Biomedical Engineering Reference
In-Depth Information
might limit its long-term applications. Thus, a possible alternative for PEG is
desired.
In fact, there are two major classes of materials to resist nonspecific protein
adsorption, so-called ''nonfouling'' materials, namely hydrophilic polymers and
zwitterionic polymers. A number of ''nonfouling'' hydrophilic polymers,
including PEG, polysaccharides, and polyamides, have been found to mostly
share some common structural and chemical properties: hydrophilic nature,
electrical neutrality, and hydrogen-bond acceptors/donors.
11,12
They have been
fully investigated for drug delivery due to their significant improvement in
protein compatibility and the convenience of preparing copolymers with highly
hydrophobic segments. In recent years, zwitterionic polymers, such as poly
(2-methacryloyloxyethyl phosphorylcholine) (pMPC),
13-15
poly(sulfobetaine
methacrylate) (pSBMA),
16,17
poly(carboxybetaine methacrylate) (pCBMA),
18,19
or simply mixed charge materials,
20,21
have been recognized as superior materials
to resist nonspecific protein adsorption, and which can maintain the stability
of nanoparticles or micelles in highly complex media such as undiluted serum
where PEG coatings fail to stabilize nanoparticles under the same conditions.
22
Furthermore, carboxybetaine (CB)-based zwitterionic polymers are able to
conjugate bio-recognizable ligands or antibodies without losing their resistance.
Moreover, excellent hemocompatible surfaces resisting the adhesion of blood
platelets and highly efficient drug carriers have been achieved by the protection of
zwitterionic polymers in recent years, and methods to utilize zwitterionic
polymers have been explored. The molecular weight of homopolymers or block
copolymers can be well controlled in a narrow range through living radical
polymerization.
23
Surface-initiated polymerization could also improve the
protection of nanoparticles with fewer drawbacks.
22
In short, zwitterionic
polymers could be potential alternatives to PEG for a broad range of
applications. Table 10.1 shows the zwitterionic materials found in the literature.
In this chapter, we mainly discuss the unique properties of zwitterionic
polymers and their applications in nanomedicine, although this is a rather small
amount of work compared with their ''nonfouling'' hydrophilic polymer-related
applications in nanomedicine. The application of zwitterionic polymers on
macroscale surfaces, such as blood contact tubules, filters, or stents, will not be
reviewed here, although the original motivation for inventing and exploring the
zwitterionic polymers coatings was to obtain excellent hemocompatibility of
macro scale surfaces.
24,25
Comprehensive reviews about the design principles
and biological applications of ''nonfouling'' materials can be found in previous
publications,
20,26
which might provide a broad view through extended reading.
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10.2 Principles Toward Protein-Resistant Zwitterionic
Polymers
To understand the advantages of zwitterionic polymers for drug delivery
systems, the capability in the resistance to nonspecific protein adsorption of
polymers should be considered first of all. Although PEG exhibits resistance to
