Ivo Panzani

Erythrocyte engineering for drug delivery and targeting.

A new procedure for the encapsulation of non‐diffusible drugs into human erythrocytes was developed. With as little as 50 ml of blood and by using a new apparatus, it was possible to encapsulate a variety of biologically active compounds into erythrocytes in 2 h at room temperature and under blood‐banking conditions. The process, which is based on two sequential hypotonic dilutions of washed red cells followed by concentration with a haemofilter and resealing of red cells, allows a 35–50% cell recovery and approx. 30% encapsulation of added drugs. The resulting processed erythrocytes have a normal survival in vivo and can be modified further, with the same apparatus, to increase their recognition by tissue macrophages to perform as a drug‐targeting system. The new equipment designed and built for this procedure was named ‘Red Cell Loader’.

Erythrocyte‐mediated delivery of dexamethasone in patients with chronic obstructive pulmonary disease

Human erythrocytes from ten patients with chronic obstructive pulmonary disease (COPD) were loaded with increasing amounts of dexamethasone 21‐phosphate and were re‐infused into the original donors. Drug‐loaded erythrocytes acted as circulating bioreactors, converting the non‐diffusible dexamethasone 21‐phosphate into the diffusible dexamethasone. Pharmacokinetic analyses on these patients showed that a single administration of drug‐loaded erythrocytes was able to maintain detectable dexamethasone concentrations in blood for up to seven days. This continuous release of dexamethasone was paralleled by the suspension of β2‐agonist and oral corticosteroid treatments by all of the patients. Thus dexamethasone 21‐phosphate‐loaded erythrocytes are safe carriers for corticosteroid analogues and are a useful alternative to frequent oral or inhaled drugs in elderly patients with COPD.