Polymersomes from Hybrids -Polypeptides for Drug Delivery Applications.

Recently, the explosion of progress of materials at the nanoscale level has paved the way for a new category of healthcare technologies termed nanomedicine. Nanomedicine involves materials at the nanometer level for products that can improve the currently used technologies for biomedical applications. While traditional therapeutics have allowed for limited control of their distribution in the body and clearing times, engineering at the nanoscale level has allowed for significant advances in biocompatibility, biodistribution, and pharmacokinetics. Among all materials, polymers have dominated the nanomedicine world, due to their ability to manipulate their properties by combining different materials in a wide variety of macromolecular architectures. The development of novel polymeric materials is guided by the goal of improving patient survival and quality of life by increasing the bioavailability of drug to the site of disease, targeting delivery to the pathological tissues, increasing drug solubility, and minimizing systemic side effects. Polymersomes (vesicles) are the only type of polymeric nanocarriers that can physically encapsulate at the same nanoparticle hydrophilic drugs in their aqueous interior and/or hydrophobic agents within their lamellar membranes. Polymersomes have been shown to possess superior biomaterial properties compared to liposomes, including greater stability and storage capabilities, as well as prolonged circulation time.

Synthesis and Characterization of the Novel Nε-9-Fluorenylmethoxycarbonyl-l-Lysine N-Carboxy Anhydride. Synthesis of Well-Defined Linear and Branched Polypeptides.

The synthesis of well-defined polypeptides exhibiting complex macromolecular architectures requires the use of monomers that can be orthogonally deprotected, containing primary amines that will be used as the initiator for the Ring Opening Polymerization (ROP) of N-carboxy anhydrides. The synthesis and characterization of the novel monomer Nε-9-Fluorenylmethoxycarbonyl-l-Lysine N-carboxy anhydride (Nε-Fmoc-l-Lysine NCA), as well as the novel linear Poly(Nε-Fmoc-l-Lys)n homopolypeptide and Poly(l-Lysine)78-block-[Poly(l-Lysine)10-graft-Poly(l-Histidine)15] block-graft copolypeptide, are presented. The synthesis of the graft copolypeptide was conducted via ROP of the Nε-Boc-l-Lysine NCA while using n-hexylamine as the initiator, followed by the polymerization of Nε-Fmoc-l-Lysine NCA. The last block was selectively deprotected under basic conditions, and the resulting ε-amines were used as the initiating species for the ROP of Nim-Trityl-l-Histidine NCA. Finally, the Boc- and Trt- groups were deprotected by TFA. High Vacuum Techniques were applied to achieve the conditions that are required for the synthesis of well-defined polypeptides. The molecular characterization indicated that the polypeptides exhibited high degree of molecular and compositional homogeneity. Finally, Dynamic Light Scattering, ζ-potential, and Circular Dichroism measurements were used in order to investigate the ability of the polypeptide to self-assemble in different conditions. This monomer opens avenues for the synthesis of polypeptides with complex macromolecular architectures that can define the aggregation behavior, and, therefore, can lead to the synthesis of "smart" stimuli-responsive nanocarriers for controlled drug delivery applications.