Oral Delivery of Multicompartment Nanomedicines for Colorectal Cancer Therapeutics: Combining Loco‐Regional Delivery with Cell‐Target Specificity

Abstract

AbstractNanomaterials for targeted delivery of chemotherapeutics have received significant attention owing to their potential to enhance the accumulation of therapeutics in diseased tissue. However, in diseases with poor vascularization, such as colorectal cancer (CRC), intravenously injected materials have reduced access to the site of interest. To overcome this challenge, oral administration of targeted nanomedicines is highly desirable. Here, a multicomponent drug delivery system incorporating a degradable alginate microcapsule, formulated to encapsulate micelles targeted to the CD44 receptor is presented. Functional micelles are generated by coupling hyaluronic acid (to target CD44 receptor) to block copolymers of poly(ethylene glycol) monomethyl ether methacrylate and poly(methyl methacrylate). When encapsulated into alginate microcapsules, these micelles form the basis of a novel oral delivery system that offers protection from degradative compartments of the gastrointestinal tract (GIT) and regio‐specific release. The microcapsules demonstrate desirable site‐specific degradation properties in an orthotopic CRC xenograft mouse model, yielding enhanced accumulation of micelles within CD44+ colorectal tumors. The results illustrate that such materials successfully navigate the GIT, regio‐specifically release targeted micelles at the tumor site, and consequently accomplish enhanced accumulation within tumor tissue. Such multi‐component nanomaterials offer a promising means for addressing challenges in treating CRC and difficult to treat diseases.