Table 1. Comparison of erythrocytes with other drug delivery systems.
Note that half-life in circulation is shown for mice for the sake of consistency of the comparison (data for humans are not available for many drug delivery systems), whereas in humans RBC half-life is close to 60 days. Highly asymmetrical filomicelles have diameter of 40 nm and length ranging 1–30 micron. Size, shape and half-life in circulation vary immensely for proteins and protein conjugates. For example, protein molecules such as fibrinolytic plasminogen activators are small (<5 nm) and have very short half-life in the bloodstream (5–20 minutes), whereas immunoglobulins are slightly larger (10 nm) and circulate for a long time (half-life few hours in mice and up to few days in humans). There is no direct relationships between protein size and circulation time, e.g., albumin, a molecule of about the same size as plasminogen activators, circulates for much longer time (half-life of few hours). Protein conjugates can vary in size from 2–3 nm (fusion proteins) to microns (multi-molecular protein complexes and polyplexes). Proteins and protein conjugates are the least restricted to the bloodstream, which they can leave (i.e., extravasate) via diverse pathways including diffusion between endothelial cells and endocytosis via endothelium. Submicron liposomes and other carriers can extravasate in pathological tissues due to Enhanced Permeation and Retention (EPR) effect, and undergo endocytosis in endothelial cells. RBC carriers are the most restricted to the bloodstream; normally they can extravasate only in opening of reticuloendothelial system (e.g., hepatic sinuses and spleenic follicles).
| Size, nm | Shape | Half-life in blood | Diffusion in tissues | |
|---|---|---|---|---|
| RBC | 5,000–7,000 | Biconcave disc | 10–15 days | RES openings only |
| PEG-Liposomes | 50–500 | Spheres | 3–6 hours | Tumors (EPR), endocytosis |
| Polymersomes | 50–500 | Spheres | 10–20 hours | Tumors (EPR), endocytosis |
| Filomicelles | 40×20,000 | Filaments | 1–3 days | Unknown, possibly EPR |
| Polymer micelles | 20–300 | Spheres | 0.1–6 hours | Tumors (EPR), endocytosis |
| Proteins and conjugates | 5–5,000 | Irregular spheres | 10 min – 6 hours | Diffusion & endocytosis |