Phytochemical delivery through nanocarriers: a review

Highlights

• Phytochemicals are secondary metabolites of plants which find application in human disease therapy.

• Stability and degradation of phytochemicals in the GI tract is a challenge which can be overcome by nano-conjugation.

• Various types of organic and inorganic nanocarriers are employed for nanoformulations.

• Biomedical applications of phytochemical nanoformulations include use as nanomedicine, antimicrobials and diagnostic agents.

Abstract

In recent times, phytochemicals encapsulated or conjugated with nanocarriers for delivery to the specific sites have gained considerable research interest. Phytochemicals are mostly plant secondary metabolites which reported to be beneficial for human health and in disease theraphy. However, these compound are large size and polar nature of these compounds, make it difficult to cross the blood-brain barrier (BBB), endothelial lining of blood vessels, gastrointestinal tract and mucosa. Moreover, they are enzymatically degraded in the gastrointestinal tract. Therefore, encapsulation or conjugation of these compounds with nanocrriers could be an alternate way to enhance their bioefficacy by influencing their gastrointestinal stability, rate of absorption and dispersion. This review presents an overview of nanocarriers alternatives which improves therapeutic value and avoid toxicity, by releasing bioactive compounds specifically at target tissues with enhanced stability and bioavailability. Future investigations may emphasize on deciphering the structural changes in nanocarriers during digestion and absorption, the difference between in-vitro and in-vivo digestion simulations, and impact of nanocarriers on the metabolism of phytochemicals.

Introduction

Phytochemicals or phytonutrients are mostly secondary metabolites of plants with a wide range of chemical structures, such as alkaloids, saponins, indoles, phytosterols, phenolic acids, isothiocyanates and phytoprostanes/furanes [[1], [2], [3]]. These metabolites are not essential for growth and development of the plant, but they are found to be beneficial for human health and disease control [[4], [5], [6]]. Phytochemicals either in their native form or their metabolites, exert beneficial effects to our health through mechanisms involving direct scavenging of free radicals, metal chelation, inhibition of the assembly of microtubules and microfilaments as well as protease inhibition [[7], [8], [9], [10]]. An important factor to assess from the metabolization point of view is the pathway after oral intake, where these phytochemicals are recognized and processed as xenobiotics by the body. The phytochemicals would go through digestion and degradation along the mouth, stomach, small and large intestines followed by absorption from the digestive tract into the blood or lymph circulation and further distribution via diffusion or transportation to body circulation, then metabolism in body tissues by biochemical conversion or degradation, and final excretion via renal, biliary, or pulmonary pathways [7,10,11]. Additionally, the maximum bioaccessibility and bioavailability of the phytochemicals result in the actual capacity to exert biological effects in vivo which is termed as bioefficacy. The bioactivity of the nutrients and non-nutrients is monitored by short-term changes in the expression of biomarkers in plasma lipid, plasma glucose, blood pressure, plasma antioxidant activity and liver function [[12], [13], [14], [15], [16]]. The dispersion and absorption of phytochemicals in the small intestine is dependent on the chemical nature and polarity of the phytochemicals. After absorption, small intestinal cells are responsible for the cellular uptake and efflux pumping while the transformation of these compounds occurs in the hepatic cells from inactive precursors to the active form which is important for the bioaccessibility of the phytochemicals [10,17]. The microbiota of the large intestine metabolize the remaining unabsorbed phytochemicals from the small intestine and thus affect the bioefficacy [10].

Thus, nanoencapsulation technology could be an alternative for the delivery of bioactive compounds in cells and tissues to prevent the harmful effect of metabolization of these compounds at operative concentrations. The nanoparticles used as carrier are designed to deliver the phytochemicals to the target site with enhanced bioefficacy. As nanoparticles comprise materials designed at the atomic or molecular level, they are usually small sized nanostructure. Hence, they can move more freely in the human body as compared to bigger materials [18,19]. Nanoparticles used as nanocarriers are basically of two types inorganic and organic. Some of the most commonly used inorganic nanocarriers include Super Paramagnetic Iron-Oxide Nanoparticles (SPIONs), Mesoporous Silica Nanoparticles and Gold/Silver nanoparticles [20]. The use of inorganic nanoparticles is very limited in drug delivery owing to their poor drug loading efficiency, high peripheral toxicity and health risks. The organic based nanocarriers are basically composed of lipids such as micelles, liposomes, niosomes, bilosomes, solid lipid nanoparticles (SLN) and archaeosomes. Lipid-based drug delivery systems are used to deliver hydrophobic drugs in the body. Encapsulation material protects the drug from degradation and avoids peripheral organ toxicity. It increases the therapeutic index of the drug, provides stability, ease of permeability and site-specific active targeting. However, inadequate knowledge about nanostructures toxicity is a major worry and need further research to improve the efficacy with higher safety to enable safer practical implementation. Therefore, cautiously designing these nanoparticles could be helpful in tackling the problems associated with their use.

Nanotechnology plays an important role in drug formation and its controlled delivery to the target site along with a controlled release [[21], [22], [23]]. Thus, this technology provides numerous plausible benefits in treating chronic human diseases by site-specific, and target-oriented delivery of medicines. Considering all the facts, this review aims to report different nanocarrier used for the conjugation of phytochemicals to enhance their stability and their significant applications as therapeutic agents.