期刊
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
卷 50, 期 -, 页码 57-65出版社
ELSEVIER
DOI: 10.1016/j.jddst.2019.01.013
关键词
Acetalated dextran; 1,2-Dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS); Macrophage-associated diseases; Targeted cellular uptake; Nanoparticles; Drug delivery
资金
- Institutional Development Award (IDeA) Network for Biomedical Research Excellence from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103430]
- National Science Foundation EPSCoR Cooperative Agreement [EPS-1004057]
- National Science Foundation [1508868]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1508868] Funding Source: National Science Foundation
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 pHsensitive 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.
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