Exploiting the Vitamin B₁₂ Pathway To Enhance Oral Drug Delivery via Polymeric Micelles

Abstract

Vitamin B12 (VB12)-modified dextran-g-polyethyleneoxide cetyl ether (DEX-g-PEO-C16) was synthesized by linking VB12 residues to a DEX-g-PEO-C16 copolymer via a 2,2'-(ethylenedioxy)bis(ethylamine) spacer. The level of VB12 substitution on the DEX-g-PEO-C16 copolymer reached 1.68% (w/w). In aqueous solution, DEX-based copolymers form micelles that can entrap within their hydrophobic core up to 8.5% w/w of cyclosporin A (CsA), a poorly water soluble immunosuppressant. The permeability of Caco-2 cell membranes to CsA incorporated in VB12 modified and unmodified polymeric micelles was monitored in the presence and absence of intrinsic factor (IF). The apical (AP) to basolateral (BL) permeation of CsA through Caco-2 cell monolayers after 24 h of transport was significantly higher (1.8 and 2.3 times in absence and presence of IF, respectively) in the case of CsA loaded in VB12-modified polymeric micelles, compared to CsA in unmodified micelles. The results point to possible improvement in the application of polysaccharide-based polymeric micelles as targeted polymeric drug carriers for the oral delivery of poorly water soluble drugs.

Nicotinamide polymeric nanoemulsified systems: a quality-by-design case study for a sustained antimicrobial activity

“…Amphiphilic block copolymer with its aqueous and organic moieties can form nanoemulsions in aqueous medium through the self-molecular interactions to entrap the hydrophobic medications in the central portion of micelles. 13 These novel delivery systems have been successfully employed with various medications such as anticancer drugs, 14 immunosuppressants, 11 vitamins, 15 and others to improve their therapeutic efficacy. Eudragit ® S100 is an anionic copolymerization product of methacrylic acid to methyl methacrylate in the ratio of 1:2.…”

Evaluation of Bioadhesive Capacity and Immunoadjuvant Properties of Vitamin B12-Gantrez Nanoparticles

“…They have clearly demonstrated the effective cellular uptake of nanoparticles (7) or polymeric micelles containing cyclosporine A coated with vitamin B 12 (8). Recently, in vivo results indicated the beneficial use of vitamin B 12 -coated dextran nanoparticles for the oral delivery of insulin (9).…”

Nanodrugs: pharmacokinetics and safety

“…10 Strategic functionalization with some membrane permeation enhancers or ligands for receptors expressed on the cellular membrane may also promote the transcellular transport of entrapped drugs. 11,12,15 In addition to transcellular transport, nanodrugs equipped with bioadhesive polymers or chelators could enhance the paracellular transport of entrapped drugs, via the regulation of tight junctions. 16,17 Surface modification of nanodrugs, with specific proteins, antibodies, and other biomolecules, can be used to design drugs that act selectively on particular tissues, 18 and this approach has been employed to provide improved therapeutic potential and reduced side effects of some anticancer drugs.…”