Transdermal delivery of micronutrients through fortified body oil and cosmetics: a potential roadmap for future scale up

Abstract

The initial challenge was to address micronutrient deficiency in early childhood, an important determinant of poor neurocognitive development(1,2). The innovation selected for transdermal delivery of micronutrients has been scaled up from laboratory-level into clinical trials. It has now received a buy-in from the industry as well as from public health programs and next challenge is to ensure a continuous and sustainable scaling pathway.Although iron and folate oral supplementation in under-five children is the strategy adopted by public health programs in India, poor absorption of iron, gastro-intestinal adverse effects associated with oral iron are drawbacks associated with the oral supplements leading to suboptimal adherence to the supplements (3,4). We developed an innovative intervention in the form of a liposomal encapsulated micronutrient fortified oil for supplementation of iron, vitamin B12, folate and vitamin D which can deliver micronutrients transdermally. The journey for development of the intervention has been described earlier using theory of change approach which reflects how the intervention of LMF oil was modified based on the learnings at each step (5). The intervention was evaluated in a community-based randomized controlled study which showed benefit in improving the vitamin D levels and partial efficacy in improving anemia (6).Despite the mixed results of the community-based research study, the intervention received good acceptability in the community. Importantly, there is keen interest and buy-in from the industry partner involved in the clinical trial scale up. We describe here a potential road map for evaluating this innovation further and scaling it up in the public health program using theory of change approach.The earlier work focused on translating a laboratory-level innovation in clinical trials through interinstitutional collaboration. While moving from academic research settings to more commercial and program environment, we need to understand the role of additional stakeholders in the entire processindustry, regulator, public health bodies. Considering the existing Indian regulations (7) for new drug development, there is need for comprehensive scientific evidence on this innovation through translational studies. The transdermal route of intervention is an innovative route of supplementation. There is limited information available about the exact mechanism of absorption of the ingredients from the skin (8). The extent of absorption in children cannot be completely predicted from animal studies as animal skin is different from human skin. Additionally, the formulation of the LMF oil may need changes in order to improve the shelf stability and ability to incorporate higher doses of micronutrients, especially iron. Due to these factors, more rigorous standardization and clinical evaluation of the intervention is needed before scaling it up.Figure 1 shows the potential roadmap for this innovation and includes the following phases:Lipid nanostructures can be a useful platform for transdermal delivery of micronutrients as they can reversibly fluidize the stratum corneum to deliver the entrapped substances into the deeper dermis and can be synthesized using food grade materials that are safe for human use (9). The previous work pilot translated the technology for encapsulation of iron, folic acid, vitamin B12, and vitamin D and its incorporation in body oil from a bench-level technology to clinical trial settings using frugal methods that did not involve use of any organic solvent (5). The future work will involve scaling it up further for large scale production. We plan to use lyophilisation methods for long term preservation and better stability of the liposomes. Presently, the manufacturing processes have been refined to deliver purely encapsulated micronutrients in liposomes, to avoid any residual free actives on the skin. Also, in order to incorporate higher doses of micronutrients, exploration of alternate formulations in the form of lotions and creams is planned.The technology has demonstrated safety and efficacy in in vitro and in vivo animal models for transdermal delivery of nutrients at supplemental doses. The technology has also demonstrated no irritation potential during irritation patch testing in healthy human volunteers (5). There is need for generation of more evidence on the transdermal penetration of micronutrients , i.e. iron, vitamin B12, folate and vitamin D. Evidence from the completed study shows there is scope for increasing the amounts of ferrous bisglycinate and vitamin D as the presently included doses resulted in partial efficacy , however were safe to administer especially in young infants (6). Modification of the dose will require more clear evidence on efficacy and safety from the pharmacokinetic studies in animals and humans. Additionally, we plan to utilise the bio-samples of the earlier study to evaluate the changes in the vitamin B12 and folate