Original ArticleNatural lipids enriched self-nano-emulsifying systems for effective co-delivery of tamoxifen and naringenin: Systematic approach for improved breast cancer therapeutics
Graphical Abstract
The oral administration of TMX-NG-SNEDDS leads to nano micelles formation in situ to owing to presence of the smart ingredients, which leads its lymphatic uptake, and multiple fold enhanced bioavailability revealed through pharmacokinetics parameters; the results corroborated the same using cell cytotoxicity on MCF-7 cells and flow cytometry of the samples with more than 84% apoptosis. The natural ingredients however, marked safe and effective role of the optimized formulation as evident from caco-2 cell line studies and Kaplan survival curve, % tumor burden after treatment period.
Section snippets
Materials
TMX was gifted by M/s Cipla Ltd., India, while NG was purchased from M/s Sigma Aldrich, India. Labrasol, Labrafil 1944 CS, Transcutol P, Acconon C 6, Capryol-90, were obtained ex-gratis from M/s Gattefosse, France. Various PUFA-rich oils viz. peanut oil, corn oil, sesame oil, soyabean oil, sunflower oil, and surfactants like PEG 400, Tween 80, Caproyl 90, Acconon CC-6, Acrysol EC-35 were procured from M/s S.D. Fine Chemicals, Mumbai, India and cosolvents like Transcutol P, Transcutol HP were
Formulation development and optimization
The formulations were prepared using apt combination of selected excipients (i.e., corn oil-lipid, labrasol-solvent, andtranscutol-P, i.e., co-solvent. And QbD-based D-optimal mixture design had provided the best optimal solution (supplementary data).
Characterization of the SNEDDS
The globule size diameter of the formulation was found to be ranging between 52 and 73 nm, thus confirming the nano-structured nature of the emulsion globules obtained after dilution in presence of SGF.18, 19, 20 The TEM images of the TMX-NG–SNEDDS
Discussion
The study is about the self-nano-emulsifying drug delivery system employing natural lipids and biocompatible, safe excipients, with enhanced bioavailability and bioflavonoid for synergistic anticancer potentials, with respect to TMX.28 The characterization revealed that the SNEDDS exhibited faster micelles forming efficiency, the drug release profiles showed immediate release exhibiting complete drug in <30 min.18 The in vitro cellular cytotoxicity studies on Caco-2 and MCF-7 cells showed
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Conflict(s) of interest: The authors declare no conflict(s) of interest.