Enhancement of macrophage uptake via phosphatidylserine-coated acetalated dextran nanoparticles
Date of Original Version
Although vital to the immune system, macrophages can act as reservoirs for pathogens such as tuberculosis and human immunodeficiency virus. Limitations in the treatment of such diseases include targeting therapeutics directly to macrophages and the large systemic dosages needed. The objective of this study is to develop a nanoparticle (NP)-based drug delivery system that can provide targeted delivery into macrophages. Acetalated dextran (Ac-Dex) NP loaded with the lipophilic model compound curcumin (CUR) were synthesized and coated in 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine (DPPS), a phospholipid that induces phagocytosis in macrophages. DPPS-CUR NP were found to release 67.8% of encapsulated CUR within 24 h at pH 5.35 and exhibited minimal CUR release (6.3%) at pH 7.4. DPPS-CUR NP were uptaken by murine macrophages significantly more than NP without DPPS coating and NP exposure to these macrophages resulted in minimal toxicity to the cells and minimal nitric oxide production. These results suggest that the combination of the DPPS coating and pH-sensitive polymer Ac-Dex can provide a NP delivery system capable of enhanced uptake by macrophages and potential systemic stability to more effectively deliver drugs of interest. As a result, the described DPPS-CUR NP can serve as a viable delivery system for the treatment of macrophage-associated diseases.
Shah, N. K., Gupta, S. K., Wang, Z., & Meenach, S. A. (2019). Enhancement of macrophage uptake via phosphatidylserine-coated acetalated dextran nanoparticles. Journal of Drug Delivery Science and Technology, 50, 57-65. doi: 10.1016/j.jddst.2019.01.013
Available at: https://doi.org/10.1016/j.jddst.2019.01.013
Nishan K. Shah is a graduate assistant in the Department of Biomedical and Pharmaceutical Sciences. Sweta K. Gupta and Zimeng Wang are in the Department of Chemical Engineering. Samantha A. Meenach has a dual appointment with the Department of Biomedical and Pharmaceutical Sciences and the Department of Chemical Engineering.
This is a pre-publication author manuscript of the final, published article.
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