Study of pH-sensitive copolymer/phospholipid complexes using the langmuir balance technique: effect of anchoring sequence and copolymer molecular weight.

The behavior of three copolymers of N-isopropylacrylamide (NIPAM), methacrylic acid (MAA), and hydrophobic moiety was studied at phospholipid monolayer/subphase interfaces. The hydrophobic moieties, N-terminal dioctadecylamine (DODA) and random octadecylacrylate (ODA), were used as anchoring groups. The interactions between a 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC) monolayer and the copolymers were studied using the Langmuir balance technique. The effect of subphase pH, distribution of anchors along the copolymer chain, and copolymer molecular weight on the nature of the interactions between the copolymer chains and the DSPC monolayer were investigated. A first-order kinetics model was used to analyze the copolymers adsorption at the DSPC monolayer/subphase interface and allowed the interaction area between the copolymer chains and the DSPC monolayer, A(x), to be determined. The interaction area appears to depend on the subphase pH and the copolymer molecular weight. On decreasing pH, the interaction area of high molecular weight copolymers increases significantly; this is consistent with the copolymer chain phase transition from an extended coil to a collapsed globule while pH is lowered. In the latter conformation, strong hydrophobic attractive interactions between the copolymer chains and the hydrophobic part of the DSPC monolayer favor the copolymer intercalation, which could eventually provoke the phospholipidic layer destabilization or rupture.

Study of molecular interactions between a phospholipidic layer and a pH-sensitive polymer using the Langmuir balance technique.

Molecular interactions between a terminally alkylated pH-sensitive N-isopropylacrylamide copolymer DODA-poly(NIPAM-co-MAA) and a monolayer of distearoylphosphatidylcholine (DSPC) at the air/water interface are investigated using the Langmuir balance technique. The compression isotherms ofthe copolymer monolayer at the air-water interface confirm that the copolymer undergoes a structural transition with a change in pH ranging from an extended coil state at neutral pH to a collapsed globular state at a pH corresponding to the pH of the polymer phase transition. Adsorption kinetics of DODA-poly(NIPAM-co-MAA) in the DSPC monolayer is analyzed using a first-order kinetics model allowing an effective interaction area Ax between DSPC and DODA-poly(NIPAM-co-MAA) molecules to be evaluated. The results clearly indicate that the interaction area increases with a decrease in pH. The results also suggest that the penetration of the DODA-poly(NIPAM-co-MAA) within the phospholipid monolayer is enhanced by a decrease in pH which causes a change in the copolymer structure and an increase in specific attractive interactions between the copolymer and the phospholipid. Therefore, the copolymer can trigger the destabilization or rupture of the phospholipidic layer through a simple variation in its structure associated with a variation in molecular interactions when coupled or inserted within the membrane. This study greatly supports the prospects of the copolymer-functionalized liposomes as stable and tunable carrier systems for in vivo applications in drug delivery.