Controlling the Release from Supported Vesicle Layers on LbL Films

INTRODUCTION: Liposomes are among the most used delivery vesicles. However, their adsorption on solid surfaces usually results in their spontaneous reorganization and formation of a supported lipid bilayer [1,2]. This reorganization compromises the compartmentalization and change the uptake and release of bioactive agents. We hypothesize that soft layer-by-layer (LbL) supports would minimize colloidal instability of liposomes upon adsorption and promote supported vesicular layers (SVL).

METHODS: Gold-coated quartz crystals were modified with 3 bilayers of cationic poly-L-lysine (PLL) and anionic hyaluronic acid (HA). A top layer of cationic liposomes loaded with Nile Red (d=120 nm, ζ-potential=10 mV) was added, followed by 2 HA/PLL bilayers. The assembly was monitored by quartz crystal microbalance with dissipation (QCM-D). The encapsulation efficiency (EE) and release to NaCl 0.15 M were quantified by fluorescence spectroscopy.

RESULTS & DISCUSSION: Our QCM-D data demonstrated that indeed a phospholipid bilayer is formed upon adsorption of the liposomes on bare gold crystals. When the deposition was carried out on soft LbL substrates instead, we observed adsorption of intact spherical liposomes. We determined an average EE of 5.4 ng/cm² for these constructs and 12% release after 1 h. Further coating of the constructed SVL with HA/PLL bilayers did not compromise their stability and increased the diffusion barrier: only 4% (three fold less) of Nile Red were released from the SVL coated with 2 HA/PLL bilayers. This result showcases that the release can be controlled by additional top layers but also the protective efficiency of this coating as compared to free liposomes in aqueous suspension (~29%).

CONCLUSIONS: SVLs show promise for compartmentalized 2D films where small amounts of biomolecules are encapsulated for diagnostic and therapy. Liposomes will allow expanding these systems further to bioactive hydrophilic species.

ACKNOWLEDGEMENTS: Portuguese FCT (PTDC/BTM-MAT/28327/2017, IF/00032/2013, SFRH/BPD/95446/2013), FSE and POCH, EU H2020 ELASTISLET (NMP-2014-646075), Spanish AEI, ERDF (project MAT2016-80266-R).

REFERENCES
[1] Kumar A. et al. Journal of Colloid and Interface Science 2016; 473:152-61
[2] Gillissen J. J. J. et al. Langmuir 2018; 34(1):503-111