Photoresponsive liposomal nanohybrid cerasomes. A.R Photoresponsive liposomal nanohybrid cerasomes. Xiaolong Liang,a Xiuli Yue,a Zhifei Dai*a and Jun-ichi Kikuchi*b Received 5th January 2011, Accepted 24th February 2011 a) Nanomedicine and Biosensor Laboratory, Harbin Institute of Technology, China. b) Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Japan.

Introduction. Nanomaterials as for controlled release . Mesoporous silica nanoparticle . But have high rigidity & mass density as Well as low biocompatibility. Liposomes function as targeted release. Insufficient morphological stability. Incorporation of azobenzene.

The cerasome is a lipid bilayer vesicle having silicate frameworks on its surface. Molecular-sized bubbles filled with C6-ceramide, which is used as an anti-cancer agent. Ceramide is a lipid molecule naturally present in the cell’s plasma membrane and controls cell functions, including cell aging, or senescence. A unique point of the cerasome is that it is derived from the organoalkoxysilane derivative, having both an organic and an inorganic part connected to each other in the molecule. Cerasomes Functions of ceramides Purely structural elements ?? This is now known to be not completely true. Ceramide can actually act as a signaling molecule. It also include regulating the differentiation, proliferation, programmed cell death (PCD), and apoptosis (Type I PCD) of cells.

Nile blue (or Nile blue A) is a stain used in biochemistry Nile blue (or Nile blue A) is a stain used in biochemistry. It can be used with live or fixed cells and imparts a blue colour to cell nuclei. Nile blue Nile red (also known as Nile blue oxazone) is a lipophilic stain. It is produced by boiling a solution of Nile blue with H2SO4 . Nile red stains intracellular lipid droplets red. It has a strong yellow-gold emission when in a lipid-rich environment. It excites at 485 nm and emits at 525 nm. Nile red

The sol-gel process, is a wet-chemical technique widely used primarily for the fabrication of materials starting from a chemical solution (or sol) that acts as the precursor for an integrated network (or gel) of either discrete particles or network polymers. The atomic layer of the polyorganosiloxane surface gives higher morphological stability. Azobenzene moiety can use to control the photoactivated release of guest molecules .

Photoresponsive Cerasomes (PRCs). Bangham Method. Upon ultrasonication, the liposomal bilayer formed and self-rigidified via in situ sol–gel processes (Si–OCH2CH3+H2O - Si–OH + CH3CH2OH followed by 2Si–OH - Si–O–Si + H2O) on the surface. It is a novel organic/inorganic hybrid having a precise nano structure. The thickness of both the organic and inorganic layer attributed to the molecular structure and the size of the vesicle is controllable by conventional methodologies. The formation of siloxane bond. Stretching bands assigned to the Si–O–Si and Si–OH groups were observed. PRCs had a silica-like surface with siloxane frameworks & a high degree of polymerization.

Average hydrodynamic diameters (Dh) and polydispersity index (PDI). Dh = 105.2 ± 15.1 nm PDI = 0.19 ±0.05 nm Dynamic light scattering (DLS) measurements. TEM SEM Diameter ranging from 60-150 nm

Stability of PRCs. Surfactant dissolution experiments.. Dh of conventional liposome from distearoyl phosphatidylcholine was drastically decreased, but that of the PRCs was almost unchanged. PRCs exhibited remarkable morphological resistance toward both acidic and alkaline conditions, but it will destroys conventional liposomes.

Absorption Spectra of PRCs. Solvent- CHCl3 Decrease in 362 nm & Increase in 450 nm UV/vis absorption spectra of AZOSIL lipid in CHCl3

AZOSIL lipid in CHCl3 aqueous PRC Rate and ratio of trans-to-cis isomerization is slower and lower in cerasomes than in CHCl3, which further confirms the formation of bilayer membrane. It also shows that 33.40% of trans PRC isomerized to cis to reach a PSS after 19 min irradiation in contrast to 46.87% in CHCl3 . It is because closely-packed bilayer membranes restrict isomerization of the azobenzene units. This indicating that the azobenzene unit does not decompose or induce undesirable side reactions. The DLS analysis showed that the Dh value of the vesicles is similar to that of the vesicle before irradiation with UV light

Capability of PRCs to release molecules. Change in fluorescence of Nile Red: (a) PRC upon UV light irradiation, (b) PRC in the dark, (c) cerasomes without azobenzene unit upon UV light irradiation. Nile Red loaded PRC dispersions: (d) before, (e) during and (f) after UV light irradiation. The release of Nile Red molecules from the membrane of the vesicle into the aqueous phase was monitored by fluorescence spectroscopy. Upon UV the cis-azobenzene enhanced repulsive interaction between the geometrically distorted amphiphiles, which would lead to increased permeability of membrane. The azobenzene units act as molecular impellers, so the encapsulated molecules are released from the vesicle into the aqueous media, resulting in a decreased fluorescence of Nile Red.

After UV light irradiation for 20 min, about 48 After UV light irradiation for 20 min, about 48.2% of Nile Red was released from PRC. For PRC, stretching bands assigned to the Si-O-Si and Si-OH groups were observed around 1100 and 950 cm-1, respectively which can’t be seen for photoinduced precipitate and Nile Red. Organoalkoxysilylated lipid without an azobenzene unit. Further confirms that the photoisomerization of the azobenzene moiety, behave as a ‘‘valve’’ with an ‘‘on–off’’ function under specific stimuli in a photoresponsive release system.

Advantages. The atomic layer of the polyorganosiloxane surface imparts higher morphological stability to the PRC than conventional liposomes. The liposomal bilayer structure leads to lower rigidity and density compared to silica nanoparticles. The introduction of a photoisomerizable azobenzene moiety would provide a tool to control the photoactivated release of guest molecules. The synthesis strategy based on multivalent pentaerythritol can be readily applied to synthesize other functional lipids.

Conclusion. For the first time ,an innovative and general strategy was presented, as a proof-of–concept, for preparing a new type of highly stable PRC from a molecularly designed AZOSIL lipid. They showed the capability of using PRCs to optically control the release of loaded guest molecules from the membrane of the vesicle. thank you