Vitamin B12 In Drug Delivery: Breaking Through The Barriers To A B12 Bioconjugate Pharmaceutical

In press in Expert Opinion On Drug Delivery (DOI:10.1517/17425247.2011.539200). The theory section (the only part I can properly speak to) builds on the discussion section of the full theory paper in Molecular Biosystems from earlier this year, providing an outlet for some of the more speculative design possibilities for trinary B12 bioconjugate design. Given that (1) there are mechanisms for cleavage at both of the proposed positions and (2) the molecular dynamics work indicates that, at least, TCII (transcobalamin II) can easily accommodate a bi-functionalized cobalamin, the A-B12-C design possibility is probably the most interesting long-term idea to come out of the computational side of the B12-insulin bioconjugate study (or so I argue).

Having “B12” and “cobalamin” in a blog post guarantees a bunch of useless moderation-necessary comments from vita-spam sites.

Susan M. Clardy, Damian G. Allis, Timothy J. Fairchild & Robert P. Doyle

Syracuse University, Syracuse, Department of Chemistry, NY 13244-4100, USA

Importance of the field: Vitamin B12 (B12) is a rare and vital micronutrient for which mammals have developed a complex and highly efficient dietary uptake system. This uptake pathway consists of a series of proteins and receptors, and has been utilized to deliver several bioactive and/or imaging molecules from 99mTc to insulin.

Areas covered in this review: The current field of B12-based drug delivery is reviewed, including recent highlights surrounding the very pathway itself.

What the reader will gain: Despite over 30 years of work, no B12-based drug delivery conjugate has reached the market-place, hampered by issues such as limited uptake capacity, gastrointestinal degradation of the conjugate or high background uptake by healthy tissues. Variability in dose response among individuals, especially across ageing populations and slow oral uptake (several hours), has also slowed development and interest.

Take home message: This review is intended to stress again the great potential, as yet not fully realized, for B12-based therapeutics, tumor imaging and oral drug delivery. This review discusses recent reports that demonstrate that the issues noted above can be overcome and need not be seen as negating the great potential of B12 in the drug delivery field.

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