Biomedical applications polymer-drug conjugates

Jeffamine M-1000 increases the pH and hemolytic activities [34]. Modifying the side chains with amino acids valine, leucine, and phenylalanine imparts pH-responsive properties onto the polymer, which could be useful for many biomedical applications [36]. Polymers with PEG side chains have been developed into micelles and show enhanced uptake in spheroids formed with HeLa cells [37]. These polymers have also been conjugated to fluorescent dyes, which could be used for drug-tracking applications [38,39]. 

A famous example of multifunctionality in polymeric materials for biomedical applications is the concept of polymer-drag conjugates as introduced by Ringsdorf in 1975 [3] (Fig. 5.2). The various functionalities are introduced by a combination of copolymerization and polymer analogous reactions. It has to be noted that for drug delivery carrier polymers, not only the functionality but also the molar mass are of high importance for the apphcation since it defines not only the solubihty but also the half-life time in blood and the uptake in specific cells and the excretion from the kidneys. 

Lewis et al. were able to form bioconjugates using a bis-sulfone polymer. Conjugation of NHS end-functionalized 2-methacryloyloxyethyl phosphorylcho-line (MPC) to interferon (IFN)-a2a was unsuccessful, so a different route to create bioconjugates was required. Poly MPC has been used in a wide range of biomedical applications, notably in the solubilization of drugs such as paclitaxel and amphotericin A bis-sulfide initiator... 

Unless a carrier conjugate can fulfill the prerequisities listed under (1), (2) and (3), its usefulness is severely limited. Only when a carrier meets requirements (l)- 3) is it necessary to consider the clinical implications of (4) and (5). Fig. 4 illustrates the basic requirements of the polymeric carrier and the characteristic of both a linear and crosslinked polymer. In the following section examples of soluble synthetic polymers specifically synthesized with respect to biomedical applications are given and the importance of their properties relative to polymeric drug carriers is discussed. 

A key physiochemical trait of chitosan is its unique molecular structure, which contains abundant reactive hydroxyl and amino functional groups. These functional groups provide anchor sites for further conjugation of functional molecules to chitosan. The abundant amino functional groups present in the molecular structure of chitosan also ensure a net cationic character, which enables electrostatic com-plexation with anionic drugs and biotherapeutics. Combined, these functionalities render chitosan highly amendable to further modification, and a desirable polymer platform for a broad range of biomedical applications. 

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