Application of Chitosan-Based Gels in Pharmaceuticals - Chitosan Based Hydrogels: Functions and Applications - page 320

a decapeptide, is a naturally occurring hormone that controls human sex hormones. Numerous
LH-RH analogues (TX46) have been synthesized to manipulate the menstrual cycle and treat
various steroid-dependent disorders, sex-hormone-dependent cancers and gynecological
conditions [26]. A novel kind of chitosan microparticles has been prepared to prevent TX46
degradation by proteases or other enzymes [27]. Insulin-loaded chitosan microparticles have
been prepared by combining a membrane emulsification technique and a stepwise cross-
linking method. The chitosan microparticles showed high encapsulation efficiency (80%),
high chemical stability of insulin (>95%), low burst release, and steady release behavior [28].
Chitosan gel beads prepared with chelated copper (II) ions are vehicles for the delivery of
peptide and protein drugs, and have been studied for the release of insulin as well. In this
study, insulin was scarcely released from the chitosan gel beads in vitro , which was proposed
to be due to the interactions occurring among insulin, chitosan, and copper (II) ions. The effi-
cacy of insulin released from the chitosan gel beads was confirmed by implantation into
diabetic mice [29]. Human growth hormone encapsulated in chitosan microparticles has also
been shown to be effective in early bone consolidation in distraction osteogenesis [30].
7.4.1.2 Enzyme Delivery
Chitosan is known as an ideal support material for enzyme immobilization because of its
characteristics, such as improved mechanical strength, resistance to chemical degradation,
protection of enzymes from the action of metal ions, and antibacterial properties. In
D. S. Jiang's study, laccase immobilized on magnetic chitosan microcarriers improved the
performance of a fiber optic biosensor of oxygen consumption in relation to analyte oxida-
tion, and was reported to have potential applications in medical examination and diagnos-
tics [31]. Catalase is another enzyme that has been immobilized, by a phase-inversion method
[32], with sulfoxine as a chelating resin fixed to CMs acting as a support matrix [33].
7.4.1.3 Gene Delivery
Gene therapy refers to the transmission of DNA encoding a therapeutic gene of interest into
the targeted cells or organs with consequent expression of the transgene. In efficient gene
delivery, plasmid DNA is introduced into target cells and transcribed and the genetic infor-
mation is ultimately translated into the corresponding protein. In order to achieve that goal,
the gene delivery system has to overcome a number of obstacles (Figure 7.8) [34].
Transfection is hampered by (a) targeting the delivery system to the target cell, (b) trans-
porting DNA through the cell membrane, (c) being uptaken and degraded in endolyso-
somes, and (d) intracellular trafficking of plasmid DNA to the nucleus. Gene delivery
systems include viral vectors, cationic liposomes, polycation complexes, and microencap-
sulated systems [35-38]. Viral vectors are advantageous for gene delivery because they are
highly efficient and have a wide range of cell targets. However, when used in vivo , they
cause immune responses and oncogenic effects. In addition, sometimes it is difficult to
reproducibly prepare viral vectors in large batches. To overcome the limitations of viral
vectors, nonviral delivery systems based on chitosan are considered for gene therapy.
Some of the advantages of chitosan-based delivery systems are listed below [39]:
1. Conjugation of ligands to the nanospheres, for targeting or stimulating receptor-
mediated endocytosis.
2. Incorporation of lysosomolytic agents to reduce the degradation of DNA in the
endosomal and lysosomal compartments.