Design and engineering of biodegradable 3D nanoprinted microcarriers for HIV drug delivery - precise, customizable drug delivery remains a long-term goal, for HIV in particular, as such technologies…

Design and engineering of biodegradable 3D nanoprinted microcarriers for HIV drug delivery - precise, customizable drug delivery remains a long-term goal, for HIV in particular, as such technologies would allow therapies tailored to a patient's biological makeup and potentially improve adherence. Extended-release methods address part of the issue, but face limitations. A novel drug delivery system could offer better pediatric dosing, via both oral and new routes of administration. Existing extended-release methods are limited: industry standards for liquid-drug microcarrier fabrication are restricted by manufacturing-induced constraints, including: (i) limited micro-carrier geometries; (II) undesired carrier-to-carrier variability; (III) difficult means of multidrug microcarrier production; and (IV) exceedingly impractical pathways to on-demand modifications of microcarrier architectures and compositions. Rapid multi-material three- dimensional (3D) nanoprinting of liquid-filled microcontainers offers the potential to revolutionize the production of therapeutic microcarriers by addressing the aforementioned pain points via: (i) unparalleled 3D versatility in microcarrier design, (II) 100-NM-scale feature resolution, (III) rapid, multi-material production, and (IV) on-demand customization of each individual microcarrier. Proof of concept has been demonstrated by printing 3D microcontainers the size of human epithelial cells comprising standard (i.e., non-biological) photoresists encompassing an aqueous fluid. The current focus is to engineer microcarriers based on biocompatible and biodegradable materials, with microcarrier architectures composed of: (1) a biodegradable outer "shell" with an orifice on top, (2) a core of (at least one) therapeutic liquid "payload", and (3) a custom-designed biodegradable "cap" atop the shell. At scale, this strategy could produce extended-release microcarriers, with each cap design (and thus, biodegradation dynamics) offering distinct, targeted release kinetics. Improved stability and non-accumulation are additional advantages. The proposed multi-material microcarriers with design-based release properties bridge an important need, especially for HIV. The innovation of liquid-filled microcarriers with tailor-made architectures and compositions at this scale offers precision dosing and therapeutic options- e.g., combination therapies and release rate controls-not otherwise achievable. The work will investigate the proposed strategy for designing and engineering 3D multi-material microcarriers for ultra-extended-release therapeutic uses.