Abstract
Simple SummaryAlkaloids are natural products that possess numerous pharmacological activities and have been exploited effectively to treat cancer. However, the clinically approved anticancer alkaloids are generally limited by serious side effects due to their lack of specificity to cancer cells, indiscriminate tissue distribution and toxic formulation excipients. Lipid-based nanoparticles represent the most effective drug delivery system concerning clinical translation owing to their unique appealing characteristics for drug delivery. This review aims to assess the potential of different types of lipid-based nanoparticles in encapsulating anticancer alkaloids. Our review shows that alkaloids encapsulated in lipid-based nanoparticles generally displayed an enhanced efficacy and toxicity profile than unencapsulated alkaloids in various cancers. Encapsulated alkaloids also demonstrated the ability to overcome multidrug resistance in cell lines and animal models. These findings support the broad application of lipid-based nanoparticles to encapsulate anticancer alkaloids and facilitate their clinical translation.Since the commercialization of morphine in 1826, numerous alkaloids have been isolated and exploited effectively for the betterment of mankind, including cancer treatment. However, the commercialization of alkaloids as anticancer agents has generally been limited by serious side effects due to their lack of specificity to cancer cells, indiscriminate tissue distribution and toxic formulation excipients. Lipid-based nanoparticles represent the most effective drug delivery system concerning clinical translation owing to their unique, appealing characteristics for drug delivery. To the extent of our knowledge, this is the first review to compile in vitro and in vivo evidence of encapsulating anticancer alkaloids in lipid-based nanoparticles. Alkaloids encapsulated in lipid-based nanoparticles have generally displayed enhanced in vitro cytotoxicity and an improved in vivo efficacy and toxicity profile than free alkaloids in various cancers. Encapsulated alkaloids also demonstrated the ability to overcome multidrug resistance in vitro and in vivo. These findings support the broad application of lipid-based nanoparticles to encapsulate anticancer alkaloids and facilitate their clinical translation. The review then discusses several limitations of the studies analyzed, particularly the discrepancies in reporting the pharmacokinetics, biodistribution and toxicity data. Finally, we conclude with examples of clinically successful encapsulated alkaloids that have received regulatory approval and are undergoing clinical evaluation.
Highlights
Cancer ranks as the leading cause of morbidity and mortality in the world with an estimated 19.3 million new cases and 9.9 million deaths reported in 2020 [1]
This section summarizes the limitations of taxanes, vinca alkaloid and topoisomerase I inhibitor to provide an overview of the challenges faced by these approved drugs and to provide insights into the obstacles possibly holding back the successful commercialization of promising alkaloids
The approval was based on the global phase III NAPOLI-1 trial which reported that the addition of Onivyde significantly improved the median overall survival (OS) compared with 5-fluorouracil + folinic acid alone (6.1 months vs. 4.2 months) with a manageable safety profile in patients who progressed after gemcitabine-based therapy [195]
Summary
Cancer ranks as the leading cause of morbidity and mortality in the world with an estimated 19.3 million new cases and 9.9 million deaths reported in 2020 [1]. Lipid-based nanoparticles have received great attention due to their unique, appealing characteristics for drug delivery, including (1) excellent biocompatibility and biodegradability; (2) improved solubility and Cancers 2021, 13, 5346 stability of difficult-to-deliver drugs, including both hydrophobic and hydrophilic drugs; (3) enhanced therapeutic index by improving efficacy and reducing toxicity; (4) versatility which allows chemical modifications and surface coatings and (5) ability of co-deliver two different anticancer drugs to enable precise spatiotemporal multi-drug treatment [22,23,24,25] These advantages of lipid-based nanoparticles have been exploited effectively in enhancing the efficacy and reducing the toxicity of anticancer alkaloids, the most exceptional of which are Onivyde (liposomal irinotecan), Marqibo (liposomal vincristine) and Lipusu (liposomal paclitaxel), which have received regulatory approval for clinical use [26]. To the extent of our knowledge, this is the first review to compile the in vitro and in vivo evidence of encapsulating anticancer alkaloids in lipid-based nanoparticles
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