| Project Detail |
We propose to use human breast milk cells to engineer breast milk biomimetic nanoparticles (NP), “MILKOSOMES,” to shuttle medicines orally into the body that, under other conditions, would not be able to distribute properly. MILKOSOMES are cellular membrane protein-functionalized phospho-lipid NP (i.e. liposomes), and they are hypothesized to cross the gastrointestinal (GI) tract while protecting their therapeutic cargo and serve as a novel way to improve oral therapy outcomes. Unfortunately, although oral delivery of therapeutic agents is the most patient-preferred route of administration because it is painless and convenient, it entails enormous challenges. Specifically, large molecules, such as messenger RNA and proteins, cannot be delivered orally due to their chemical and enzymatic degradation in the GI tract and poor intestines permeability to these molecules. Interestingly, cells, which are a thousand times bigger than these large molecules, remain intact. Therefore, they can get out of the GI tract due to membrane protein-mediated biological processes and make their way into our bodies. Herein, we aim to: (1) Identify and assess the breast milk cell populations which cross the GI tract into the infant body after breastfeeding in vivo, (2) Fabricate and characterize MILKOSOMES, (3) Evaluate MILKOSOMES’ ability to cross the GI tract biological barrier using in vitro and ex-human models, and (4) Test MILKOSOMES’ therapeutic efficacy in vivo using two diverse in vivo models. Thus, we will harness the specific and unique biological function of these GI tract-crossing native cells while protecting their therapeutic cargo from degradation using the phospho-lipid NP backbone. Our findings will increase our fundamental understanding of cellular and NP trafficking through the GI tract and lay the foundations for designing a next generation and non-invasive nano-biomimetic oral drug delivery technology that may affect public health worldwide. |
