Natural amphiphiles provides important self-assembling molecules for the preparation of nanostructures for environmental friendly and biomedical applications in nanotechnology. They can be used directly in the applications or can be modified to introduce additional functionalities and self-assembly features which can result in improved performances. Bile salts (BSs) are anionic natural steroidal surfactants obtained as products of the major route of the cholesterol methabolism. They have appealing amphiphilic features for the preparation of encapsulators and drug carriers and in the synthesis of inorganic nanoparticles. This project is aimed at exploring self-assembly and applications of BS and BS derivatives (BSD) obtained by performing modification of BS. The modifications are properly addressed to improve their efficiency in the applications. The project will be focused in particular on the investigation of: i) mixtures of BS and BSD with other natural amphiphiles like lecithin and with block copolymers (BC), to analyze the potential of BC as BS sequestrants in the treatment of BS malabsorption and hypercholesterolemia and the suitability of BS- and BSD-BC-lecithin mixed aggregates as drug carriers; ii) BSD containing polymerizable functions for the preparation of BSD based polymeric encapsulators; iii) the employment of BSD supramolecular nanotubes in the fabrication of supracolloidal superstructures.
BS and BSD in nanomedicine.
As previously observed for BSs [14], the BSDs used in this part of the project will be easily included in the liposome membrane to form transferosomes. Hence, thanks to the presence of the mannose [10,12] and RGD moieties [15], the BSDs will confer to transferosomes the targeting ability in addition to the already known elasticity.
Concerning BS- and BSD-Block Copolymer systems, it is anticipated that mixed aggregates will be formed in the oppositely charged BS and BSD-BC mixtures composed by an electroneutral interior including the charged blocks and bile salt molecules and a corona formed by the neutral block. Amphiphilic thermoresponsive block copolymers will form aggregates able to open up by heating and to release the interior, thus providing an interesting carrier for the transportation and the controlled release of drugs. The use of BSs and BSDs is expected to improve the biocompatibility of the carriers thank to their biological origin.
Regarding BS- and BSD-BC-lecithin systems, the formation of mixed aggregates can be easily anticipate, whose characterization will provide important information on the potential of these formulations for the preparation of BS- and BSD-BC-lecithin based drug carriers. It is known that BSs are also used as co-agents in formulations for dispersion of drugs since they improve the drug penetration and absorption. Indeed, mixed micelles and vesicles containing bile salts and lecithin were employed as carriers for delivering drugs across the intestinal walls. BSDs would preserve this permeation enhancer ability, hence both BS and BSD should be able to promote the permeation of the drugs, whenever used in the formulation of drug carriers.
BSD self-assembly and fabrication of polymeric tubular encapsulators.
BS and BSD have an amphiphilic structure different from the typical head-tail one of conventional surfactants. For this reason, they show unconventional self-assembly behaviors as well as solubilization and permeation abilities. In particular, their steroidal nature and the presence of polar hydroxyl groups beside their main polar carboxylic head, allow them to form ordered sometimes quasi-crystalline supramolecular structures stabilized by intermolecular hydrogen. Proper modifications of BS molecules afford the preparation of BSD which self-assemble in tubular structures with different sizes that can be employed in the above mentioned fields of supracolloid framework or encapsulation. With this respect, BS with styrene or divinylbenzene containing residues are expected to provide supramolecular tubules that could afford polymeric nanotube via styrene and divinylbenzene polymerization, thereby providing stable tubular encapsulators of different materials.
BSD tubules in the formation of supracolloidal frameworks.
It as been reported that spherical particles of silica can be included in tubes of sodium dodecyl sulfate and cyclodextrin, forming chains of particles with different regular patterns depending on the particle sizes. We believe that similar results can be obtained by using microgels and BSD tubes. 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. The thermoresponsiveness of the microgels and the catanionic character of the tubes will allow a control over the tube-particle interaction which was not possible in the previous study.