparticles have similar anticancer activities compared to Taxol®. Interestingly, PX BTM nanocapsules could be lyophilized without cryoprotectants. The lyophilized powder comprised only of PX BTM NPs in water could be rapidly rehydrated with a complete retention of original physicochemical properties, in vitro release properties, and cytotoxicity profile. Sequential Simplex Optimization has been utilized to identify promising new lipid-based paclitaxel nanoparticles having useful attributes.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number1
StatePublished - May 2009

Bibliographical note

Funding Information:
This research was supported by NIH-NCI R01 CA115197 to R.J.M., V.A., and M.T.


  • Cancer
  • Cytotoxicity
  • Experimental design
  • Lyophilization
  • Nanocapsule

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science


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