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.

Background: Dryobalanops rappa is a plant species belonging to the family of Dipterocarpaceae. Nevertheless, the active compounds present in D. rappa have never been investigated. Objective: The aim of this research is to isolate and characterize compounds from Dryobalanops rappa and to study its bioactivity against human MCF-7 breast cancer and A549 lung cancer cell lines and several bacterial strains. Methods: The isolation step was carried out using a combination of chromatographic techniques. The structure of the isolated compounds was elucidated mainly using NMR spectroscopy. The cytotoxic activity of isolated compounds was determined with MTT assay, and the antimicrobial was screened using a modified resazurin microtiter-plate assay. Results: Isolation and purification of methanolic extract of D. rappa stem bark yielded 14 known oligomeric resveratrol types of compounds (1-14). Results showed that isolated ampelopsin E (5) and vaticanol C (14) displayed moderate activity against human MCF-7 breast cancer and A549 lung cancer cell lines with IC₅₀ values 14.3 and 10.7 μg/mL, respectively. Interestingly, acetate derivative of isolated laevifonol (2) and ampelopsin F (3) was found to possess potent activities towards MCF-7 cancer cell line with IC₅₀ values 2.8 and 3.3 μg/mL, respectively, in comparison to the parental compounds that demonstrated weak activities (IC₅₀ > 50 μg/mL). For the antibacterial assay, compounds 10 and 12 showed moderate activities towards Gram-positive bacterial strains (MIC ≤ 50 μM). Conclusion: 14 known oligomeric resveratrol types of compounds have been isolated. The activity of 14 against A549 cell line, 5 against MCF-7 cell line, and 10 and 12 against Gram-positive bacterial strains were the most promising results of this study. While the strong cytotoxicity of acetate derivative (2 and 3) against MCF-7 cell line has revealed the potential of resveratrol oligomers to be used as a template for designing new anticancer drugs.