Polyamines drug delivery

Nabeshima, Y., Ding, Z. L., Chen, G. H., Hoffman, A. S., Taira, H., Kataoka, K., and Tsuruta, T., Slow release of heparin from a hydrogel made from polyamine chains to a temperature-sensitive polymer backbone, in Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems (N. Ogata, et al., Eds.), pp. 315-316. Springer, Tokyo (1996). 

Likewise, due to their cationic properties polyamine moieties were found to enhance water solubiUty and cellular uptake of many therapeutic molecules, making them potential drug delivery agents. For most of the properties of polyamines the biological mechanisms are not well understood or are still in debate. Therefore, current research on natiu al and synthetic polyamines requires the synthesis of those compounds and many derivatives to investigate their function and to gain novel mimics for therapeutic applications. 

Most polymer-based carriers for the delivery of nucleic acid drugs must escape the endosomes before complete acidification, which activates lysosomal digestion. After the discovery of the powerful endosomal destabilization activity of PEI [66], many polymer-based carriers have mimicked the structure of PEI for endosomal escape. As explained in Sect. 3.2, the proton-sponge effect of xmprotonated tertiary amines and direct contact of protonated polyamines with the endosomal membrane are two possible mechanisms of endosomal disruption by PEI. Because pH-dependent protonation is critical in both mechanisms, polymers with a high density of protonable amines during the early endosomal acidification firom pH 7.4 to 5.5 are one of the main kinds of polymer-based carriers with an endosomal escape function. Like tertiary amines in PEI, protonable moieties with low p Ta values have been frequently introduced into the polymer-based carriers. An imidazole moiety with pA"a of around 6.0 was one such candidate. The introduction of polyhistidine with an imidazole moiety on a PLL backbone showed significant increase in endosomal escape efficiency [169]. 

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