Mixed micelles made of poly(ethylene glycol)-phosphatidylethanolamine conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate as pharmaceutical nanocarriers for camptothecin

Abstract

Micelles from the mixture of poly(ethylene glycol)-phosphatidyl ethanolamine conjugate (PEG-PE) and d-alpha-tocopheryl polyetheyene glycol 1000 succinate (TPGS) were prepared loaded with the poorly soluble anticancer drug camptothecin (CPT). The solubilization of CPT by the mixed micelles was more efficient than with earlier described micelles made of PEG-PE alone. CPT-loaded mixed micelles were stable upon storage and dilution and firmly retained the incorporated drug. The cytotoxicity of the CPT-loaded mixed micelles against various cancer cells in vitro was remarkably higher than that of the free drug. PEG-PE/TPGS mixed micelles may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

Fig. 1

HPLC profile of CPT-loaded PEG-PE/TPGS micelles.

Fig. 2

PEG-PE/TPGS micelle size and size distribution pattern during incubation at 37 °C and 100 rpm shaking (A: before incubation; B: after 24 h incubation; C: after 48 h incubation).

Fig. 3

Mean diameters of CPT-loaded PEG-PE/TPGS micelles at various molar concentrations of Na salicylate in aqueous solution after one week long incubation.

Fig. 4

Release profile of CPT from PEG-PE/TPGS micelles (▲) in 1.0 M aqueous Na salicylate at 37 °C; CPT-loaded micelles made of PEG-PE alone (□) were used for comparison.

Fig. 5

In vitro cytotoxicity of free CPT (▲) and of CPT-free (•) and CPT-loaded (○ mixed PEG-PE/TPGS micelles against various cancer cell lines (A: LLC1 cells; B: MCF7 cells; C: HT29 cells).