Targeted nanoliposomal nutrient delivery for human health

Table 1 Comparative analysis of conventional oral supplements and nanoliposomal delivery systems

Aspect	Conventional oral supplements	Nanoliposomal delivery systems
Gastric stability	Low: Vulnerable to acidic pH and enzymatic degradation	High: Encapsulation within phospholipid bilayers confers protection against gastric acid and enzymatic hydrolysis
Intestinal absorption	Limited: Constrained by poor solubility and epithelial permeability	Enhanced: Improved solubility and interaction with enterocyte uptake mechanisms (e.g., endocytosis)
First-pass metabolism	Pronounced: Hepatic metabolism via portal vein reduces bioactivity	Attenuated: Lymphatic transport via chylomicrons partially circumvents hepatic first-pass metabolism
Systemic distribution	Non-specific: Diffuse dilution across systemic tissues	Targeted: Surface ligands enable receptor-mediated delivery to specific tissues
Bioavailability	Suboptimal: High doses required to achieve therapeutic levels	Superior: Increased efficiency permits lower effective doses
Therapeutic index	Variable: Elevated doses may precipitate gastrointestinal adverse effects	Optimized: Targeted delivery enhances efficacy while minimizing off-target toxicity

Conventional oral supplement absorption: Depicts the degradation of an ingested supplement in the acidic stomach environment (pH approximately 1.0-2.0), followed by enzymatic breakdown in the intestinal lumen. A minor fraction traverses the intestinal epithelium into the portal circulation, undergoing substantial first-pass metabolism in the liver, resulting in diminished systemic bioavailability. Nanoliposomal nutrient delivery: Illustrates a nanoliposome-encapsulated nutrient resisting gastric degradation due to its protective lipid bilayer. Upon reaching the small intestine, the liposome is absorbed via enterocytes or lymphatic pathways (e.g., chylomicron-mediated transport), partially bypassing hepatic metabolism. Functionalized ligands on the liposome surface facilitate receptor-mediated endocytosis into target tissues, with subsequent endosomal escape mechanisms ensuring cytosolic delivery. This culminates in elevated bioavailability and concentrated nutrient deposition at intended sites.

Table 2 Examples of targeting strategies for nanoliposomal nutrient delivery

Target organ/cell	Targeting ligand on liposome	Example outcome
Intestinal M cells (Peyer’s patches)	Ulex europaeus agglutinin I (lectin) or targeting peptide for M cells	Enhanced uptake of oral liposome via Peyer’s patches, often utilized in oral vaccine delivery (concept can be extrapolated to nutrients)
Intestinal enterocytes	Folic acid (folate receptor targeting)	Increased oral absorption of hydrophilic compounds by folate receptor - mediated uptake; may similarly improve nutrient uptake
Liver (hepatocytes)	Galactose or N-acetyl galactosamine (asialoglycoprotein receptor ligand)	Specific delivery to hepatocytes (e.g., for vitamin A or D) via the asialoglycoprotein receptor, which binds galactose-terminated ligands
Liver (stellate cells)	Mannose-6-phosphate or vitamin A (retinol)	Hepatic stellate cells naturally store vitamin A; thus, vitamin A-decorated liposomes can deliver anti-fibrotic nutrients to stellate cells in liver fibrosis
Brain (neurons or blood-brain barrier)	Transferrin or anti-transferrin receptor antibody	Enables liposomes to cross the blood-brain barrier via transferrin receptor - mediated transcytosis, facilitating delivery of neuroprotective nutrients to the central nervous system
Heart (cardiomyocytes)	Peptide targeting mitochondria or surface markers (e.g., for myosin or angiotensin II type 1 receptor)	Experimental strategy to deliver coenzyme Q10 or antioxidants to heart muscle. In certain models, angiotensin-targeted nanoparticles accumulate preferentially in cardiac tissue
Kidney (glomerular mesangial cells)	Anti-Thy1.1 antibody (in rats) or anti-integrin α8 antibody	Achieves a marked increase (e.g., approximately 6-fold) in liposome accumulation within renal glomeruli, allowing targeted delivery of antioxidants or other agents to mesangial cells, potentially benefiting nephritis therapy
Kidney (proximal tubule)	Lysozyme or small peptide (binds megalin receptor)	Enhances uptake into proximal tubule cells; may deliver vitamin E or carotenoids to mitigate oxidative damage in chronic kidney disease
Immune cells (macrophages)	Mannose (mannose receptor targeting)	Facilitates uptake by macrophages (e.g., in spleen or liver). Could be used to deliver anti-inflammatory vitamins (e.g., vitamin D) to macrophages in immune-related organs
Tumor (for cancer prevention)	Arginine-glycine-aspartic acid peptide (targets integrin on angiogenic endothelium)	Allows liposomes to accumulate in tumor neo vasculature, potentially delivering high doses of selenium or other antitumor nutrients in a localized manner (extrapolated from drug-targeting approaches)

The above examples include some drug delivery contexts extended to nutrients for illustrative purposes. Actual nutraceutical targeting is an emerging field and not all strategies have been applied to nutrients yet. However, the same principles of ligand-receptor targeting apply to any payload, whether drug or nutrient.