Design and in vitro evaluation of solid SEDDS for breast cancer therapy

Abstract

Lipid-based drug delivery systems have been used as a useful tool for the formulation of hydrophobic drugs giving us the opportunity to enhance permeation from biological membranes, protecting active ingredients from harsh in vivo environment, thus enhancing the bioavailability. Self-emulsifying drug delivery systems could be classified as one of lipid-based formulation strategies and their ability to provide a key solution to the solubility problems faced with most of the anticancer drugs, and ease of production, make them a popular choice. The use of SEDDS for the formulation of peptide-protein drugs to overcome in vivo stability problems comes from the protective effect of these formulations over enzymes in gastrointestinal tract and give us the opportunity to design an oral application platform. In this study, we used an anticancer peptide, LyP-1, with lymphatic targeting properties as model molecule for the solidification of SEDDS preconcentrates. As lyophilization and spray-drying techniques were used for the production of solid SEDDS, characterization studies were conducted to optimize the formulation parameters and evaluate the permeation enhancing effect of these novel formulations. The cell culture studies were utilized for the assessment of biocompatibility using Caco-2 cell line and anticancer properties were evaluated using MDA-MB-231 cell line. Solid SEDDS with droplet size under 250 nm were obtained with lyophilization and spray-drying method using mannitol and magnesium aluminometasilicate as adsorbents. The anticancer activity of solid SEDDS formulations containing LyP-1 peptide prepared with two different solidification method was shown using MDA-MB-231 cell line. The permeability enhancing effect of excipients used in SEDDS were observed in Caco-2 cell monolayer indicating the absorption enhancing potential of prepared formulations, especially for spray-dried powders.