Temperature Sensitization of Liposomes by Use of Thermosensitive Block Copolymers Synthesized by Living Cationic Polymerization:  Effect of Copolymer Chain Length

Abstract

We prepared block copolymers of (2-ethoxy)ethoxyethyl vinyl ether (EOEOVE) and octadecyl vinyl ether (ODVE) with the number average molecular weights of 6900, 9300, and 16 700 by living cationic polymerization. The poly(EOEOVE) block acts as a temperature-sensitive moiety, and the poly(ODVE) block acts as an anchor moiety. We also investigated the effect of chain length of the copolymer poly(EOEOVE) block on the ability to sensitize liposomes. The copolymers underwent a coil-globule transition at approximately 36 degrees C in the presence of a membrane of egg yolk phosphatidylcholine (EYPC), detected using differential scanning calorimetry (DSC). Liposomes encapsulating calcein, a water-soluble fluorescent dye, were prepared from mixtures of dioleoylphosphatidylethanolamine, EYPC, and the copolymers. While the copolymer-modified liposomes released little calcein below 30 degrees C, release was enhanced above 35 degrees C, indicating that dehydrated copolymer chains destabilized the liposome membrane. In addition, copolymers with a longer poly(EOEOVE) block induced a more drastic enhancement of contents release in a narrow temperature region near the transition temperature of the poly(EOEOVE) block. As a result, the copolymer with an average molecular weight of 16 700 generated highly sensitive liposomes that produced rapid and dramatic release of the contents in response to temperature.

Phase Separation Dynamics of Aqueous Poly [(2‐ethoxy) ethoxy ethyl vinyl ether] Solutions as Explored using the Laser T‐Jump Technique Combined With Photometry

“…Thus, the fast PS component ( τ 1 ) should become faster still with increasing C , as clearly demonstrated in Figure 5 a. It should be noted here that interchain aggregation even below LCST (meaning before PS) was also discussed for a block copolymer system of poly(EOEOVE) and octadecyl vinyl ether, [ 38 ] reinforcing our deduction where intermolecular aggregates play an important role in PS.…”

Effect of polymer characteristics on structure of polymer–liposome complexes

“…Such disagreements between the thermal properties of the bilayers and the anisotropy ratios suggest that the anisotropy ratio is not a function of the bilayer properties but rather represents macroscopic properties of the vesicle, specifically, the vesicle size. This conclusion is supported by the results of Kono et al [32] who found that polymer-associated liposomes with similar vesicle sizes have almost the same membrane fluidity regardless of differences in the molecular weight and concentration of the polymers.…”

Multi-functional liposomes having temperature-triggered release and magnetic resonance imaging for tumor-specific chemotherapy

“…Copoly[EOEOVE-block-octadecyl vinylether(ODVE)] was synthesized as previously reported using 1-(ethoxy)ethyl acetate as the initiator [36]. The number average molecular weight and polydispersity index of copoly(EOEOVE-block-ODVE) were estimated to be 1.3x10 4 and 1.03, respectively, using gel permeation chromatograpy.…”

“…Because of the highly branched backbone structure with many chain terminals, the dendron moiety taking on a compact conformation can hold many Gd-chelate residues. Based on the highly temperature-responsive liposomes, which were developed recently by modification of pegylated liposomes with thermosensitive poly [2-(2-ethoxy)ethoxyethyl vinyl ether-block-octadecyl vinyl ether (EOEOVE-block-ODVE)] with a lower critical solution temperature (LCST) around 40°C [36,37], we incorporated the dendron-based lipid having many Gd-chelates into the poly(EOEOVE-block-ODVE)-modified liposomes ( Figure 1). Performances of the liposomes from the sense of visualization and tumor-chemotherapy were investigated.…”