AUTHOR
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Various carriers have been developed for local or systemic delivery of small-molecule drugs and biologics. The general approaches
include liposomes (1–2), copolymer micelles (3), hydrogels (4), microemulsion-based media (5), dendrimers (6), cyclodextrins
(7), pectin (8), tocols (9), and synthetic polymer microspheres (10). The materials used to make these carriers are called
biomaterials (11). The US Food and Drug Administration, and therefore the entire industry, is shifting increasingly away from
poorly-defined biomaterials that may include animal products to highly-defined, animal-component-free biomaterials. Control
over structure and origin has long been a selling point of synthetic polymer-based materials for use in vivo. Pertinent concerns in the development of a biomaterial for drug delivery include biocompatibility, efficiency of drug loading,
and timescale of drug release. A broad range of methods has been developed to characterize the physical, chemical, and biological
properties of biomaterials (12). Some FDA-approved biomaterials lead to side effects in some applications. The breakdown products
of poly(lactide-co-glycolide) microspheres, for instance, are highly acidic, lowering the local pH and increasing the severity
of inflammation in tissues (13). For such reasons the level of interest in developing novel biomaterials has never been greater.
Polypeptide multilayer nanofilms (PMNs) have recently been developed as multifunctional biomaterials (14). Surprisingly, perhaps,
the earliest work on PMNs was for optical coatings (15) and electrochemical electrode coatings (16). It was later proposed
to make PMNs out of derivatives of poly(L-lysine) in which "functional" peptides, for example hormone molecules, were grafted
onto monomer side chains via the free amino group (17). PMNs are polyelectrolyte multilayer films made largely if not entirely
of polypeptides (14).
Polypeptides are interesting for biomaterials development because they are "natural." Peptides constitute half of the dry
mass of an organism and they are biodegradable. Moreover, peptides can exhibit extremely high biological specificity and their
breakdown products are generally not only benign, but indeed useful as food (18). Furthermore, polypeptides can be designed;
an astronomical number of chemically different peptide structures can be realized, and a large number of different peptides
can be prepared in huge quantities by various methods (19–20). Peptides designed for PMN fabrication can be protein inspired
(21).
Polyelectrolyte multilayer films were first studied systematically by Decher and colleagues (22–23). Polyelectrolytes suitable
for multilayer film fabrications can be classified as "strong" or "weak," depending on how they are affected by pH. "Strong"
polyelectrolytes show limited dependence on pH, "weak" polyelectrolytes the opposite (24). Polypeptides are weak polyelectrolytes.
The isoelectric point of a peptide, the pH at which its net charge equals 0, is a strong function of amino acid composition
(25). The author's research group has performed studies to determine how the PMN architecture can be altered with changing
pH.
Construction parameters
Figure 1
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PMNs are fabricated by electrostatic layer-by-layer self-assembly (LBL). The method is simple and repetitive (see Figure 1).
Electrostatic interactions enable and limit polymer adsorption. Electrostatic attraction holds peptides together between layers,
and electrostatic repulsion drives peptides apart within a layer. As a result, the researcher can control layer thickness
to within about 1–10 nm. The LBL method is versatile. Many different chemical species are suitable. The method is environmentally
benign: The most useful solvent for most current applications of LBL is water.
