SYNOPSISHydrophilic nanoparticulate carriers have important potential applications for the administration of therapeutic molecules. The recently developed hydrophobic-hydrophilic carriers require the use of organic solvents for their preparation and have a limited protein-loading capacity. To address these limitations a new approach for the preparation of nanoparticles made solely of hydrophilic polymers is presented. The preparation technique, based on an ionic gelation process, is extremely mild and involves the mixture of two aqueous phases at room temperature. One phase contains the polysaccharide chitosan (CS) and a diblock copolymer of ethylene oxide and propylene oxide (PEO-PPO) and, the other, contains the polyanion sodium tripolyphosphate (TPP). Size (200-1000 nm) and zeta potential (between /20 mV and /60 mV) of nanoparticles can be conveniently modulated by varying the ratio CS/PEO-PPO. Furthermore, using bovine serum albumin (BSA) as a model protein it was shown that these new nanoparticles have a great protein loading capacity (entrapment efficiency up to 80% of the protein) and provide a continuous release of the entrapped protein for up to 1 week.
CS and CS/PEO-PPO nanoparticles prepared by a very mild ionic crosslinking technique are novel and suitable systems for the entrapment and controlled release of proteins and vaccines.
The controlled self-assembly of complex molecules into well defined hierarchical structures is a promising route for fabricating nanostructures. These nanoscale structures can be realized by naturally occurring proteins such as tobacco mosaic virus, capsid proteins, tubulin, actin, etc. Here, we report a simple alternative method based on self-assembling nanotubes formed by a synthetic therapeutic octapeptide, Lanreotide in water. We used a multidisciplinary approach involving optical and electron microscopies, vibrational spectroscopies, and small and wide angle x-ray scattering to elucidate the hierarchy of structures exhibited by this system. The results revealed the hexagonal packing of nanotubes, and high degree of monodispersity in the tube diameter (244 Å) and wall thickness (Ϸ18 Å). Moreover, the diameter is tunable by suitable modifications in the molecular structure. The self-assembly of the nanotubes occurs through the association of -sheets driven by amphiphilicity and a systematic aromatic͞aliphatic side chain segregation. This original and simple system is a unique example for the study of complex self-assembling processes generated by de novo molecules or amyloid peptides. T he ability of simple molecules to spontaneously organize into well defined nanostructures is of fundamental importance and has wide ranging applications in biotechnology and materials sciences (1). In fact, characteristic lengths Ͻ100 nm are not easily accessible at present by lithographic techniques, but can be realized with biological self-assemblies such as tobacco mosaic virus, capsid proteins (2), tubulin (3), or actin (4, 5). These proteins under appropriate conditions possess the unique capability to form long filaments with a well defined diameter. However, the fabrication cost often restricts their potential interest in practical applications. Therefore, a simple alternative route has been emerged based on de novo molecules that self-organize in a programmed way (6-11). The design of such biomimetic systems requires the understanding of the relationship between the molecular structure and the self-assembly process of the nanostructures. This inspiration from natural fibers is difficult to implement when the building blocks themselves are complex, as in the case of proteins. Up to now, no simple synthetic molecule was able to self-assemble into hollow nanotubes with well defined characteristic length in the range of 20-30 nm.Lanreotide is an octapeptide synthesized as a growth hormone inhibitor. Lanreotide forms hydrogels (Autogel), which are already used in acromegaly treatment as s.c. long-acting implants (12). Here we report the molecular and supramolecular organization of self-assembling nanotubes formed by Lanreotide in water (10% wt͞wt, acetate salt). We chose a multidisciplinary approach, by combining polarized light microscopy, electron microscopy, vibrational spectroscopies, small and wide angle x-ray scattering (SAXS and WAXS, respectively) to elucidate the hierarchical structures formed by this system. The ...
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