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.Innovation in ultra-extended-release therapeutic microcarriers, constructed via novel submicron-
scale multimaterial 3D printing technology, enables better dosing, which minimizes toxicity and
yields better adherence.
Currently, polymer and lipid-based nanocarriers are used for accurate dosing of highly potent,
poorly soluble drugs or fragile biomolecules, but the proposed physical fill of a biodegradable
microcarrier is simpler than competing technologies requiring molecular interaction, and offers
new options for HIV combination therapy and variable release rates.
This work expands on the team’s preliminary foundation, to optimize cap thickness and
geometry for precision drug release.