Generation of nanobodies targeting the human, transcobalamin-mediated vitamin B12 uptake route (original) (raw)
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Nanomaterials
Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients’ lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption. Furthermore, the high-dose injection of VitB12 does not ensure a constant dosage, while the oral route allows only 1.2% of the vitamin to be absorbed in human beings. Nanocarriers are promising nanotechnology that can enable therapies to be improved, reducing side effects. Today, nanocarrier strategies applied at VitB12 delivery are at the initial phase and aim to simplify administration, reduce costs, improve pharmacok...
Organic/inorganic hybrid nanomaterials with vitamin B12functions
Science and Technology of Advanced Materials, 2006
A hybrid nanomaterial was prepared by human serum albumin (HSA) and vitamin B 12 derivatives. The incorporation of hydrophobic vitamin B 12 derivatives, which have ester groups in place of the peripheral amide moieties of the natural cobalamin, into HSA is primarily controlled by the hydrophobicity of the peripheral ester groups. Microenvironmental property around the hydrophobic vitamin B 12 in HSA was examined by fluorescence and fluorescence polarization measurements. The hydrophobic vitamin B 12 itself in HSA is in a microenvironment equivalent in medium polarity to dichloromethane. The molecular motion of hydrophobic vitamin B 12 in HSA was markedly suppressed under such microenvironmental conditions. Carbon-skeleton rearrangement reaction of an alkyl radical derived from an alkyl ligand bound to the hydrophobic vitamin B 12 was markedly favored in HSA aqueous solution, relative to the reactions in methanol and benzene. The 1,2-migration of the electron-withdrawing group arises from both the suppression of molecular motion and desolvation effects on the alkylated hydrophobic vitamin B 12 in HSA.
Colloids and surfaces B: Biointerfaces, 2019
Targeted delivery of vitamins to a desirable area is an active branch in a modern pharmacology. The most important and difficult delivery of vitamin B12 is that to bone marrow and nerve cells. Herein we present a first step towards the development of two types of smart carriers, polymer capsules and lyotropic liquid-crystalline nanosystems, for vitamin B12 targeted delivery and induced release. A vitamin B12 encapsulation technique into nanoengineered polymeric capsules produced by layer-by-layer assembling of polymeric shells on CaCO3 templates has been developed. The effectiveness of the process was demonstrated by optical absorption spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM) and small-angle X-ray diffraction. TEM and AFM analyses performed on capsules after their drying, confirmed the presence of the vitamin B12 inside the capsules in the form of crystalline nanoaggregates, 50-300 nm in diameter. Soft lipid nanovectors consisting of amphiphilic phytantriol molecules, which in water excess spontaneously self-assembly in 3D well-ordered inverse bicontinuous cubic bulk phase, were used as alternative carriers for vitamin B12. It was shown that about 30% of the vitamin added in the preparation of the soft lipid system was actually encapsulated in cubosomes and that no structural changes occurred upon loading. The Vitamin stabilizes the lipid system playing the role of its structure-forming element. The biocompatible nature, the stability and the feasibility of these systems make them good candidates as carriers for hydrophilic vitamins.
Biotechnology of Nanostructures Micronutrients Vitamins for Human Health
Journal of Biomedical Research & Environmental Sciences, 2021
Nowadays, nanotechnology is used as a way to increase bioavailability and decrease the side effects of drugs and nutrients. Micronutrients and nutraceuticals such as vitamins, carotenoids, polyunsaturated fatty acids and polyphenols are classes of food ingredients that are essential for human health and well-being. These compounds are rarely added purely to the targeted food application but rather in encapsulated, solid, dry product forms with added functionalities such as improved stability, bioavailability or handling. Development of new strategies, like nanocarriers, that help to promote the access of neuroprotective molecules to the brain, is needed for providing more effective therapies for the disorders of the Central Nervous System (CNS). Polymer–lipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications. Recently, nano...
Molecules
In this overview, the latest achievements in dietary origins, absorption mechanism, bioavailability assay, health advantages, cutting-edge encapsulation techniques, fortification approaches, and innovative highly sensitive sensor-based detection methods of vitamin B12 (VB12) were addressed. The cobalt-centered vitamin B is mainly found in animal products, posing challenges for strict vegetarians and vegans. Its bioavailability is highly influenced by intrinsic factor, absorption in the ileum, and liver reabsorption. VB12 mainly contributes to blood cell synthesis, cognitive function, and cardiovascular health, and potentially reduces anemia and optic neuropathy. Microencapsulation techniques improve the stability and controlled release of VB12. Co-microencapsulation of VB12 with other vitamins and bioactive compounds enhances bioavailability and controlled release, providing versatile initiatives for improving bio-functionality. Nanotechnology, including nanovesicles, nanoemulsions,...
Vitamin B12 (Cobalamin) and Micronutrient Fortification in Food Crops Using Nanoparticle Technology
Frontiers in Plant Science, 2021
It is necessary to develop a resilient food supply that will withstand unexpected future shocks and deliver the required amounts of nutrients to consumers. By increasing the sustainability of food and agriculture, the food system will be able to handle challenges such as climate change, declining agricultural resources, growing population/urbanization, pandemics, and recessions/shortages. Micronutrient deficiency, otherwise called hidden hunger, is one of the major malnutrition consequences worldwide, particularly in middle- or low- income countries. Unlike essential mineral or nutrient compounds, micronutrients could be less of a priority due to their small levels of requirement. However, insufficient micronutrients caused critical adverse health symptoms and are excessively vital for young children’s development. Therefore, there have been numerous attempts to enhance minerals and nutrients in food crops, including biofortification, food fortification, and supplementation. Based o...
The pH-Dependent Controlled Release of Encapsulated Vitamin B1 from Liposomal Nanocarrier
International Journal of Molecular Sciences
In this work, we firstly presented a simple encapsulation method to prepare thiamine hydrochloride (vitamin B1)-loaded asolectin-based liposomes with average hydrodynamic diameter of ca. 225 and 245 nm under physiological and acidic conditions, respectively. In addition to the optimization of the sonication and magnetic stirring times used for size regulation, the effect of the concentrations of both asolectin carrier and initial vitamin B1 on the entrapment efficiency (EE %) was also investigated. Thermoanalytical measurements clearly demonstrated that after the successful encapsulation, only weak interactions were discovered between the carriers and the drug molecules. Moreover, the dissolution profiles under physiological (pH = 7.40) and gastric conditions (pH = 1.50) were also registered and the release profiles of our liposomal B1 system were compared with the dissolution profile of the pure drug solution and a manufactured tablet containing thiamin hydrochloride as active ingr...
A novel vitamin B12-nanosphere conjugate carrier system for peroral delivery of insulin
Journal of Controlled Release, 2007
In spite of great potential, effective oral delivery of many vitamin B 12-peptide/protein drug conjugates does not occur due to the limited uptake capacity of the VB 12 transport system, loss of bioactivity of native protein and/or intrinsic factor affinity of VB 12 and liability to GI degradation. In order to overcome these shortcomings in a two pronged way, we have endeavoured to develop a VB 12-Nanoparticles (NPs) system to enhance the uptake capacity of both NPs and VB 12 transport to deliver orally effective insulin. NPs were prepared using different molecular weight dextrans and epichlorohydrin as cross-linker by an emulsion method. NPs surface was modified with succinic anhydride, and conjugated with amino VB 12 derivatives of carbamate linkage. VB 12 attachment was confirmed by IR, XPS analysis, and was quantified by HPLC (4.0 to 4.4% w/w of NPs). The pre-formed NPs conjugates (Zave = 160-250 nm; polydisperse) were loaded with 2, 3 and 4% w/w of insulin, and the entrapment was found to be 45-70%. NPs conjugates were found to protect 65-83% of entrapped insulin against in vitro gut proteases. In vitro release studies exhibit an initial burst followed by diffusion controlled first order kinetics with 75-95% release within 48 h. After oral administration of these carriers (20 IU/kg), a nadir of 70-75% reduction in plasma glucose was found in 5 h, reached basal levels in 8-10 h, and a prolonged second phase was found until 54 h. The % pharmacological availability (PA) of 70 K NPs conjugate containing 2, 3 and 4% w/w insulin was 1.1, 1.9 and 2.6 fold higher, respectively compared to NPs without VB 12 ; consistent with the hypothesis that uptake was mediated by the vitamin B 12 transport. NPs of 70 K dextran showed 1.4 fold PA compared to 10 K while negligible action was observed with 200 K. The potential utilities of VB 12-NPs carrier as an oral delivery platform of proteins, especially insulin via dextran-coated particles necessities further elaborate investigations.
Polymer International, 2008
BACKGROUND: Vitamin B12 is an essential vitamin required by all mammals. Absorption of vitamin B12 is facilitated by binding of intrinsic factor-vitamin B 12 complex to specific receptors in the ileum. In humans a deficiency of this vitamin or a lack of intrinsic factor leads to pernicious anaemia. The major objective of the present study was to prepare intrinsic factor-vitamin B12 complex-loaded poly[lactic-co-(glycolic acid)] (PLGA)-based microparticles and to investigate their release kinetics. RESULTS: PLGA copolymer was synthesized by the ring-opening polymerization method and characterized using gel permeation chromatography, Fourier transform infrared spectroscopy and 1 H NMR. The glass transition temperature measurement showed a single T g at 40 • C. The intrinsic factor-vitamin B12 complex-loaded PLGA microspheres were prepared by a water-in-oil-in-water double emulsion solvent extraction/evaporation technique. An environmental scanning electron microscopy investigation demonstrated that the PLGA particles had a mean particle diameter of 38 µm. Interestingly, different drug release patterns (bi-and triphasic ones) were observed for vitamin B12-loaded and intrinsic factor-vitamin B12 complex-loaded microspheres. In contrast to the rapid release of vitamin B12 by itself, in vitro release tests showed that intrinsic factor and vitamin B12 in the complex were released from PLGA microspheres in a sustained manner over 15 days. CONCLUSION: PLGA microspheres can be an effective carrier for the intrinsic factor-vitamin B12 complex.