Ž . Biochimica et Biophysica Acta 1345 1997 43–55 Serum–liposome interaction is an oxygen-dependent process Merce Foradada a , Anna Manzano b , Teresa Roig c , Joan Estelrich a , Jordi Bermudez c, ) ` ´ a Unitat de Fisicoquımica, Facultat de Farmacia, UniÕersitat de Barcelona, AÕda. Joan XXIII s r n, E-08028 Barcelona, Spain ´ ` b Unitat de Bioquımica, Campus de BellÕitge UniÕersitat de Barcelona, L’Hospitalet de Llobregat, E-08907 Barcelona, Spain ´ c Unitat de Biofısica, Campus de BellÕitge UniÕersitat de Barcelona, L’Hospitalet de Llobregat, E-08907 Barcelona, Spain ´ Received 24 July 1996; revised 14 October 1996; accepted 18 October 1996 Abstract Measurements of heat dissipation, oxygen concentration and average vesicle size were correlated to study the effect of serum components on different types of liposome. The results indicate that the interaction between serum components and liposomes is exothermic and oxygen dependent, and leads to disruption of vesicles. The dependence of this effect on serum concentration, vesicle surface charge and type of liposome was also evaluated. Serum components did not produce any effect on conventional liposomes in the absence of oxygen. Moreover, in hypoxic conditions the serum–liposome interaction was delayed. Both results suggest that this interaction is an oxygen-dependent event. Finally, we confirmed that sterically stabilised liposomes remain unalterated in the presence of serum. Keywords: Liposome; Serum; Serum–liposome interaction; Microcalorimetry 1. Introduction Liposomes have been investigated since 1970 as a system for the delivery of drugs. Because of their structural versatility in terms of size, composition, surface charge, bilayer fluidity and ability to incorpo- rate almost any drug regardless of solubility, lipo- somes have the potential to be tailored in a variety of Abbreviations: DRV, dehydration–rehydration vesicles; DSPC, distearoylphosphatidylcholine; DSPE, distearoylphos- phatidylethanolamine; FCS, foetal calf serum; HDL, high density lipoproteins; MLV, multilamellar liposomes; MPS, mononuclear phagocytic system; PA, phosphatidic acid; PC, phosphatidyl- choline; PCS, photon correlation spectroscopy; STE, steary- lamine. ) Corresponding author. Fax: q34 34.02.42.13; E-mail: bermudez@bellvitge.bvg.ub.es ways to ensure the production of optimal formula- tions for clinical use. However, the potential use of liposomes as deliv- ery systems by intravenous injection is limited by their low stability in the bloodstream and by their removal by cells of the mononuclear phagocytic sys- Ž . wx tem MPS , particularly in liver and spleen 1 . Sev- eral proteins in plasma may bind to phospholipids from damaged cells, or from bacteria and other for- eign material such as liposomes, acting as natural opsonines and increasing macrophage phagocytosis w x 2–8 . In addition, plasma high density lipoproteins Ž . HDL destabilise liposomes, probably through re- wx moval of phospholipid from the bilayer 9 , which w x produces leakage of their contents 2,10,11 and w x clearance from the biological milieu 12 . These lipo- somes with short half-lives in circulation are now called ‘conventional’ or C-liposomes, and their thera- 0005-2760r97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0005-2760 96 00157-9