Are PEGylated liposomes better than conventional liposomes? A special case for vincristine

Abstract

Cancer poses a significant threat to human health worldwide, and many therapies have been used for its palliative and curative treatments. Vincristine has been extensively used in chemotherapy. However, there are two major challenges concerning its applications in various tumors: (1) Vincristine's antitumor mechanism is cell-cycle-specific, and the duration of its exposure to tumor cells can significantly affect its antitumor activity and (2) Vincristine is widely bio-distributed and can be rapidly eliminated. One solution to these challenges is the encapsulation of vincristine into liposomes. Vincristine can be loaded into conventional liposomes, but it quickly leak out owing to its high membrane permeability. Numerous approaches have been attempted to overcome this problem. Vincristine has been loaded into PEGylated liposomes to prolong circulation time and improve tumor accumulation. These liposomes indeed prolong circulation time, but the payout characteristic of vincristine is severer, resulting in a compromised outcome rather than a better efficacy compared to conventional sphingomyelin (SM)/cholesterol (Chol) liposomes. In 2012, the USA Food and Drug Administration (FDA) approved SM/Chol liposomal vincristine (Marqibo Õ ) for commercial use. In this review, we mainly focus on the drug's rapid leakage problem and the potentially relevant solutions that can be applied during the development of liposomal vincristine and the reason for conventional liposomal vincristine rather than PEGylated liposomes has access to the market.

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

“…However, the most well-known mechanism of vincristine antitumor activity involves interaction with tubulin, the basic constituent of mitotic spindle microtubules, inhibiting its polymerization and resulting in the suppression of mitosis. Therefore, it disrupts the assembly of the mitotic spindle, which in turn leads to the demise of actively-dividing cells [ 33 ]. Some authors report that at the lowest effective concentration, the anti-proliferative effect is due to a subtly change in the addition and loss of tubulins at the mitotic spindle microtubule and thus stabilizes the mitotic spindle assembly and disassembly processes that lead to metaphase arrest [ 30 ].…”

Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor in vitro and in vivo

“…Enhanced permeation and retention effect (EPR effects) and long-circulation time resulting from surface-grafted flexible and hydrophilic PEG chains enhance the accumulation of drug payloads at the site of tumor (Klibanov et al, 1990, Gref et al, 2000, Maeda et al, 2000, Iyer et al, 2006, Greish, 2007, Wang et al, 2016. Meanwhile, the exposed ligands coupled to the terminal end of PEG chains induce receptor-mediated internalization and increase affinity between liposome and cell.…”

Preparation, characterization, and efficacy of thermosensitive liposomes containing paclitaxel

“…Recently, kinds of drug delivery systems including liposomes have been studied (Wang et al, 2015). According to the physicochemical characteristics of the phospholipid membrane, liposome is a most hopeful nano-carrier with the opportunity to offer targeting therapy, thus increases the quality of cancer patient care (Ono et al, 2002;Morimoto et al, 2007;Asai et al, 2008;Abu Lila et al, 2009).…”