The Precision Nutraceutical Delivery Continuum: A Critical Review of Nanoencapsulation Strategies Bridging Pharmaceutical Engineering and Personalized Nutritional Therapy

Abstract

Most bioactive nutraceuticals and many oral pharmaceuticals share a common translational bottleneck: poor aqueous solubility, gastrointestinal instability, and low systemic bioavailability that blunt their clinical and nutritional benefit. Nanoencapsulation — the entrapment of a bioactive within a nanoscale lipid, polymeric, or hybrid carrier — has become the dominant engineering strategy to overcome this bottleneck, and the literature on individual carrier types (liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric and chitosan-based nanoparticles, nanoemulsions) or individual bioactives (curcumin, resveratrol, quercetin, omega-3 polyunsaturated fatty acids, probiotics and postbiotics, micronutrients) has grown rapidly and largely in isolation. This review synthesises that fragmented evidence base into a single analytical frame. First, it summarises carrier chemistry, fabrication technologies (spray drying, electrospinning/ electrospraying, coacervation, ionic gelation, nanoprecipitation), and encapsulation-efficiency and bioavailability outcomes across five major bioactive classes, drawing on 50 verifiable primary and secondary sources published mainly between 2020 and 2026. Second, and as its principal novelty, the review proposes the Precision Nutraceutical Delivery Continuum (PNDC), a conceptual framework that cross-maps four generations of nanocarrier sophistication (conventional carriers, first-generation lipid/polymeric systems, stimuli-responsive smart carriers, and microbiome-/genotype-adaptive carriers) against four layers of inter-individual physiological variability (gastric pH-motility phenotype, gut-microbiome enterotype, pharmacogenomic and nutrigenomic polymorphism, and disease-specific metabolic state). The PNDC is offered as a hypothesis-generating design heuristic — not an empirically validated algorithm — intended to guide the next generation of "nanocarrier-phenotype matching" studies at the interface of pharmacy and nutrition science. Third, the review evaluates the regulatory and safety landscape governing nano-enabled nutraceuticals under the European Food Safety Authority, the United States Food and Drug Administration, and Indonesia's Food and Drug Authority (BPOM), including halal-assurance considerations relevant to Southeast Asian markets. We conclude that nanoencapsulation has matured from a bioavailability-enhancement tool into a platform technology with the potential to individualise nutritional therapeutics, but that its clinical translation is constrained by heterogeneous in vitro-in vivo correlation, insufficient long-term nanotoxicological data, and regulatory frameworks that have not yet caught up with stimuli-responsive and precision-oriented carrier designs.