From Nutrient to Nanocarrier: The Multifaceted Role of Vitamin B12 in Drug Delivery
Abstract
1. Introduction
2. B12 Biochemistry
2.1. Vitamin B12 Trafficking: From the Gastro-Intestinal Tract to the Blood
2.2. Vitamin B12 Trafficking: From the Blood to the Cells
2.3. Vitamin B12 Biochemistry
2.3.1. B12 as a Cofactor of Methionine Synthase
2.3.2. B12 as a Cofactor of Methylmalonyl-CoA Mutase
2.4. Non-Enzymatic Functions of B12
3. B12 Deficiency
3.1. B12 Deficiency Causes
3.2. B12 Associated Conditions
4. B12 Deficiency Treatments
4.1. Traditional Formulations
4.1.1. Use of Colloidal Systems for Delivering B12
4.1.2. Colloidal Systems Designed for B12 Delivery in the Nervous System
4.1.3. Colloidal Systems Designed to Deliver B12 for Other Conditions
5. B12 to Improve Drug Delivery in Pathological Conditions: Focus on Cancer and Other Diseases
5.1. B12-Targeted Nanoparticles for Cancer
5.2. B12—Drug Conjugates
5.3. B12 for Cancer Imaging
5.4. B12 as Anticancer Adjunctive Therapy
5.5. B12 Formulation to Improve Enteral Delivery of Antibiotics
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
HC | Haptocorrin |
TC | Transcobalamin |
Cbl | Cobalamin |
methylTHF | Methyltetrahydrofolate |
THF | Tetrahydrofolate |
MeCbl | Methylcobalamin |
AdoCbl | Adenosylcobalamin |
Hcy | Homocysteine |
SAM | S-adenosylmethionine |
SAH | S-adenosylhomocysteine |
MS | Methionine syntase |
MMUT | Mitochondrial methylmalonyl-CoA mutase |
CD320 | Receptor of transcobalamin complex with B12 |
MMA | Methylmalonic acid |
TCA cycle | Tricarboxylic acid cycle |
AhR | Aryl hydrocarbon receptor |
HPLC | High-performance liquid chromatography |
CT | Colistin |
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Cause | Mechanism | Diagnosis |
---|---|---|
Intrinsic factor deficiency | Pathogenic mutations in CBLGIF | No AIG, family context Gene sequencing |
Imerslund–Gräsbeck disease | Pathogenic mutations in CUBN and/or AMN | No AIG, family context Gene sequencing |
Biermer–Addison’s disease | AIG with impaired IF and gastric acid secretion | Endoscopy with fundic and antral biopsies IF and parietal cell autoimmunity |
Non–Biermer–Addison’s gastritis | Impaired gastric acid secretion Malabsorption of protein bound VB12 | No AIG |
Bariatric surgery and gastrectomies | Impaired IF and gastric acid secretion Bacterial overgrowth | |
Pancreatic insufficiency | Impaired degradation of HC | Pancreas imaging, lipasemia, steatorrhea |
Obstructive Jaundice | Impaired VB12 binding to IF and uptake | Imaging and biology |
Tropical sprue and celiac disease | Villous atrophy with impaired VB12-IF uptake | Anti-tranglutaminase auto-immunity |
Blind loop syndrome | Bacterial overgrowth | Breath test |
Parasitic infestations | Villous atrophy and VB12 consumption | Stool analyses |
Zollinger–Ellison syndrome | Acid intestinal pH and Impaired VB12-IF uptake | Imaging and gastrinemia |
Inflammatory bowel diseases | Parietal injury with impaired IF-B12 uptake | Endoscopy, imaging |
Chronic radiation enteritis of the distal ileum | Parietal injury with impaired IF-B12 uptake | Imaging |
Iatrogenic effects of drugs | Impaired IF-B12 uptake |
Defect in Protein | Protein Function | Phenotype |
---|---|---|
cblA (MMAA) | Loading of AdoCbl in MMUT and ejection of oxidized Cbl from MMUT | Methylmalonic acidemia, acidotic crises |
CblB(MMAB) | Chaperone for MMAA and MMUT | Similar to CblA but more severe |
CblC (MMACHC) | Decyanation, dealkylation of Cbl | Homocystinuria and methylmalonic acidemia, hematological, neurological and ophthalmic abnormalities |
CblD (MMADHC) | Adapter for MMACHC for transfer of Cbl to MS or MMAA | Isolated methylmalonic acidemia or homocystinuria, or combined methylmalonic acidemia and homocystinuria |
CblE (methionine synthase reductase) | Reduction in oxidized Cbl in MS | Similar to CblG |
cblF (LMBD1) | Escort of ABCD4 to lysosomes with endocytosed VB12-TC | Mild methylmalonic acidemia and homocystinuria, developmental delay |
CblG (MS) | Methylation of homocysteine to form methionine using MeCbl as the cofactor | Highly variable |
CblJ (ABCD4) | Transport of free Cbl from lysosomes to the cytosol | Feeding difficulties, macrocytic anemia, and congenital heart defects |
CblX (HCFC1) | Transcription coregulator HCFC1 controlling expression of MMACHC | Similar to CblC, milder metabolic representation but more severe developmental delay, choreoathetosis, and intractable epilepsy |
mut | L-methylmalonyl-CoA conversion | Isolated methylmalonic acidemia |
Formulation | Application | Particle Size, nm | Advantages | Reference |
---|---|---|---|---|
Nanoemulsion | Food enrichment with B12 | 329 ± 13 | Simple, low-energy fabrication process | [82] |
Nanoparticles | B12 delivery to bone marrow and nerve cells | 207 ± 100 | Stable aqueous dispersion, which does not require lyophiliation | [85] |
Food enrichment with B12 | ~170 | Co-encapsulation of B12 and B6 | [86] | |
Food enrichment with B12 | 260–1400 | Co-encapsulation of B12 and D3 | [87] | |
Microcapsules | Food and nutraceutical applications | ~10,000–15,000 | Fabrication of microcapsules with specific morphology and controlled release | [88] |
Liposomes | Cosmetics, food, and pharmaceutical applications | ~30–100 | N/A | [89] |
Alzheimer’s disease therapy | <200 | Improved blood–brain barrier permeation | [100] | |
Niosomes | Cosmetics, food, and pharmaceutical applications | 57 ± 18 | Lower cost and easier functionalization compared to liposomes | [89] |
Inorganic nanoparticles | Arthritis treatment | 420–640 | High loading capacity | [104] |
Arthritis treatment | ~310 | High loading capacity | [104] |
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Kuldyushev, N.A.; Simonenko, S.Y.; Goreninskii, S.I.; Pallaeva, T.N.; Zamyatnin, A.A., Jr.; Parodi, A. From Nutrient to Nanocarrier: The Multifaceted Role of Vitamin B12 in Drug Delivery. Int. J. Mol. Sci. 2025, 26, 5119. https://doi.org/10.3390/ijms26115119
Kuldyushev NA, Simonenko SY, Goreninskii SI, Pallaeva TN, Zamyatnin AA Jr., Parodi A. From Nutrient to Nanocarrier: The Multifaceted Role of Vitamin B12 in Drug Delivery. International Journal of Molecular Sciences. 2025; 26(11):5119. https://doi.org/10.3390/ijms26115119
Chicago/Turabian StyleKuldyushev, Nikita A., Sergey Y. Simonenko, Semen I. Goreninskii, Tatiana N. Pallaeva, Andrey A. Zamyatnin, Jr., and Alessandro Parodi. 2025. "From Nutrient to Nanocarrier: The Multifaceted Role of Vitamin B12 in Drug Delivery" International Journal of Molecular Sciences 26, no. 11: 5119. https://doi.org/10.3390/ijms26115119
APA StyleKuldyushev, N. A., Simonenko, S. Y., Goreninskii, S. I., Pallaeva, T. N., Zamyatnin, A. A., Jr., & Parodi, A. (2025). From Nutrient to Nanocarrier: The Multifaceted Role of Vitamin B12 in Drug Delivery. International Journal of Molecular Sciences, 26(11), 5119. https://doi.org/10.3390/ijms26115119