Biomedical Engineering Reference
In-Depth Information
to the polymer phase. The nanoparticles were collected and washed in
n
-haxane, suspended in a
solution of PVA to prevent fusion and aggregation of the particles, and freeze-dried to produce a
powder of nanoparticles approximately 700 nm in diameter [74]. Although the particles produced
were still nanoscale, there was a substantial difference in the size of the particles produced using
the two different techniques. When fabricating particulate carrier systems for oral drug delivery
systems, particularly those intended for vaccine delivery, consideration should be given to the dif-
ferent particle sizes resulting from alternative fabrication techniques, as this may have implications
for their effi cacy in clinical applications. One example is the particle size-dependent exclusion phe-
nomenon that exists in gastrointestinal mucosal tissue, where nanoparticles in the region of 100 nm
show signifi cantly greater uptake compared with larger nano/microparticles [75].
In addition to avoiding rapid elimination from the colon, nanoparticles also have the additional
attribute of accumulating at sites of infl amed tissue, which could be used to facilitate the targeting
of anti-infl ammatory drugs to sites of colonic infl ammation. This phenomenon is thought to occur
through the uptake of nanoparticles by immune cells infi ltrating the tissue and adhesion to the
excessive amounts of mucus secreted in infl amed tissue, increasing the localization of drug delivery
[76]. The selective delivery achievable with nanoparticle systems can therefore be applied to reduce
the risk of severe adverse side effects associated with systemic administration of certain drugs and
to achieve increased effi ciency and tolerability [72].
Further selective drug delivery using nanoparticles has been achieved with pH-sensitive
polymers developed for colonic drug delivery, whereby drug release is controlled by the sensitivity
of the polymer to lumenal pH during intestinal passage [72]. The nanoparticles were prepared using
an oil-in-water emulsifi cation-solvent evaporation process. The pH-sensitive polymer (Eudragit
P-4135F, Röhm Pharma Polymers, Japan) was dissolved in methylene chloride together with the
immunosuppressant drug (tacrolimus). The solution was added to a 1% (w/w) solution of polyvinyl
alcohol to form an oil-in-water emulsion using ultrasonication. The solvent was removed under
reduced pressure, and the nanoparticles were washed in distilled water prior to freeze-drying in
a 5% sucrose solution. The nanoparticles produced were approximately 450 nm in diameter and
had high encapsulation effi ciencies. Although the pH-sensitive nanoparticles and control (non-pH-
sensitive) poly(lactic-
co
-glycolic acid) nanoparticles reduced the levels of adverse effects associ-
ated with systemic delivery of the drug, such as nephrotoxicity, in the mouse model of colitis used
in the study, it is worth noting that the nanoparticle formulations were a less effective treatment
for the control of the experimental colitis compared with subcutaneous delivery of the drug. This
study illustrates the situation that frequently arises with the development of new “smart” materials.
Although these new materials may solve one problem, they may give rise to additional problems
that require further modifi cation of the material.
20.7
BIOMATERIALS FOR INTESTINAL TISSUE ENGINEERING
20.7.1 I
NTESTINAL
F
AILURE
AND
T
ISSUE
E
NGINEERING
The intestine plays an essential role in maintaining the nutritional status of humans. A number of
diseases can signifi cantly disrupt the normal function of the intestine, resulting in a condition called
intestinal failure. Children and adults with intestinal failure have a poor quality of life and suffer
signifi cant morbidity and mortality. This condition usually results in the patient receiving artifi cial
feeding in the form of intravenous (parenteral) nutrition. In the United Kingdom, it is estimated that
20,000-25,000 adults and children are receiving long-term home parenteral nutrition at any point
in time and that this fi gure is increasing by approximately 20% annually. Surgical options, such as
transplantation, are reserved for patients with potential or actual life-threatening complications of
parenteral nutrition due to the scarcity of donor organs, the side effects from immunosuppression,
and much lower survival rates than from parenteral nutrition.
