Rahim Rahimi1
Purdue University1
Oral administration of therapeutics is the most common approach of drug delivery due to its safety, low cost and good compliance. However, proper absorption and bioavailability of the therapeutics is highly important for the efficacy of drugs. It is estimated that over 40% of all candidate drugs are abandoned due to some form of adverse pharmacokinetics and bioavailability during clinical trials. Recent studies have shown that the drug efficacy is not only dependent on the drug physiochemistry and host physiology but also by the collection of microorganisms that are present in the GI tract, also referred to as the human gut microbiome. The gut microbiome is comprised of over 100 trillion microbes residing within the GI track, which function in an intimate symbiotic relationship with the host. Healthy and normal gut microbiome take an essential part in the digestion of food ingredients to produce the required vitamins and metabolites to modulate the hosts immune system. However, one of the critical and most overlooked factors is the metabolic activity that the gut microbiome could have on orally administered drugs and modulating their bioavailability. Interestingly, while individual humans have approximately 99% identical genomes, there is a high level of diversity in the gut microbiome, which on average can be greater than 90% different between healthy individuals at the same age. In addition, there has been interesting discoveries linking the composition and abundance of certain types of gut microbiome to many diseases including inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, autoimmune conditions, diabetes and cholesterol.<br/>These findings suggest that orally administered therapeutic can be more effective by knowing the composition and profile of the host microbiome and making appropriate adjustments into the therapeutics for personalized medication. Over the past few years, new advancements in additive manufacturing technologies have allowed the rapid and cost-effective construction of desired therapeutics for personalized medication and emerging reality. Furthermore, such technologies have enabled constructing objects with various complex shapes and materials that were not possible through conventional mass-produced approaches. This unique feature not only allows to rapidly adjust the therapeutic dosage but also the geometry and structure of the capsule (e.g., size, porosity) for the indented application and user (e.g., humans or animals). Furthermore, the unique customization of materials used in the structure of the printed device allows the possibility to create more advanced and smart devices that are beyond drug delivery applications.<br/>In this talk I will discuss the new possibility of using additive manufacturing technologies to construct novel customizable low-cost smart capsule devices that will allow targeted sampling and assessment of the microbiome profile throughout the GI tract. The capsule can provide new insights into the presence of specific bacterial species within the microbiome that could potentially alter the metabolism of certain drugs and help in making more informed decisions in personalized medications. In the first part of this talk I will describe the construction of a novel battery-less customizable capsule designs with targeted activation locations in the GI tract by utilizing multi-functional pH sensitive and super absorbent polymers in the structure of the capsule. Building upon this platform, I will also present our recent progress in further decreasing form factor of the capsules using standard stereo lithography 3D printing, and their scaling-up for animal studies. I will finally discuss our on-going efforts in utilizing the customization of 3D printed smart sampling capsule, which is being used in animal studies to assess the effect of dietary changes on the microbial metabolites and GI related disease status.