Highly Branched Polymers Based on Poly(amino acid)s for Biomedical Application

Abstract

Polymers consisting of amino acid building blocks continue to receive consideration for biomedical applications. Since poly(amino acid)s are built from natural amino acids, the same building blocks proteins are made of, they are biocompatible, biodegradable and their degradation products are metabolizable. Some amino acids display a unique asymmetrical AB2 structure, which facilitates their ability to form branched structures. This review compares the three forms of highly branched polymeric structures: structurally highly organized dendrimers, dendrigrafts and the less organized, but readily synthesizable hyperbranched polymers. Their syntheses are reviewed and compared, methods of synthesis modulations are considered and variations on their traditional syntheses are shown. The potential use of highly branched polymers in the realm of biomedical applications is discussed, specifically their applications as delivery vehicles for genes and drugs and their use as antiviral compounds. Of the twenty essential amino acids, L-lysine, L-glutamic acid, and L-aspartic acid are asymmetrical AB2 molecules, but the bulk of the research into highly branched poly(amino acid)s has focused on the polycationic poly(L-lysine) with a lesser extent on poly(L-glutamic acid). Hence, the majority of potential applications lies in delivery systems for nucleic acids and this review examines and compares how these three types of highly branched polymers function as non-viral gene delivery vectors. When considering drug delivery systems, the small size of these highly branched polymers is advantageous for the delivery of inhalable drug. Even though highly branched polymers, in particular dendrimers, have been studied for more than 40 years for the delivery of genes and drugs, they have not translated in large scale into the clinic except for promising antiviral applications that have been commercialized.

Local Orientational Mobility of Collapsed Dendrimers

“…The first dendrimers were synthesized in the late 70s and early 80s of the last century. − Lysine and peptide dendrimers consisting of amino acid residues, − or hybrid dendrimers, for example, polyamidoamine (PAMAM) and polypropylene (PPI) dendrimers, which have terminal groups functionalized with amino acid residues, − are of great importance for biomedical applications. The most popular terminal amino acid residues for functionalization are positively charged lysine and arginine residues, as well as histidine. − The latter, depending on the pH of the medium, can be positively charged or neutral, and the conformations of the corresponding dendrimers are swollen or collapsed. It should be noted that in lysine and peptide dendrimers not only terminal but also internal groups can be functionalized by inserting amino acid residues between adjacent branching points of the dendrimer. , …”

Advances in the polymeric delivery of nucleic acid vaccines

“…After intramuscular injection, DGLs prevented pDNA degradation, assisted pDNA escape from endosomes, promoted antigen presentation, and induced effective cellular and humoral immune responses, thereby demonstrating that DGLs were good non-viral nucleic acid vaccine delivery carriers 32 . To increase positive charge densities in the polymer structure, considerable attention has been paid to the development of highly branched poly(amino acid)s as gene delivery vectors 33 , which will also show great potential in vaccine delivery.…”

Blocking viral infections with lysine-based polymeric nanostructures: a critical review

“…Depending on the characteristics of these structures, such as size, geometry, and degree of polymerization, it is possible to endow the polymeric structure with precise functional characteristics for different biomedical applications, in diagnostic, drug and gene delivery, theranostic. [65][66][67] The molecular weight of dendrimers grows faster than the molecular volume and they exhibit a high concentration of terminal groups in a relatively small volume. 41 The surface charge becomes, therefore, a key parameter to govern the interaction with other biological structures.…”