Biomedical Engineering Reference
In-Depth Information
coating of poly(styrene) nanoparticles caused a decrease of gastrointestinal uptake in vivo . More-
over, hydrophobic poly(styrene) nanoparticles seem to have a higher affi nity for M-cells than for
absorptive epithelia [49]. Another factor that infl uences the particle uptake is the surface charge.
Generally, positively charged particles have higher uptake as compared with the negatively or neu-
trally charged species. Carboxylated poly(styrene) nanoparticles show signifi cantly decreased affi n-
ity to intestinal epithelia, especially to M-cells, compared with positively charged and uncharged
poly(styrene) nanoparticles [43].
Specifi c strategies are being proposed to enhance the intestinal uptake of nanoparticles. These
strategies include the surface modifi cation of nanoparticles with some targeting ligands such as lec-
tins. Lectins can be defi ned as proteins of nonimmune origin that bind to carbohydrates specifi cally
and noncovalently. Lectins can increase the adherence of nanoparticles to the intestinal epithelium
[50]. After binding to the cells, the lectins undergo cellular uptake and subsequently can also exhibit
strong binding to nuclear pore membranes. Polystyrene microparticles coated with tomato lectin
were shown to be specifi cally adhesive to enterocytes [51].
Major questions to be asked here are as follows:
1. Is particle uptake suffi cient enough to achieve therapeutic effectiveness?
2. Are biodegradable polymer nanoparticles capable of preserving the delicate structure of
sensitive peptide drugs?
3. Are these particle systems safe for long-term therapeutic use?
The fi rst and most important question to be asked here is whether the absorption of drug carriers via
normal enterocytes and M-cells is suffi cient to allow therapeutic effectiveness. This uptake may be
corelated with the low percentage of M-cells present in the gut (0.1% of the epithelial cells), which
may be insuffi cient to get an appreciable amount of bioavailability. Another major issue associated
with solid-delivery systems is adsorption of proteins onto these solid-delivery devices [52]. The
incorporation of peptides-based pharmaceuticals into solid-delivery matrices exposes them to a
high surface to volume environment, creating ample opportunity for adsorption into the delivery
devices. Adsorption of proteins may severely limit the amount of free unbound proteins that is avail-
able for release. Another major consequence of adsorption may be the surface-induced changes in
the three-dimensional (3-D) structure of proteins that could result in loss of biological activity of
proteins [53]. This loss of activity may also evoke some immune response in some cases, which in
turn can be a major drawback. Several studies have indicated the loss of bioactivity of insulin and
salmon calcitonin following the encapsulation onto the biodegradable matrix [52,54].
Another major concern is the in vivo fate of these nanoparticles following their uptake by the
Peyer's patches. A major aspect is that the exact mechanism of particle uptake is still unclear.
A probable mechanism is that the particles absorbed through the Peyer's patches reaches mesenteric
duct fi rst and through cystema chyli and thoracic duct reaches bloodstream. A major obstacle is the
“RES clearance” of polymeric systems in the body [55]. Particulate carriers in the blood streams
may be identifi ed by a group of scavenger cells known as RES, which are located largely in organs
such as liver, spleen, lung, and the like. Most colloidal carriers are rapidly removed from the circu-
lation by phagocytic cells in liver and spleen. The recognition of particles by RES is mediated by
interactions of blood components with the artifi cial surface of the carriers (opsonization) leading
to activation of the complement system. Moreover, the increase in hydrophobicity or introduction
of cationic charges signifi cantly enhances the clearance of these particles from the blood streams
[56]. However, these features are some of the prerequisites for the uptake of particles from the GIT.
Hence optimization of surface properties or charge without compromising the properties remains a
major challenge in this area. A recent area of concern is the long-term effects of these particles on
the human body, and more intense investigations are required in this direction.
Linear polyesters of lactides and glycolides, poly(alkyl cyanoacrylates), polyanhydrides, poly-
phosphazenes are some of the polymers commonly used in the development of polymeric particles.
 
Search WWH ::




Custom Search