Preparation and <i>in Vivo</i> Evaluation of Liposomal Everolimus for Lung Carcinoma and Thyroid Carcinoma

Abstract

Everolimus has demonstrated antitumor efficacy for various cancers as a result of its inhibition of the mammalian target of rapamycin (mTOR) signaling cascade, which activates cell growth and cell proliferation. However, the low water solubility and low bioavailability of everolimus have prevented its clinical development as an anticancer drug. Therefore, to address the unsuitable characteristic of everolimus, we attempted to prepare liposomal everolimus as a viable drug delivery system, and then evaluated the anticancer efficacy of this system against a medullary thyroid carcinoma cell line (TT cells), a breast cancer cell line (MCF-7 cells) and a small lung carcinoma cell line (NCI-H446 cells). The particle size and entrapment efficacy of liposomal everolimus was ca. 80 nm and more than 90%, respectively. Liposomal everolimus showed higher cytotoxicity against NCI-H446 cells compared with TT cells. Against NCI-H446 tumors, significant suppression of the tumor volume was observed in liposomal everolimus-treated mice by intravenous injection, compared with free everolimus-treated mice by intraperitoneal injection, at a dose of 5 mg/kg without body weight loss. This study showed that liposomal everolimus could be a powerful formulation with anticancer efficacy for some cancers.

Glycolysis in Panc-1 human pancreatic cancer cells is inhibited by everolimus

“…Everolimus, as a rapamycin analog, is an inhibitor of mTORC1 (16). Several studies have demonstrated that everolimus inhibits the growth of several cancer cell lines in vitro and inhibits tumor growth in animal models (12,17). However, the detailed mechanism of everolimus in the treatment of pancreatic cancer remains unclear.…”

A three-drug nanoscale drug delivery system designed for preferential lymphatic uptake for the treatment of metastatic melanoma

“…DTX acts by stabilizing the microtubules, EVR and LY act on mammalian target of rapamycin, mTORC1 and mTORC2, respectively. [26][27][28] Together, EVR and LY, can completely inhibit the mTOR pathway while LY is also capable of inhibiting the Phosphoinositide 3-Kinase (PI3K) pathway. [27,28] However, IV or SC administration of these molecules individually or together will lead to systemic absorption with little accumulation in the lymphatic system.…”

“…[26][27][28] Together, EVR and LY, can completely inhibit the mTOR pathway while LY is also capable of inhibiting the Phosphoinositide 3-Kinase (PI3K) pathway. [27,28] However, IV or SC administration of these molecules individually or together will lead to systemic absorption with little accumulation in the lymphatic system. Nanoparticles (NP), prepared with amphiphilic block copolymers, are drug delivery systems that can be modified to target the lymphatic system.…”

Nanopreparations to overcome multidrug resistance in cancer

“…It was observed that the non-PEGylated liposome-drug formulation was more active in terms of anti-proliferative efficacy while the PEGylated liposome-drug was more stable [213]. Iwase et al ., prepared liposomal everolimus (rapamycin analog) for in vivo targeting and improved therapeutic efficacy towards lung and thyroid cancers [214]. HIF-1 activity can also be influenced by Hsp90 inhibition [206, 211].…”