Introduction: A polyethylene glycol (PEG)-modified liposome is a representative drug carrier because of its long blood half-life. However, in the second time injection, PEG-liposome is rapidly removed from blood by produced... [ view full abstract ]
Introduction: A polyethylene glycol (PEG)-modified liposome is a representative drug carrier because of its long blood half-life. However, in the second time injection, PEG-liposome is rapidly removed from blood by produced antibody against PEG. Here, we focused on serum albumin to camouflage the surface of liposome to prolong its blood circulation time. Human serum albumin (HSA) is the most abundant protein in plasma (~40 g/L). Since serum albumin can avoid from removal via glomerular filtration and degradation in endocytosis, it has a long blood half-life (20 days). Here we propose modification of the liposome surface via serum albumin-binding ligands for reversible coating with HSA. As such a ligand, we selected alkyl ligand with various hydrophobicity; stearic acid (SA), octadecanedioic acid (OA), and decanoic acid (DA).
Method: Three types of ligand-modified phospholipids were synthesized. Then, liposomes containing these lipids were prepared by a hydration method (SAL, OAL, and DAL) (Fig. 1). To confirm the stability of these liposomes in physiological saline, these liposomes were incubated in DPBS containing human serum albumin (HSA) at r.t. The size of liposome was measured 20 h after the incubation. The exposure of OA to out-phase was determined from the change of dispersion stability in acidic solution.
Results and Discussion: OAL and DAL aggregated in DPBS in the absence of HSA, while SAL dispersed stably (Fig. 2). This result indicated that the less hydrophobic ligands OA and DA are exposed on the liposomal surface, resulting in aggregation via interparticle hydrophobic interaction, while the highly hydrophobic SA may be buried in liposomal bilayer, leading to stable dispersion. In the presence of HSA, OAL and DAL dispersed stably, indicating that HSA interacts with the ligand of OAL and DAL to suppress the aggregation. Interestingly, the aggregation of OAL in the absence of HSA was suppressed in acidic condition, indicating that the protonated OA is buried into bilayer like SA (Fig. 3). The unique behavior of OAL indicates that negatively charged OA at neutral condition is exposed on the liposomal surface to readily bind with HSA. The present finding will provide useful information to design an albumin-coated liposome.
Targeted drug delivery and nanocarriers , Nanomedicine for cancer diagnosis & therapy
