Biomedical Engineering Reference
In-Depth Information
to 3 μm revealed that the maximal absorption occurred with particles ranging from 50 to 100 nm in
diameter, with particles above 1 μm being trapped in the Peyer's patches. Attempts were further made
to study the mechanism responsible for the process and to explore their possible application in drug
delivery [37]. It is proposed that M-cells of Peyer's patches are largely responsible for the uptake of
these particles [38].
Gut-associated lymphoid tissue (GALT) consists of lymphoid follicles arranged in single or in
clusters to form distinct structures called Peyer's patches. The epithelium overlying the follicle is
called the follicle-associated epithelium (FAE). This FAE contains specialized antigen sampling cells
known as M-cells, which have unique structural features with sparse irregular microvilli on the apical
side. In addition, they possess a basolateral cytoplasmic invagination that creates a pocket containing
one or more lymphocytes and possibly macrophages. M-cells are thought to sample and transport
antigens from the gut lumen to the underlying lymphoid cells and may elicit an immune response.
While acting in this immunological surveillance role, it has been suggested that the M-cells absorb
particles and consequently may be exploited for the delivery of therapeutic peptides and proteins or
vaccines [39-41].
Nanoparticles administered orally are absorbed, not only by way of the membranous epithelial
cells (M-cells) of the Peyer's patches, but also by the much more numerous gut enterocytes. The
absorption of the Particles is described as crossing either at the level of Peyer's patches or through
the enterocyte layer. Usually particles absorbed through the Peyer's patches end up in the lymph
and are carried through the mesenteric lymph vessels into the thoracic duct, which are further
cleared into the bloodstream. Lymph from the intestinal lymphatic system drains through the tho-
racic lymph duct into the left internal jugular vein and then to the systemic circulation. Thus, the
transport of drug through the intestinal lymphatic system may increase the percentage of drug that
can gain access to the systemic circulation [42]. In addition, the process of intestinal lymphatic
drug transport often continues over time periods longer than typically observed for drug absorption
through the portal vein. Consequently, drug transport through the lymph may be utilized to prolong
the time course of drug delivery to the systemic circulation.
The uptake is preceded by the interaction of the particles with the cell surface. Therefore, the
nature of the polymer, mainly the hydrophobic or hydrophilic balance and the surface charge, will
affect the uptake process to a large extent [28]. Physicochemical properties of particles govern their
rate of uptake from the intestinal tract. The two main deciding factors are the size and the nature of
the polymer used to make the particles.
Many studies regarding the size effects of nanoparticles absorption by intestinal epithelia have
been performed using poly(styrene) standard particle suspensions. Particles with mean diameters
of 50 and 100 nm showed a higher uptake in the rat intestine than larger particles [44]. The uptake
of the nanoparticles was followed by their appearance in the systemic circulation and distribution
to different tissues. After administration of equivalent doses of 33% of the 50 nm and 26% of the
100 nm, nanoparticles were detected in the intestinal mucosa and GALT [45]. In the case of 500 nm
nanoparticles, only 10% were localized in intestinal tissues. Nanoparticles with size greater than
1 μm in diameter yielded only little uptake and had exclusive localization in Peyer's patches. Similarly
poly(D, L-lactic-co-glycolide) (PLGA) nanoparticles with size 100 nm were uptaken from intestine,
and effi ciency was higher when compared with larger particles. It was clear from these experiments
that the intestinal uptake of particles largely depends on the size [45-47].
Another major factor affecting the particle uptake is the nature of the material used to prepare
the particles. Uptake of nanoparticles prepared from hydrophobic polymers seems to be higher than
that from particles with more hydrophilic surfaces [32]. Microspheres composed of polystyrene,
poly(methylmethacrylate), poly(hydroxybutyrate), poly(d,l-lactide), poly(l-lactide) and poly(d,l-
lactide-
co
-glycolide) were absorbed into the Peyer's patches of the small intestine, whereas those
composed of ethyl cellulose, cellulose acetate hydrogen phthalate, and cellulose triacetate were
not absorbed. Residual poly(vinyl alcohol) in the surface of PLGA nanoparticles signifi cantly
reduced the intercellular uptake, in spite of the smaller particle size [48]. Similarly, poloxamer
