Self-aggregating long-acting injectable microcrystals
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<sup>-1</sup>). 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.
Authors
- Adolfo Guevara (ORCID: https://orcid.org/0000-0001-5366-372X)
- Giovanni Battista Traverso (ORCID: https://orcid.org/0000-0001-7851-4077)
- Jia Liang (ORCID: https://orcid.org/0000-0003-3697-3528)
- Santiago González (ORCID: https://orcid.org/0000-0003-4166-7664)
- Niora Fabian (ORCID: https://orcid.org/0000-0001-5871-0206)
- Jason Li (ORCID: https://orcid.org/0000-0002-5594-6448)
- Ashka Patel (ORCID: https://orcid.org/0009-0004-6128-5510)
- Benjamin Muller (ORCID: https://orcid.org/0000-0003-1338-7737)
- Gary W. Liu (ORCID: https://orcid.org/0000-0001-5862-1019)
- Mark W. Tibbitt (ORCID: https://orcid.org/0000-0002-4917-7187)
- Vivian R. Feig (ORCID: https://orcid.org/0000-0001-6144-0868)
- Andrew Pettinari
- Pier Giuseppe Rivano (ORCID: https://orcid.org/0009-0005-9568-7291)
- Jinhee Kim (ORCID: https://orcid.org/0000-0002-0732-1398)
- Sanghyun Park (ORCID: https://orcid.org/0000-0002-4336-2621)
- Aaron Lopes
- Flavia Codreanu
- Hannah Carlisle
- Ayten E. Erdogan
- Caroline Dial
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Northeastern University (US)
- Harvard University (US)
- University of Toronto (CA)
- ETH Zurich (CH)
- Massachusetts Institute of Technology (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Chemical Engineering
- Published
- 2025-03-24
- DOI
- https://doi.org/10.1038/s44286-025-00194-x
- Citations
- 13
- Primary Topic
- Pickering emulsions and particle stabilization
- Type
- article
- Field-Weighted Citation Impact
- 6.73
Funders
- Bill and Melinda Gates Foundation
- Massachusetts Institute of Technology
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- Kwanjeong Educational Foundation
- Natural Sciences and Engineering Research Council of Canada
- National Cancer Institute
- Division of Materials Research