Abstract
Nanoparticle-based therapeutics hold promise for the treatment of atherosclerosis, but challenges such as low drug-loading capacity and a lack of scalable, controllable production hinder their clinical translation. Flash nanoprecipitation, a continuous synthesis method, offers a potential solution for scalable and reproducible nanoparticle production. In this study, we employed a custom-designed multi-inlet vortex mixer to perform cross-linking reaction-enabled flash nanoprecipitation, facilitating controlled and scalable synthesis of cross-linked Poly amidoamine (PAMAM) dendrimer nanoparticles. Notably, this approach allows simultaneous nanoparticle cross-linking and drug loading in a single step. The mannose moiety enabled specific targeting of macrophages via mannose receptors, enhancing the localization of the nanoparticles to atherosclerotic plaques. Atorvastatin calcium, a widely used clinical drug for atherosclerosis treatment, was selected as the model drug. This approach achieved both high production rates and high drug-loading capacities, with an output flow rate of 9.6 L/h and a nanoparticle concentration of approximately 0.4 g/L. The optimized formulation exhibited a drug-loading capacity of 37% and an encapsulation efficiency of 76%. In vitro and in vivo experiments demonstrated effective macrophage and plaque targeting, leading to significant therapeutic benefits. Treatment with these nanoparticles resulted in approximately 40% inhibition of aortic root plaque progression compared to the free drug-treated group. This scalable and efficient nanoparticle platform is a promising strategy for improving atherosclerosis treatment.
Recommended Citation
H. Kou et al., "Scalable Fabrication of High-Payload Dendrimer-Based Nanoparticles for Targeted Atherosclerosis Therapy," ACS Applied Materials and Interfaces, American Chemical Society, Jan 2025.
The definitive version is available at https://doi.org/10.1021/acsami.5c00816
Department(s)
Chemistry
Second Department
Chemical and Biochemical Engineering
Keywords and Phrases
atherosclerosis; flash nanoprecipitation; mannose; multi-inlet vortex mixer; PAMAM dendrimer
International Standard Serial Number (ISSN)
1944-8252; 1944-8244
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2025 American Chemical Society, All rights reserved.
Publication Date
01 Jan 2025
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biomedical Engineering and Bioengineering Commons, Chemical Engineering Commons, Chemistry Commons
Comments
National Institutes of Health, Grant R01HL140684