293
polymers were used for promoting the solubilization of several drugs. The first bioavailability study using a soluble cyclodextrin polymer was reported in the mid-1980s
(Uekama et al. 1985). The absorption-promoting effect of the soluble cyclodextrin
polymer on the sublingual route was also demonstrated in the case of steroids (Pitha
et al. 1986). Karadake et al. (1982) showed that the drug release was retarded and the
stability against oxidation and degradation was greatly increased when penicillin complexed with soluble cyclodextrin polymer was microencapsulated. In those years, the
safety of these new materials was obviously a concern, so its innocuity was checked.
Practically no hemolytic effects were observed when compared to natural or methylated cyclodextrins.
On the other hand, some applications of the insoluble cross-linked cyclodextrin
polymer were also investigated. For instance, its effect on wound healing was tried
on tissues of rats (Felméray et al. 1996). In addition, the cyclodextrin- epichlorohydrin
sorption capabilities were tested for the removal of phenylalanine from a protein
hydrolysate in order to make it digestible for children suffering from phenylketonuria (Specht et al. 1981). Also at that time, the effectiveness of a cyclodextrin polymer as a tablet disintegrant was studied in direct compression systems (Fenyvesi
et al. 1984).
Those first attempts to show their capabilities in the sorption and release of aromatic model molecules pointed to the use of cyclodextrin polymers as controlled
release agents (Friedman et al. 1989). Specifically, the release of cetylpyridinium
chloride (an antimicrobial agent) and iodine, using cyclodextrin polymers, was patented in the late 1980s (Friedman 1988; Szejtli et al. 1988). An earlier example of a
cyclodextrin polymer as a macromolecular carrier in the field of antitumor chemotherapy was published also in the mid-1980s (Kaji et al. 1985). In that work, a bifunctional delivery system composed of mixed micelles and a complex between the drug
(1-hexylcarbamoyl-5-fluorouracil) and cyclodextrin polymer was tested.
The following decade showed only a few other distinct examples of the applicability of cyclodextrin polymers in the field of drug delivery. Thus, drugs complexed in
cyclodextrin polymers were entrapped into liposomes. The latter present some problems in the accommodation of water-insoluble drugs in their lipid bilayers, so the new
formulation using cyclodextrin polymer could circumvent such limitations
(McCormack and Gregoriadis 1994). On the other hand, the need to prepare degradable materials for medical applications, including drug delivery, associating networks
using cyclodextrin-epichlorohydrin polymers and degradable copolyesters containing
adamantyl groups were tested and were shown to be pH sensitive (Cammas et al. 1999).
Cyclodextrin-based nanosponges, prepared by cross-linking reactions using
either condensation or interfacial polymerization reactions, are biocompatible nanoporous nanoparticles. They have been designed in the last years to increase the dissolution rate, the solubility, and stability of drugs, to prolong the release time, and
also applied in semisolid formulations for skin delivery (Ansari et al. 2011; Shende
et al. 2013; Conte et al. 2014).
As mentioned above, cyclodextrin moieties can be incorporated to pre-existing
polymeric materials via grafting reactions. In most of the drug delivery applications,
cyclodextrins are attached to polysaccharides (Luzardo-Alvarez et al. 2014), such as
6 Cyclodextrin-Based Polymers for Food and Pharmaceutical Applications…
polymers were used for promoting the solubilization of several drugs. The first bioavailability study using a soluble cyclodextrin polymer was reported in the mid-1980s
(Uekama et al. 1985). The absorption-promoting effect of the soluble cyclodextrin
polymer on the sublingual route was also demonstrated in the case of steroids (Pitha
et al. 1986). Karadake et al. (1982) showed that the drug release was retarded and the
stability against oxidation and degradation was greatly increased when penicillin complexed with soluble cyclodextrin polymer was microencapsulated. In those years, the
safety of these new materials was obviously a concern, so its innocuity was checked.
Practically no hemolytic effects were observed when compared to natural or methylated cyclodextrins.
On the other hand, some applications of the insoluble cross-linked cyclodextrin
polymer were also investigated. For instance, its effect on wound healing was tried
on tissues of rats (Felméray et al. 1996). In addition, the cyclodextrin- epichlorohydrin
sorption capabilities were tested for the removal of phenylalanine from a protein
hydrolysate in order to make it digestible for children suffering from phenylketonuria (Specht et al. 1981). Also at that time, the effectiveness of a cyclodextrin polymer as a tablet disintegrant was studied in direct compression systems (Fenyvesi
et al. 1984).
Those first attempts to show their capabilities in the sorption and release of aromatic model molecules pointed to the use of cyclodextrin polymers as controlled
release agents (Friedman et al. 1989). Specifically, the release of cetylpyridinium
chloride (an antimicrobial agent) and iodine, using cyclodextrin polymers, was patented in the late 1980s (Friedman 1988; Szejtli et al. 1988). An earlier example of a
cyclodextrin polymer as a macromolecular carrier in the field of antitumor chemotherapy was published also in the mid-1980s (Kaji et al. 1985). In that work, a bifunctional delivery system composed of mixed micelles and a complex between the drug
(1-hexylcarbamoyl-5-fluorouracil) and cyclodextrin polymer was tested.
The following decade showed only a few other distinct examples of the applicability of cyclodextrin polymers in the field of drug delivery. Thus, drugs complexed in
cyclodextrin polymers were entrapped into liposomes. The latter present some problems in the accommodation of water-insoluble drugs in their lipid bilayers, so the new
formulation using cyclodextrin polymer could circumvent such limitations
(McCormack and Gregoriadis 1994). On the other hand, the need to prepare degradable materials for medical applications, including drug delivery, associating networks
using cyclodextrin-epichlorohydrin polymers and degradable copolyesters containing
adamantyl groups were tested and were shown to be pH sensitive (Cammas et al. 1999).
Cyclodextrin-based nanosponges, prepared by cross-linking reactions using
either condensation or interfacial polymerization reactions, are biocompatible nanoporous nanoparticles. They have been designed in the last years to increase the dissolution rate, the solubility, and stability of drugs, to prolong the release time, and
also applied in semisolid formulations for skin delivery (Ansari et al. 2011; Shende
et al. 2013; Conte et al. 2014).
As mentioned above, cyclodextrin moieties can be incorporated to pre-existing
polymeric materials via grafting reactions. In most of the drug delivery applications,
cyclodextrins are attached to polysaccharides (Luzardo-Alvarez et al. 2014), such as
6 Cyclodextrin-Based Polymers for Food and Pharmaceutical Applications…