MAR 31, 2025 11:10 AM PDT

Drug Delivery System Under the Skin

WRITTEN BY: Greta Anne

The development of long-acting drug depots represents a significant advancement in pharmaceutical technology, offering controlled release formulations that enhance patient compliance and therapeutic efficacy. A study published in Nature explores the mechanical and biochemical properties of subcutaneous depots, aiming to optimize drug release profiles across different injection sites and animal models to better predict human applications.

This study primarily focused on levonorgestrel (LNG), a widely used contraceptive drug, but the findings suggest that the formulation approach may be applicable to other hydrophobic drugs. Given that a significant proportion of new pharmaceutical compounds exhibit poor solubility in physiological fluids, this platform has the potential to address a critical industry challenge. 

To develop these long-acting formulations, researchers prepared LNG depots using a FlackTek Speedmixer to homogenize LNG powder with solvent or polymer solutions. The formulations were allowed to equilibrate to ensure saturation, followed by vortexing before use. The in vitro characterization involved macroscale time-lapse imaging, contact angle measurements, and advanced microscopy techniques, including scanning electron microscopy (SEM) and powder X-ray diffraction (XRD). These analyses provided insights into the physicochemical behavior of the drug depots, confirming the self-aggregation properties and dissolution kinetics of LNG microcrystals.

Beyond mechanical characterization, an initial toxicity assessment was performed in animal models. Female Sprague–Dawley rats were injected with various solvent carriers, including benzyl benzoate (BB), benzyl alcohol (BA), and phosphate-buffered saline (PBS), at different dosages. The animals were monitored for acute and chronic toxicity markers, including weight loss and systemic effects. Histopathological analysis of tissues from the injection site, liver, kidney, spleen, and heart provided a comprehensive safety evaluation. The results demonstrated that the selected carriers were well tolerated, supporting the feasibility of this approach for human applications.

Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital (BWH), an associate member of the Broad Institute, and the senior author of the study, highlights the simplicity and adaptability of the system: “This is a very simple system in that it’s basically a solvent, the drug, and then you can add a little bit of bioresorbable polymer. Now we’re considering which indications do we go after: Is it contraception? Is it others? These are some of the things that we’re starting to look into as part of the next steps toward translation to humans.”  

A pharmacokinetic study was also conducted over 97 days to evaluate the serum concentrations of LNG released from various formulations. Blood samples were collected at predetermined intervals and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). This analysis confirmed the sustained release profile of LNG, reinforcing the potential of this delivery system for extended therapeutic applications.

As the research progresses, future work will explore how different drugs interact with the in-situ aggregation mechanism and how the depot characteristics may be tailored to optimize therapeutic outcomes. The potential applications extend beyond contraception to include treatments for chronic diseases requiring long-term medication adherence.

Sources: Nature, EurekAlert

About the Author
Doctor of Pharmacy (PharmD)
Greta holds her PharmD and is a writer at Labroots. She also has a strong background in neuroscience & psychology. When she is not working as a pharmacist or a writer, she enjoys fostering her creative initiatives such as traveling, working out, spending time at the beach, and cooking!
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