Host-guest complexation of cyclophosphamide by carboxylatopillar[6]arene for increasing stability and enhancing its curative effect on breast carcinoma

Abstract

Advanced chemotherapy strategies are in urgent demand for improving antitumor efficacy on breast carcinoma. Herein, a drug delivery system comprised of host-guest complex between carboxylated pillar[6]arene (CP6A) and cyclophosphamide (CTX) has been designed with view to overcoming several drawbacks associated with this antitumor agent. NMR and fluorescence titration served to confirm the complexation of CTX/CP6A. Baring CP6A did not affect cell viability as inferred from comparison studies carried out in human normal mammary epithelial cells and breast adenocarcinoma cells. Stability experiment proved that complexation of CTX by CP6A could increase the inherent stability of CTX in phosphate buffer (pH = 7.4) at 37 °C in a statistically significant way. In vivo research confirmed that CTX/CP6A was not only able to promote antitumor efficacy but also reduce CTX-related systemic toxicity on breast adenocarcinoma cells derived subcutaneous tumor xenograft mouse models. This drug delivery system could also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for more patients.

Keywords: Antitumor efficacy; Carboxylated pillar[6]arene; Cyclophosphamide; Drug delivery system; Host-guest complex; Stability.