In Vivo Antitumor Activity of Neratinib and Paclitaxel Loaded Cubosomes in an MCF-7 Breast Cancer Xenograft Model

Abstract

Background: Cubosomes are bicontinuous lipid nanocarriers capable of incorporating poorly water-soluble drugs and modifying their release. This study investigated the antitumor performance of neratinib-loaded cubosomes administered alone or together with separately prepared paclitaxel-loaded cubosomes in an MCF-7 breast cancer xenograft model. Methods: Fifteen female BALB/c nude mice bearing MCF-7 xenografts were allocated to five groups (n=3): saline control, neratinib suspension (10 mg/kg), paclitaxel suspension (5 mg/kg), neratinib loaded cubosomes (10 mg/kg), and co-administration of separately formulated neratinib and paclitaxel-loaded cubosomes (10 and 5 mg/kg). Five intraperitoneal administrations were given at three-day intervals during a 14-day observation period. Tumor volume and body weight were assessed serially. Results: Day-14 mean tumor volumes were 1021.79 ± 49.54, 559.07 ± 32.24, 462.57 ± 27.68, 275.59 ± 20.48 and 127.20 ± 29.02 mm³, respectively. Relative to the control, end-point mean tumor volumes were lower by 45.29%, 54.73%, 73.03% and 87.55% in the treated groups. Body-weight changes were −2.58%, −3.26%, −8.18%, +0.83% and −0.40%, respectively. Conclusion: The co-administered cubosomal formulations were associated with the lowest mean end-point tumor volume. These findings support further investigation of combined cubosomal delivery; the design does not establish pharmacological synergy or systemic safety.

Keywords: cubosomes; neratinib; paclitaxel; breast cancer; MCF-7 xenograft; lipid nanoparticles; antitumor activity