Vincristine-based nanoformulations: a preclinical and clinical studies overview

Abstract

Vincristine (VCR) is a chemotherapeutic agent obtained from natural alkaloid plant source Catharanthus roseus. VCR has been significantly useful in treatments of lung cancer, lymphocyte-based leukaemia, glioblastomas and acute myeloid leukaemia. VCR attaches to tubulin fibrils and prevents filament polymerization that permanently led to mitosis inhibition in cancer cells. Clinically, VCR is administered to patients in multidrug combination to reduce adverse drug effects and potential blockage of bone marrow inhibition due to prescribed monotherapy. However, VCR possesses low cancer tissue affinity and at higher dose often led to irreversible neurotoxicity. Conventional VCR injectables are successfully used in clinics, but lack of controlled release, non-specific biodistribution and consequent off-target side effects are still major challenges. Currently, nanotechnological drug delivery systems are being explored for improvement of VCR pharmacokinetic profile and tumour-specific targeting. Various nanomedicine formulations such as liposomes, lipid nanoparticles, and polymeric nanocarriers of VCR have been studied under various in vitro and in vivo models. In this review, we have summarised the chemotherapeutic role of VCR, evaluated the mechanism of action, pharmacokinetics and challenges associated with VCR delivery. Moreover, application of VCR in nanomedicine and effect on anticancer efficacy in preclinical and clinical setting are also being discussed. Graphical Abstract

Alendronate-Grafted Nanoemulsions for Bone-Targeted Vincristine Delivery: Preliminary Studies on Cell and Animal Models

“…Indeed, nanocarriers can generally either be loaded or grafted with low amounts of selected compounds, meaning that only potent drugs can be successfully delivered using nanocarriers. While vincristine is a microtubule inhibitor, which can act on several tumour-growth mechanisms (i.e., proliferation, migration) at low doses [4], only nitrogen-containing bisphosphonates exert any antitumour activity [17]. ALD, which is a nitrogen-containing bisphosphonate, was selected because it can be chemically grafted onto nanoemulsion droplets [14].…”

“…Vincristine, a microtubule polymerisation inhibitor, is a broad-spectrum cytotoxic agent that is widely employed in oncology [4]. It has also been reported to act as an efficacious treatment against skeletal metastases from medulloblastoma [5].…”

“…Clinically, it is administered in combination with other drugs to reduce adverse drug effects, especially bone marrow inhibition, that may be caused by mono-therapy. However, its low cancer affinity means that off-target biodistribution can lead to considerable side effects, including irreversible neurotoxicity, which are currently a relevant limitation to its usage [4].…”

Can Some Anticancer Drugs Be Repurposed to Treat Amyotrophic Lateral Sclerosis? A Brief Narrative Review

“…Binding to the β-tubulin of axon microtubules leads to peripheral neuropathy, representing the major side effect of the long-term administration of vincristine [86]. However, at lower doses or in the presence of a higher clearance rate, vincristine binds tubulin in a reversible manner; its antitumour efficacy as well as its neurotoxicity are thus strictly dependent on the dose and the length of exposure [87].…”

Insights into Metabolites Profiling and Pharmacological Investigation of Aconitum heterophyllum wall ex. Royle Stem through Experimental and Bioinformatics Techniques

“…About 67% effective cancer drugs are derived from NPs such as vincristine and vinblastine from various plant species. 5,64,65 The plants of the genus aconitum chemically include steroids, glycosides, alkaloids, and flavonoids. Diterpenoid alkaloids are considered toxic as well as the main efficient anticancer components of these plants.…”