Self-aggregating long-acting injectable microcrystals.
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Abstract | Injectable drug depots have transformed our capacity to enhance medication adherence through dose simplification. Central to patient adoption of injectables is the acceptability of needle injections, with needle gauge as a key factor informing patient discomfort. Maximizing drug loading in injectables supports longer drug release while reducing injection volume and discomfort. Here, to address these requirements, we developed self-aggregating long-acting injectable microcrystals (SLIM), an injectable formulation containing drug microcrystals that self-aggregate in the subcutaneous space to form a monolithic implant with a low ratio of polymer excipient to drug (0.0625:1 w/w). By minimizing polymer content, SLIM supports injection through low-profile needles (<25 G) with high drug loading (293 mg ml). We demonstrate in vitro and in vivo that self-aggregation is driven by solvent exchange at the injection site and that slower-exchanging solvents result in increased microcrystal compaction and reduced implant porosity. We further show that self-aggregation enhances long-term drug release in rodents. We anticipate that SLIM could enable low-cost interventions for contraceptives. |
Year of Publication | 2025
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Journal | Nature chemical engineering
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Volume | 2
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Issue | 3
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Pages | 209-219
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Date Published | 12/2025
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ISSN | 2948-1198
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DOI | 10.1038/s44286-025-00194-x
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PubMed ID | 40144331
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