Development and optimization of TPGS-based stealth liposome of doxorubicin using Box-Behnken design: characterization, hemocompatibility, and cytotoxicity evaluation in breast cancer cells

The present work reports the development of doxorubicin (DOX) encapsulated alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated liposomal system (DOX-LIPO-TPGS) by quality by design (QbD) approach and evaluated for its anticancer and hemocompatibility potential. The screening and optimization of formulation variables were performed by the systematic design of experiments (DoE), using Taguchi and Box-Behnken design (BBD) for their desired quality attributes. The QbD optimized DOX-LIPO (DOX encapsulated uncoated liposome) and DOX-LIPO-TPGS formulation showed nano-metric vesicle size (98.2 +/- 3.1 and 117.6 +/- 3.5 nm) with favourable development parameters, i.e. PDI (0.262 +/- 0.008 and 0.123 +/- 0.005); ZP (-38.7 +/- 0.5 and -36.4 +/- 0.7 mV) and % EE (66.8 +/- 3.3 and 73.5 +/- 3.5%) respectively. The release kinetics parameters suggested, sustained release behaviour of developed liposomal formulations (83.6 +/- 2.8 and 69.8 +/- 2.2% releases in 72 h, respectively). Cytotoxicity (MTT assay) on the MCF-7 breast cancer cell line and haemolysis assay on RBCs stipulates comparatively higher anticancer potential and better hemocompatibility of DOX-LIPO-TPGS with respect to DOX-LIPO and the plain DOX solution. The study concluded that the QbD based three levels by three factors BBD optimization could be utilized for obtaining liposomal formulations with desired quality attributes. TPGS could be set out as a vital additive to improve the various quality parameters including stealthing character, stability, kinetic release, cytotoxicity, and hemocompatibility of liposomal formulations. This may serve as a focal paradigm for using TPGS-coated liposomes as anticancer drug delivery vehicle in normal and MDR carcinoma.

Automated summary

This study reports the development of a doxorubicin-loaded liposomal system coated with alpha-tocopherol polyethylene glycol 1000 succinate through a quality by design approach, showing promising anticancer and hemocompatibility potential. Optimization of formulation variables using systematic design of experiments resulted in nano-sized vesicles with favorable development parameters, and the inclusion of TPGS significantly improved the quality attributes of the liposomal formulations. The study concludes that quality by design optimization can be effectively utilized for obtaining liposomal formulations with desired attributes, and TPGS-coated liposomes may serve as an effective anticancer drug delivery vehicle.