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

Abstract

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 three months and in PBS at 37°C over 102 hours 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 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.

Development and optimization of oil-filled lipid nanoparticles containing docetaxel conjugates designed to control the drug release rate in vitro and in vivo

“…It should be noted that the general placebo composition for this formulation was previously optimized. 22 Thus, it was anticipated that continued optimization with DX conjugates would lead to a relatively narrow response range. When the model focused on the effect of surfactant concentrations on the percent of entrapment efficiency, it was clear that decreasing the surfactant concentrations increased drug entrapment in the NPs (Figure 3).…”

“…22 Briefly, defined amounts of Miglyol 808 and surfactants (Brij 78 and Vitamin E TPGS) were accurately weighed into glass vials and heated to 50°C-60°C. Drugs dissolved in ACN were added and the organic solvent was removed by nitrogen flow.…”

Improving an Electrostatic Powder Coating Process via Signal to Noise Response Surface

“…The design point with the lowest yield is reflected in the opposite face and the next run is carried out at this point. This idea is not commonly referred to in statistical texts but has received more attention in the chemometrics literature (Dong et al, 2009). They tried various rules for making the algorithm proceed more efficiently without an oscillation or rotating about a design point.…”

Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

“…25 The procedure to prepare RTV NP-containing solid granules is shown in Figure 1A. To prepare NPs suitable for RTV, we used oleic acid as a lipid and TPGS as a surfactant.…”

“…For these purposes, RTV was chosen as the model drug for the studies reported herein. We initiated the NP development using a previously published microemulsionprecursor method, 25 and then converted NPs to solid granules by wet granulation. We refer to this nanoformulation as RTV NP-containing granules ( Figure 1A).…”