Development and in vitro evaluation of a novel lipid nanocapsule formulation of etoposide

作者：Saliou Benjamin; Thomas Olivier; Lautram Nolwenn; Clavreul Anne; Hureaux Jose; Urban Thierry; Benoit Jean Pierre; Lagarce Frederic^*

来源：European Journal of Pharmaceutical Sciences, 2013, 50(2): 172-180.

DOI：10.1016/j.ejps.2013.06.013

• Lipid nanocapsules
• Etoposide
• Scale-up
• Cancer
• Chemotherapy
• Nanomedicine

Small cell lung cancer (SCLC) is the most aggressive carcinoma in thoracic oncology, unfortunately, despite chemotherapy, relapse is constant. The effect of etoposide, a major drug used against SCLC, can potentially be enhanced after its encapsulation in nanocarriers. The aim of this study was to use the technology of lipid nanocapsules (LNCs) to obtain nanocarriers with drug loadings compatible with clinical use and with an industrial process. Solubility studies with different co-solvent were first performed, then several process were developed to obtain LNCs. LNCs were then characterized (size, zeta potential, and drug loading). The best formulation called Omega-LNCs had a size of 54.1 +/- 2.0 nm and a zeta potential of -5.8 +/- 3.5 mV and a etoposide drug loading of 5.7 +/- 0.3 mg/g. The characteristics of this formulation were maintained after freeze drying and after a 15 x scale-up. Release studies in a media mimicking plasma composition showed that 40% of the drug was released from the LNCs after 48 h. Moreover the activity of etoposide after encapsulation was enhanced on H209 cells, 1050 was 100 mu M and 2.5 mu M for etoposide and etoposide LNCs respectively. Unfortunately the formulation failed to be more cytotoxic than etoposide alone on H69AR cells that are resistant to etoposide. This study showed that is was possible to obtain a new etoposide nanocarrier without the use of organic solvent, that the process is suitable for scale-up and freeze drying and finally that etoposide activity is maintained which is very promising for future treatment of SCLC.

• 出版日期2013-10-9