Recent Progress in Polymer Therapeutics as Nanomedicines - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 81

design versatility by allowing systematic variation of the distribution
of active units along a polymer chain. Thus, copolymers can be
tailor-made in order to vary hydrophilicity or lipophilicity of the
entire molecule or of single domains (block systems), or to introduce
various functional groups. Properties of the microenvironment in a
polymer coil diff er drastically from those of the bulk solution and are
dictated mainly by monomers composition.
Since our final goal is to use these materials as carriers for
pharmaceuticals, some criteria must be met: The polymeric
nanocarriers should be biocompatible and non-toxic, and they should
avoid interaction with the immune system (unless it is the target), to
enable repeated administration. In addition, biodegradable polymers
are favored for better clearance from the body. Finally, many groups
choose to work with FDA-approved polymers, to facilitate the
approval for clinical use of their system. In any way, all polymer
therapeutics are considered new chemical entities (NCE) from the
regulatory point of view. The most common polymers used in the
field of polymer therapeutics are listed in Table 4.1. We will focus
on several polymers, which are in early clinical trials as polymeric
nanocarriers for anti-cancer agents [9].
For a suitable conjugation to chemical and biopharmaceutical
drugs, many polymers have been proposed as carriers,
including N-(2-hydroxypropyl)methacrylamide (HPMA)
copolymers, poly(ethyleneimine) (PEI), linear polyamidoamines,
polyvinylpyrrolidone (PVP), polyglutamic acid (PGA), polyacrylamide
(PAAm), polydimethylacrylamide (PDAAm), polyvinyl alcohol (PVA),
chitosan, and dextrin. It is important to note that polyethylene glycol
(PEG) has significant contribution specifically in the field of polymer-
protein conjugates, as will be discussed later on. PEGylation has
been proven to be one of the most straightforward procedures for
enhancing the therapeutic and biotechnological potential of peptides
and proteins [10].
The diff erent types of polymer backbones can be divided into
two sub-groups according to the feature of biodegradability in the
main chain.

4.1.2 Degradable Polymers Backbone

PGA is synthesized by ring-opening co-polymerization of the
corresponding N-carboxyanhydrides (NCA), initiated by amines