Young's moduli of surface-bound liposomes by atomic force microscopy force measurements.

Mechanical properties of layers of intact liposomes attached by specific interactions on solid surfaces were studied by atomic force microscopy (AFM) force measurements. Force-distance measurements using colloidal probe tips were obtained over liposome layers and used to calculate Young's moduli by using the Hertz contact theory. A classical Hertz model and a modified Hertz one have been used to extract Young's moduli from AFM force curves. The modified model, proposed by Dimitriadis, is correcting for the finite sample thickness since Hertz's classical model is assuming that the sample is infinitely thick. Values for Young's moduli of 40 and 8 kPa have been obtained using the Hertz model for one and three layers of intact liposomes, respectively. Young's moduli of approximately 3 kPa have been obtained using the corrected Hertz model for both one and three layers of surface-bound liposomes. Compression work performed by the colloidal probe to compress these liposome layers has also been calculated.

Liposome layers characterized by quartz crystal microbalance measurements and multirelease delivery.

Intact liposomes have been immobilized onto solid surfaces by a NeutrAvidin-biotin link. The construction of these layers has been followed up by X-ray photoelectron spectroscopy (XPS) and quartz crystal microbalance (QCM) measurements with energy dissipation monitoring. Also, the simultaneous release of two fluorescent probes from these liposome layers has been investigated with the aim to validate this method in multirelease delivery systems. XPS showed the successful immobilization of the different layers. XPS results also point out the importance of the deactivation method used to reveal the presence of the specific NeutrAvidin-biotin attachment. QCM measurements allowed the buildup of the different layers to be followed in real time and in situ and suggest that biotinylated liposomes stay intact upon surface attachment on NeutrAvidin-covered surfaces and had viscoelastic behavior. QCM experiments also demonstrated that surface-immobilized liposomes were able to resist irreversible adsorption from fetal bovine serum. Release kinetic profiles were studied by monitoring the release of two different fluorescent probes, namely, carboxyfluorescein and levofloxacin, from these liposome layers. These studies showed that it was possible to modulate to some extent the release rates of the two molecules by using different configurations of liposome layers.

Fabrication and characterization of contact lenses bearing surface-immobilized layers of intact liposomes.

Intact liposomes were immobilized onto soft contact lenses. In the first step, polyethylenimine was covalently bounded onto the hydroxyl groups available on the surface of a commercial contact lens (Hioxifilcon B). Then, NHS-PEG-biotin molecules were bounded onto the surface amine groups by carbodiimide chemistry. NeutrAvidin were bounded onto the PEG-biotin layer. Liposomes containing PEG-biotinylated lipids were docked onto the surface-immobilized NeutrAvidin. Consecutive addition of further NeutrAvidin and liposome layers enabled fabrication of multilayers. Multilayers of liposomes were also produced by exposing contact lenses coated with NeutrAvidin to liposome aggregates produced by the addition of free biotin in solution. XPS revealed the immobilization of the different layers. By blocking with excess biotin surface-immobilized NeutrAvidin on contact lenses bearing PEG-biotin layers produced under cloud point conditions, ELISA showed that the docking of NeutrAvidin was dependent on biotin-NeutrAvidin affinity binding, with little evidence for nonspecific physisorption; however, it was not possible to differentiate specific versus nonspecific binding of NeutrAvidin attached onto PEG-biotin layers grafted without cloud point conditions. AFM imaging revealed liposome sizes of 106 and 155 nm for layers of liposomes produced (i) by the consecutive addition of further NeutrAvidin and liposomes and (ii) by the exposure of NeutrAvidin-coated contact lenses to liposome aggregates, respectively. The release kinetics of a fluorescent dye demonstrated that intact liposomes had been immobilized onto contact lens surfaces. The stability of surface-immobilized liposomes onto contact lens surfaces showed temperature dependence. Surface-bound liposomes can be stored up to 1 month at 4 degrees C with little release of their content.

Drug delivery systems using immobilized intact liposomes: a comparative and critical review.

Liposomes sustain considerable interest to develop ways to fabricate drug delivery systems that would provide a good release without inducing any systemic reactions into the host. However, in many cases, liposomes injected into the blood stream are rapidly cleared from the system and only a fraction reaches the target site even when poly(ethylene glycol) (PEG)-coated liposomes are used. Composite drug delivery systems with liposomes i.e., liposomes linked to other substrates can be good candidates for certain type of drug release to achieve a localised treatment. This paper reviews the fundamental phenomena of the interactions between liposomes and solid substrates. Then, we address various techniques that have been used to immobilize intact liposomes onto and into different substrates. Finally, properties of liposomes used as drug delivery systems are briefly reviewed.