Advanced Oral Delivery Systems for Nutraceuticals

Abstract

Oral delivery is the most preferred route for nutraceuticals due to its convenience and high patient compliance. However, bioavailability is often compromised by poor solubility, instability, and first-pass metabolism in the gastrointestinal tract. This review examines current and emerging oral delivery platforms designed to overcome these barriers and enhance nutraceutical efficacy.

Traditional carriers—proteins, lipids, and carbohydrates highlighting their delivery mechanisms and limitations, are first explored. Advancements in material science have led to novel platforms such as biodegradable polymers, metal–organic frameworks (MOFs), metal–polyphenol networks (MPNs), and 3D printing technologies. Biodegradable polymers improve stability and enable controlled release of bioactives. MOFs offer high surface area and tunable porosity for encapsulating and protecting sensitive compounds. MPNs provide biocompatible, stimuli-responsive systems for targeted nutrient delivery. Meanwhile, 3D printing facilitates the fabrication of personalized delivery systems with precise control over composition and release kinetics, especially when integrated with artificial intelligence (AI) for precision nutrition.

By comparing traditional and next-generation strategies, this review outlines key design principles for optimizing oral delivery systems. The transformative potential of these innovations is underscored to improve the bioavailability and therapeutic outcomes of nutraceuticals, ultimately advancing personalized and targeted nutrition solutions.

Introduction

Nutraceuticals, a term blending “nutrition” and “pharmaceutical,” encompass food-derived products that provide health benefits beyond basic nutritional value, including the prevention and treatment of diseases.[1] They include both nutrients and bioactive compounds, both of which are integral to human health.[2] Nutrients are substances required for growth, metabolism, and other bodily functions, which are broadly classified into macronutrients—carbohydrates (sugars and dietary fibers), proteins, and fats—and micronutrients—vitamins and minerals such as sodium, potassium, iodine, iron, zinc, and calcium.[3] Macronutrients are needed in larger quantities and serve as primary energy sources and structural components of cells, while micronutrients are essential for biochemical and physiological processes in cells and tissues, albeit required in smaller amounts [4] For instance, calcium and magnesium are vital for bone health and can help prevent osteoporosis, whereas chromium plays a role in enhancing glucose tolerance.[5] Furthermore, nutraceuticals can be administeredorallyindiverseformats—suchascapsules,tablets, protein shakes, and fortified foods—to accommodate different dietary needs and preferences.

Table 1. Nutraceuticals, their Sources, and health benefits.

In addition to essential nutrients, nutraceuticals include various bioactive compounds that exert beneficial effects on human health.[6] These compounds, often derived from plant and animal sources, encompass phytochemicals[7] (such as polyphenols and flavonoids), carotenoids,[8] phytosterols, and probiotics.[9] Phytochemicals like resveratrol and epigallocate chin gallate (EGCG) have demonstrated antioxidant and anti inflammatory properties, contributing to cardiovascular health and cancer prevention.[10] Carotenoids, including 𝛽-carotene, lutein, and zeaxanthin, are associated with eye health, potentially reducing the risk of age-related macular degeneration and cataracts.[11] Probiotics—beneficial live microorganisms—enhance gut health by modulating the intestinal microbiota and improving immunefunction.[12] The sources and health benefits of nutraceuticals have been summarized in Table 1. Oral administration remains the most favorable route for delivering nutraceuticals due to its non-invasiveness, convenience, and high patient compliance.[24] However, the efficacy of orally administered nutraceuticals is often limited by several physiological and biochemical barriers within the gastrointestinal (GI) tract.[25] These challenges[24] include (1) physicochemical instability– many nutraceuticals are sensitive to the acidic environment of the stomach, enzymatic degradation, and interactions with other dietary components, leading to reduced bioactivity before absorption;[26] (2) poor solubility and permeability– a significant number of bioactive compounds have low water solubility and limited permeability across the intestinal epithelium, resulting in suboptimal absorption and therapeutic effects;[27] (3) first-pass metabolism– the hepatic first-pass effect can extensively metabolize certain compounds before they reach systemic circulation, decreasing their bioavailability and necessitating higher doses, which may increase the risk of side effects;[28] (4) gastrointestinal transit variability-variations in gastric emptying time and intestinal transit can affect the residence time ofnutraceuticals at absorption sites, leading to inconsistent plasma concentrations [29]

Figure 2. The source of polysaccharide for oral delivery platform. — **Figure 2.** The source of polysaccharide for oral delivery platform.

To overcome these obstacles, developing advanced oral delivery platforms is essential. These platforms aim to protect and stabilize active ingredients, enhancing their bioavailability and ensuring they exert their physiological or therapeutic effects effectively.[30] By stabilizing nutraceuticals, these delivery systems not only improve efficacy, but also contribute to creating affordable health solutions. This is particularly important for underserved populations in developing and underdeveloped regions, where access to effective nutraceuticals can significantly impact public health outcomes.[31] Enhancing the stability and bioavailability of nutrients and bioactive compounds through innovative delivery systems can make vital contributions to global health by increasing access to essential nutraceuticals. This review aims to summarize the current status of oral de livery platforms for nutraceuticals, discuss existing problems and challenges, and highlight recent innovations (Figure 1).

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