Design and Engineering of Biodegradable 3D Nanoprinted Microcarriers for HIV Drug Delivery

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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.