Biomedical Engineering Reference
In-Depth Information
Chen et al. [39] investigated the drug release behaviors from a monolithic membrane prepared
by Ca-defi cient hydroxyapatite (CDHA)/chitosan nanocomposite. A higher value of diffusion expo-
nent ( n ) was obtained for the membranes that were in situ synthesized compared with those that
were ex situ prepared. In addition, the n value of the membranes that were in situ synthesized
increased with increasing CDHA amount, which remained in the range below 10 wt.%. However, as
CDHA content exceeded 30%, the n value remained constant. The drug diffusion mechanism was
altered by the CDHA-chitosan interaction, which was strongly infl uenced by both the preparation
process and the concentration of the CDHA nanofi ller in the membrane. A lower permeability ( P )
value of the membranes was observed for those membranes prepared by the in situ process. Further-
more, the P value decreased and increased with increasing CDHA amount in the range below and
above 10 wt.%, respectively. These results indicated that CDHA nanofi llers acted as either diffusion
barrier or diffusion enhancer for the CDHA/chitosan membranes, which was determined by the
concentration of CDHA nanofi ller and the preparation route of the nanocomposite.
The properties of gelatin HA as drug-delivery carriers for tissue-regeneration and wound-healing
treatments have also been investigated [40]. The gelatin-HA nanocomposite porous scaffolds were
prepared by casting the solutions containing HA and gelatin and further freeze-drying. The bodies
obtained were cross-linked with carbodiimide derivatives to retain chemical and thermal integrity.
The apatite precipitates were poorly crystallized carbonate-substituted HA. The nanocomposite
scaffolds had porosities of about 89-92% and exhibited a bimodal pore size distribution, that is, the
macropores (300-500 µm) of the framework structure and the micropores (0.5-1 µm) formed on the
framework surface. Elongated HA nanocrystals were formed on gelatin network. Tetracycline, an
antibiotic drug, was entrapped within the scaffold, and the drug-release properties were examined
with preparation parameters such as HA amount in gelatin, cross-linking degree, and initial drug
addition. The drug entrapment decreased with increasing HA amount, but increased with increas-
ing cross-linking degree and initial drug addition. The cross-linking of gelatin was the prerequisite
to sustaining and controlling the drug release. Compared with pure gelatin, the gelatin-HA nano-
composites had lower drug releases because of their lower water uptake and degradation. All the
nanocomposite scaffolds released drugs in proportion to the initial drug addition, suggesting their
capacity to deliver drugs in a controlled manner.
9.4 MAGNETIC TARGETING DRUG DELIVERY SYSTEMS
A major disadvantage of most of the conventional chemotherapeutic approaches is their nonspeci-
fi city. Therapeutic (generally, cytotoxic) drugs are administered intravenously, leading to a gen-
eral systemic distribution of drugs. The nonspecifi c nature of these techniques causes side effects
because the cytotoxic drug attacks normal, healthy cells in addition to tumor cells.
Currently, there is an increasing interest in the development of magnetic nanostructures for bio-
medical applications [41,42]. Because of their response to the magnetic fi eld, magnetic nanostruc-
tures are very promising for application in targeted drug delivery. The magnetic nanoparticle-based
targeting can reduce or eliminate the side effects of conventional chemotherapy by reducing the
systemic distribution of drugs and lower the doses of the cytotoxic compounds. Dobson [43] pub-
lished a short review on the technical aspects of magnetic targeting as well as nanoparticle design
and animal and clinical trials.
The idea of using magnetic micro- and nanoparticles to act as therapeutic drug carriers to
target specifi c sites in the body dates back to the late 1970s [44-46]. Widder and others [44]
developed magnetic micro- and nanoparticles to which cytotoxic drugs could be attached. The
drug-carrier complex was injected into the subject through either intravenous injection or intra-
arterial injection. High-gradient, external magnetic fi elds were used to guide and concentrate the
drugs at tumor locations. After the magnetic carrier was concentrated at the tumor or another tar-
get in vivo , the therapeutic agent was released from the magnetic carrier through either enzymatic
 
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