Authors
Shamima Zaman, Grant Swajian, Shiril Bhardwaj Iragavarapu, Md Tashdid Hossain Shoudho, Bahman Anvari
Published in
Journal of biomedical materials research. Part A. Volume 114. Issue 6. Pages e70109.
Abstract
Erythrocyte-derived carriers have emerged as effective biomimetic platforms for the delivery of therapeutic and imaging cargos. However, clearance by the mononuclear phagocytic system (MPS) limits their utility. Towards development of standardized methods for increased bioavailability, we have developed an approach that lowers the externalization of phosphatidylserine (PS), a biomarker for MPS clearance, to the outer leaflet of the membrane. Specifically, this approach minimizes the hypotonic treatment of erythrocytes to a single cycle for depleting the hemoglobin while enriching the membrane bilayer with cholesterol during depletion, and in the subsequent cargo loading step, using indocyanine green (ICG), a fluorescent probe as an illustrative cargo. Using this strategy, PS externalization remains limited to ~16% and 9% of the carrier system with and without the encapsulated ICG, respectively, compared to ~46%-99% following multiple hypotonic cycles without cholesterol enrichment. Carriers engineered using this method exhibit significantly reduced macrophage uptake in vitro. In vivo biodistribution studies in healthy mice show ~2.7-fold increase in blood-associated fluorescence, and ~3.3-fold decrease in splenic accumulation after intravascular injection relative to carriers formed by multiple cycles of hypotonic treatment and without cholesterol enrichment. This method provides an effective approach to improve the circulatory retention of erythrocyte-based carriers.
PMID:
42295139
Bibliographic data and abstract were imported from PubMed on 15 Jun 2026.
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