Cross-links are bonds that link one polymer chain to another. These bonds can
either be covalent or ionic in nature. In polymer science, the use of cross-links to promote a
difference in a polymer’s physical properties is referred to as cross-linking. When polymer
chains are linked together by cross-links, they lose some of their ability to move as individual
polymer chains. For example, a liquid polymer, which possesses freely flowing chains can be
turned into a “solid” or “gel” by cross-linking the chains together. Cross-linking inhibits close
packing of the polymer chains, preventing the formation of crystalline regions. The restricted
molecular mobility of a cross-linked structure limits the extension of the polymer material
under loading. This means that when a polymer is stretched, the cross-links prevent the
individual chains from sliding past each other. In the process, the chains may straighten out,
but once the stress is removed they return to their original position and the object returns to its
original shape. It is a well known fact that polymers with a high enough degree of crosslinking
have “memory”. With this “memory”, such cross-linked polymers can be exploited for
a number of useful purposes including modifications for improved drug delivery and release.
Several reports have indicated that the cross-linking density, molecular weight, electrical
charge of polymers and other factors might have a profound effect on the release rate of drugs
from polymer-based multiparticulate drug delivery systems. Among these factors, the
modification of the cross-linking density is expected to be the most useful for optimizing the
release rate of drugs, including peptides, from such systems. Alteration of the cross-linking
conditions almost always results in changes in the cross-linking density of biopolymers. Both
the prolongation of the cross-linking reaction time and an increase in concentrations of crosslinking
agent have been reported to increase the cross-linking density of gelatin and other
biopolymers. These reports suggest that polymers with desirable cross-linking density could
be obtained by optimizing the conditions of the cross-linking reaction. The cross-linking
density of polymers such as alginate and collagen could also be altered by modifying the
cross-linking reaction time and the concentration of the cross-linking agent. In fact, previous
reports have demonstrated that as the cross-linking density became higher, the amount of
insulin released from gelatin microspheres in the initial phase decreased. A burst release of
insulin, however, was also reported for gelatin microspheres with a low cross-linking density
because of the structural weakness of such microspheres. This chapter will, therefore, focus on
how drug delivery and release can be improved and/or controlled by altering the cross-linking
density of biopolymers using well known polymers as illustrations. Optimization of this
technique would be useful when designing biopolymer-based multiparticulate systems for
drug delivery.
