Improving In Vivo Efficacy of Bioactive Molecules: An Overview of Potentially Antitumor Phytochemicals and Currently Available Lipid-Based Delivery Systems

Lamia Mouhid, Marta Corzo-Martínez, Carlos Torres, Luis Vázquez, Guillermo Reglero, Tiziana Fornari, Ana Ramírez de Molina, Lamia Mouhid, Marta Corzo-Martínez, Carlos Torres, Luis Vázquez, Guillermo Reglero, Tiziana Fornari, Ana Ramírez de Molina

Abstract

Cancer is among the leading causes of morbidity and mortality worldwide. Many of the chemotherapeutic agents used in cancer treatment exhibit cell toxicity and display teratogenic effect on nontumor cells. Therefore, the search for alternative compounds which are effective against tumor cells but reduce toxicity against nontumor ones is of great importance in the progress or development of cancer treatments. In this sense, scientific knowledge about relevant aspects of nutrition intimately involved in the development and progression of cancer progresses rapidly. Phytochemicals, considered as bioactive ingredients present in plant products, have shown promising effects as potential therapeutic/preventive agents on cancer in several in vitro and in vivo assays. However, despite their bioactive properties, phytochemicals are still not commonly used in clinical practice due to several reasons, mainly attributed to their poor bioavailability. In this sense, new formulation strategies are proposed as carriers to improve their bioefficacy, highlighting the use of lipid-based delivery systems. Here, we review the potential antitumoral activity of the bioactive compounds derived from plants and the current studies carried out in animal and human models. Furthermore, their association with lipids as a formulation strategy to enhance their efficacy in vivo is also reported. The development of high effective bioactive supplements for cancer treatment based on the improvement of their bioavailability goes through this association.

Figures

Figure 1
Figure 1
Determinant factors of the oral bioavailability of bioactive compounds, including phytochemicals.
Figure 2
Figure 2
Types of (nano)carriers used to increase bioefficacy of phytochemicals. Those developed for oral administration of active compounds are in italic characters.
Figure 3
Figure 3
Mode of action of lipid-based delivery systems designed for the efficient oral administration of phytochemicals. (A) Allowing paracellular transport by opening tight junction; (B) facilitating transcellular absorption due to increased membrane fluidity; (C) promotion of phagocytosis via specialized microfold cells (M cells) of Peyer's patches; (D) increased intracellular concentration and residence time by surfactants due to inhibition of P-gp and/or CYP450; (E) lipid stimulation of lipoprotein/chylomicron production.
Figure 4
Figure 4
Schematic representation of the different types of liposomal drug delivery systems: (A) conventional liposome; (B) PEGylated liposome; (C) ligand-targeted liposome; (D) theranostic liposome (reprinted from Frontiers in Pharmacology, 6, article 286, 1–12. Advances and Challenges of Liposome Assisted Drug Delivery, by Sercombe et al. [87], with permission from the authors).
Figure 5
Figure 5
Structure of solid lipid nanoparticles (SLNs) versus nanostructured lipid carriers (NLCs).

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