Highlights

• This study pioneers the use of leonurine nanocrystals encapsulated in PLGA microspheres for long-term management of hyperlipidemia.
• The study successfully achieves high drug loading and sustained release by optimizing multiple formulation variables including pH modifiers and osmotic pressure.
• The injectable microspheres formulation allows dosing once every two weeks, while effectively maintaining lipid-lowering efficacy.

Summary

This study presents an injectable system of leonurine nanocrystals encapsulated in PLGA microspheres (Leo-nano@MP) as a  potential long-term treatment for hyperlipidemia.

Through systematic optimization of formulation parameters, the authors obtained microspheres with high drug loading and demonstrated sustained in vitro release over 20 days, primarily governed by a combination of diffusion and matrix erosion. In a high-fat diet rat model, subcutaneous administration of Leo-nano@MP once every two weeks significantly improved  serum lipid profiles and mitigated liver and kidney injury, outperforming daily administration of daily dosing with free leonurine. The formulation also exhibited favorable pharmacokinetics, maintaining prolonged plasma drug levels, and showed no signs of toxicity or inflammation in major organs or at injection sites.

Overall, Leo-nano@MP offers a promising alternative to conventional statin therapies by enabling reduced dosing frequency with enhanced therapeutic efficacy and improved safety profile, highlighting its potential for clinical translation.

Song Z, Meng S, Tang Z, Yang X, He Y, Zheng Y, Guo H, Du M, Zhu Y, Wang X. Injectable leonurine nanocrystal-loaded microspheres for long-term hyperlipidemia management. Biomater Sci. 2023 Jun 27;11(13):4713-4726. doi: 10.1039/d3bm00211j.