In some cases, both mechanisms were suggested to contribute to the

transport of lipids between vesicles [18] and to the transport of lipophilic drugs from oil-in-water emulsions to cells [19] and from plasma proteins to lipid vesicles [20]. In our preceding experimental work, where we have investigated the kinetics of temoporfin transport from donor to acceptor liposomes [13], we found that above a certain concentration (corresponding to a liposome-to-liposome distance of about 200nm for our specific system) the transfer was dominated by collisions; for smaller concentrations transport through diffusion was prevalent. The objective of the present work is to introduce and discuss a detailed kinetic model for the release properties of poorly water-soluble Inhibitors,research,lifescience,medical drug molecules from liposomal nanocarriers. Despite

a large number of experimental studies about the kinetics of lipid and drug transfer between liposomes and other nanocarriers, there is FK228 chemical structure little theoretical work available that addresses the nature of the transfer kinetics. Our theoretical formalism is based on Inhibitors,research,lifescience,medical a detailed distribution function of drug molecules among the individual liposomes. Kinetic rate equations for that distribution function account for Inhibitors,research,lifescience,medical two transport mechanisms: collisions between liposomes and drug diffusion through the aqueous phase. We specify a set of conditions at which our microscopic model produces an apparent first-order kinetics Inhibitors,research,lifescience,medical with simple exponential behavior, as used in previous work [14, 19]. We point out that our kinetic model can be applied to any kind of small

mobile pharmaceutical nanocarrier, including liposomes, micelles [21], colloids [22], and nanoparticles [23]. In the second part of our work, we discuss conditions that lead to deviations from simple exponential behavior. First, for the diffusion mechanism, high drug loading tends to increase the transfer rate. The kinetics remains exponential only if donor and acceptor liposomes are chemically similar. Second, the presence of attractive interactions between drug molecules within the liposomes (which can result in the formation of aggregates [24]) is expected Inhibitors,research,lifescience,medical to slow down the transfer kinetics. We note that not much molecular detail is presently known about how poorly water-soluble drug molecules inside a lipid bilayer interact. However, modeling studies Terminal deoxynucleotidyl transferase of rigid membrane-embedded inclusions such as transmembrane proteins or peptides suggest a general tendency of the host membrane to mediate attractive interactions between inclusions that may lead to the formation of aggregates [25]. These attractive interactions may be driven by elastic deformations of the host membrane [26], by depletion of the flexible lipid chains from the region in between rigid inclusions [27], and by fluctuations via the Casimir effect [28]. Our analysis for the collision mechanism suggests that aggregate formation can give rise to sigmoidal behavior of the transfer kinetics.