Biomedical Engineering Reference
In-Depth Information
interaction with blood components and phagocytic cells raises a question about the optimal
surface modifi cation of the particulate carriers [75]. PEO has been the most successful synthetic
material used to modify the interactions of solid surfaces with biological media. This fact has been
demonstrated for particulate carriers with either grafted PEO or adsorbed amphiphilic PEO-based
copolymer, liposomes with incorporated PEO derivatives, and biomedical implants with grafted
PEO chains.
It is evident from the results with both nonbiodegradable and biodegradable systems that the
surface modifi cation of particulate carriers by the creation of a coating layer composed of PEO
chains can result in the avoidance of the physiological processes that would normally occur after
parenteral administration of the particles. As injected particles interact with the body components
through their surface, the surface properties of the successful model system (e.g., surface chemistry,
hydrophilicity, surface charge, coating layer thickness, and arrangements of the PEO chains on the
surface) have been extensively studied [75].
The capacity of PEO to repel proteins and not interact with macrophage plasma membrane
largely depends on different parameters such as molecular weight, density, and conformation and
fl exibility of the chains [78]. Illum et al. showed that for the effective stabilization of colloidal
drug delivery system, it is essential that the dimensions of the stabilizing polymer chains exceed
the range of the van der Waals attraction forces. Many studies showed that the protein adsorption
decreased with the increase of molecular weight and an effi cient molecular weight in the range
of 1500-3500 Da. [79]. A good protection can be obtained after reaching the critical minimum
coating layer thickness, which also depends on the size of adsorbed proteins. With this aim, the
increase in size of colloidal drug delivery system is generally accompanied by an increase of the
molecular weight of the PEO chain. Pavey and Olliff suggested that a more effi cient system would
be a mixture of PEO lengths because the longer chains would be a mixture of PEG lengths as they
would be less inhibited in their movement, and the shorter chains would be interdigitated close to
the surface for optimal recovery [80].
Another parameter described as a key factor in the optimization of PEO modifi cation is the
density of PEO chains. The higher the density, the faster the proteins are repelled from the polymer
structure, the lower the protein adsorption, and the greater the difference of adsorbed protein
composition [78]. However, Gref et al. suggested that whatever the thickness or the density of the
coating, the qualitative composition of the plasma protein adsorption patterns were very similar,
showing that adsorption was mainly governed by interactions with a colloidal drug delivery system.
It could be explained that the molecular weight and the density are important criteria that are
related to each other and can compensate each other in order to create a suffi cient thickness limiting
interactions with proteins and macrophages [81].
In addition, the interaction with proteins is infl uenced by the conformation of the PEO coating.
PEO produces a surface that is in a liquid-like state with the polymer chains exhibiting considerable
fl exibility and mobility. The high mobility of PEO chains has been proposed to repel approaching
proteins from the surface because the protein does not have suffi cient contact time with the mobile
chains to adsorb. Furthermore, the reduced mobility of the PEO chains on a highly crowded surface
(produced by grafting of branched PEO derivatives) has been suggested as the reason for higher
protein adsorption on this system relative to the surface modifi ed with linear PEO chains [75].
Many studies showed that stealth properties were governed by many interdependent parameters.
A parameter can compensate for others and lead to a satisfying system. It could be suggested that
in order to have a prolonged time in blood, colloidal drug delivery system must preferentially be
small, composed of natural and hydrophilic surface. The coating of hydrophilic polymer chains has
to be dense and fl exible to reduce all kinds of interactions [78]. But above all, the coating must be
organized so as to minimize contact with bare hydrophobic surface of the colloidal drug delivery
system, and well-anchored in the colloidal drug delivery system core in order to avoid desorption of
chains caused by opsonization [82].
