Self-assembly of amphiphiles is a common method in the fabrication of nanostructures for nanoscience by a bottom up approach. Natural amphiphiles are particularly interesting as they are environmental friendly and employable in biomedical fields. Starting from them, derivatives with additional functionalities and self-assembly features can be synthesized, which can result in improved performances in the applications. Bile salts (BS) are anionic natural steroidal surfactants deeply involved in various biological processes and with appealing amphiphilic features for various applications. This project is aimed at studying the self-assembly of BS and BS derivatives (BSD) obtained by chemical modification of BS, and at exploring their effects and potential in different nanotechnologies and fundamental researches. A study of association behavior in BS- and BSD-Block copolymer(BC)-lecithin mixtures is proposed to investigate: i) the effect of BS on BC micelles and liposomes usually employed in drug delivery; ii) the potential of BC as BS sequestrants in the treatment of BS malabsorption and hypercholesterolemia; iii) the potential of BS- and BSD-BC-lecithin mixed aggregates as drug carriers. The application of BS and BSD in the alignment of metal nanoparticles and synthesis of nanowire and in the fabrication of supracolloidal framework will be also explored.
BSD self-assembly
The amphiphilic structure of BS is different from that of the conventional surfactant, generally formed by hydrophilic head and a flexible hydrophobic chain. In particular, due to their steroidal skeleton and the presence of polar hydroxyl groups, in addition to the main polar carboxylic head, BS are able to form ordered, sometimes quasi-crystalline supramolecular structures, stabilized by intermolecular hydrogen bonds. BSD preserve these properties and have additional and novel suitable features for preparation of self-assembled nanomaterials. For example, BSD forming stimuli-responsive[10¿12,21] or catanionic nanotubes have been recently prepared for supracolloid framework or nanowire preparation. The AD containing BSD catanionic mixtures and the AZ containing derivative are expected to provide new catanionic structures and photo-responsive nanoaggregates, respectively.
BSD in the alignment of nanoparticles and synthesis of nanowires
The BSD tubular structures have several advantages in the proposed preparation of nanowires:
- BSD based nanotubes can be prepared with different sizes [22], thus allowing for inclusion of seeds of different size and for the preparation of nanorods or nanowires with different thicknesses.
- BSD stimuli-responsive tubules will be used whose formation can be triggered by controlling convenient parameters, such as temperature and pH [10¿12]. In a solution containing the surfactant with complexed metal ions and metal seeds, this control should result in controlled inclusion or release of seeds and wires in or from the channels.
- the use of BSD based catanionic tubules [13], allow us to regulate the formation of the nanohybrid, via the electrostatically driven upload of the nanoparticles, by properly controlling the catanionic mixture composition.
Therefore BSD nanotubes are particularly versatile and suitable compared to conventional surfactant nanotubes in the preparation of the nanotube-nanoparticle nanohybrids. Systems containing a single BSD and mixtures of BSD will be used. Effects of different types and mixture compositions of BSD and of the concentration of seeds will be studied. This approach will allow us to find a proper hybrid structure of seed-including tubules and to unravel the mechanism of their formation. Therefore proper condition for the formation of optimal tubule-forming hybrids and nanowire meshes will be achieved.
BS- and BSD-BC-lecithin mixtures for nanomedicine
A. BSD-lecithin systems. As previously observed for BS [3], the BSD will be easily included in the liposome membrane to form transferosomes. The presence of mannose [14,23,24] and RGD moieties in the BSD will confer to transferosomes the targeting ability in addition to the already known elasticity.
B. BS- and BSD-Block Copolymer systems. It is anticipated that oppositely charged BS and BSD-BC mixtures will form mixed aggregates with an electroneutral interior including the charged blocks and bile salt molecules and a corona formed by the neutral block. These aggregates will provide a potential carrier for the transportation and the controlled release of drugs, especially in the case of amphiphilic thermoresponsive BC. The use of BS and BSD has interesting advantages:
i) due to their biological nature BS are expected to improve the biocompatibility of the carriers;
ii) a multi- and/or complex stimuli responsive behavior is expected in mixed aggregates formed by thermoresponsive BC and pH- or thermo-responsive BSD due to the sum of stimuli sensitivities of BC and BSD.
Thermally stable complexes could be formed by the non-thermoresponsive PEGn-PAMPTMA(+)m. Hence it could be a good candidate as a new BS sequestrant.
C. BS- and BSD-BC-lecithin systems. These three solute systems has not been explored so far. The formation of mixed aggregates can be anticipated. The study will provide information on the effect of bile on lecithin and BC based drug carriers when entering the enterohepatic circulation and on their potential as drug carriers.
It is known that BS are used as co-agents in formulations for dispersion of drugs as they improve the drug penetration and absorption. BSD would preserve this ability when used in the formulation of drug carriers.
BSD tubules for supracolloidal frameworks
It was reported that tubes of sodium dodecyl sulfate and cyclodextrin can include spherical particles of silica forming particle chains with regular particle size dependent patterns [19]. In our case, due to the size of the microgels, similar or larger than the tube diameters, the interactions is expected to occur on the external surface of the tubes. Ordered structures are expected to form. The thermoresponsiveness of the microgels and the catanionic character of the tubes will allow for a control over the tube-particle interaction, not possible in the previous studies.
References are reported in the section -Eventuali altri partner esterni e ruolo nel progetto-