Caprylate-Conjugated Cisplatin for the Development of Novel Liposomal Formulation

Abstract

Abstract. Cisplatin, first (platinum) compound to be evolved as an anticancer agent, has found its important place in cancer chemotherapy. However, the dose-dependent toxicities of cisplatin, namely nephrotoxicity, ototoxicity, peripheral neuropathy, and gastrointestinal toxicity hinder its widespread use. Liposomes can reduce the toxicity of cisplatin and provide a better therapeutic action, but the low lipid solubility of cisplatin hinders its high entrapment in such lipid carrier. In the present investigation, positively charged reactive aquated species of cisplatin were complexed with negatively charged caprylate ligands, resulting in enhanced interaction of cisplatin with lipid bilayer of liposomes and increase in its encapsulation in liposomal carrier. Prepared cisplatin liposomes were found to have a vesicular size of 107.9±6.2 nm and zeta potential of −3.99±3.45 mV. The optimized liposomal formulation had an encapsulation efficiency of 96.03±1.24% with unprecedented drug loading (0.21 mg cisplatin/mg of lipids). The in vitro release studies exhibited a pH-dependent release of cisplatin from liposomes with highest release (67.55 ± 3.65%) at pH 5.5 indicating that a maximum release would occur inside cancer cells at endolysosomal pH. The prepared liposomes were found to be stable in the serum and showed a low hemolytic potential. In vitro cytotoxicity of cisplatin liposomes on A549 lung cancer cell line was comparable to that of cisplatin solution. The developed formulation also had a significantly higher median lethal dose (LD 50 ) of 23.79 mg/kg than that of the cisplatin solution (12 mg/kg). A promising liposomal formulation of cisplatin has been proposed that can overcome the disadvantages associated with conventional cisplatin therapy and provide a higher safety profile.

TPGS-modified liposomes for the delivery of ginsenoside compound K against non-small cell lung cancer: formulation design and its evaluation in vitro and in vivo

“…In previous reports, various drug delivery systems have been developed for enhancing the antitumour effect of the active ingredients, such as micelles, liposomes and nanoparticles . Among these delivery systems, liposome is considered to be a stronger prospective alternatives as several of these formulations have been under clinical assessment for anticancer . However, the traditional liposomes came with some serious problems, such as instability, insufficient drug loading, fast drug release and short blood circulation .…”

Current Strategies to Combat Cisplatin-Induced Ototoxicity

“…Drug delivery carriers are also suitable for use with cisplatin, including NPs, liposomes, micelles (Baba et al, 2012), and nanocapsules (Boulikas, 2009;Vhora et al, 2014). These can selectively and effectively accumulate in solid tumors, enhancing anticancer potential and reducing toxicity.…”

Recent progress in nanotechnology-based novel drug delivery systems in designing of cisplatin for cancer therapy: an overview

“…Vhora et al reported that the sterol cisplatin-based liposome demonstrated the greater half-life as a match free drug. The X-ray fluorescence spectroscopy technique was used to determine the platinum content in the formulation [85]. Another research group reported that the liposomes formulation was designed to overcome the problem regarding poor solubility of cisplatin, improvement of the therapeutic index and safety profile [86].…”