In-vivo Intradermal Delivery of Co-57 labeled Vitamin B-12, and Subsequent Comparison with Standard Subcutaneous Administration *

摘要

Vitamin B-12 (cobalamin) deficiency in humans is a worldwide problem emanating from varied causes such as insufficient dietary intake or malabsorption of the micronutrient due to an underlying condition (absence or failure of intrinsic factor, atrophic gastritis, post-operative bariatric surgery, inflammatory bowel disease, cobalt deficiency etc.). As oral supplementation is limited by its bioavailability due to the absorptive property of intrinsic factor, clinicians often prescribe parenteral forms of administration to replenish diminished levels rapidly. The gold standard in parenteral delivery of cobalamin is subcutaneous and/or intramuscular injections. The relatively large molecular size of cobalamin (1355.39 Da) makes passive transdermal patch-based delivery via the stratum corneum quite challenging. Hence, the primary goal of this study is to investigate the feasibility of intradermal (ID) delivery of Vitamin B-12 via an almost painless microneedle injection and subsequent comparison with standard subcutaneous (SC) delivery. This work reports on a custom-made microneedle device built from a commercial insulin needle and it’s use to perform ID delivery of Co-57 radiolabeled Vitamin B-12 in-vivo in rabbits. The pharmacokinetic profile and bioavailability were studied and compared with SC delivery. It is the first comprehensive study, to our best knowledge, that compares a micronutrient (eg. Vitamin B-12) delivery via ID and SC routes in-vivo. While the bioavailability for the SC route is found to be slightly higher compared to the ID route (99% vs. 96%), the Tmax for both are almost identical. Thus, ID delivery of Vitamin B-12 using a microneedle injection could be a viable and minimally invasive alternative to existing parenteral options.