Biomedical Engineering Reference
In-Depth Information
vitro cellular uptake efficiency as compared to the free drug (Hu et al. 2013). It can be
studied using various fluorescent markers, such as 6-coumarin, rhodamin B, floures-
cein Isothiocyanate, Quantum Dots and so on. Yuan et al. used chemical conjugated
fluorescent dye (ODA-FITC) to explain the cellular uptake mechanism of paclitaxel
encapsulated SLN in A549 cells. It was observed after a thorough study that the nano-
particles get entered into the cells via endocytosis in which the particles adhere to the
cell membrane and internalized in a vesicle. This vesicle further detaches from the
membrane and release to the cytoplasm (Yuan et al. 2008; Acha et al. 2011).
Generally endocytosis can be categorized as phagocytosis and pinocytosis where
pinocytosis can further be classified as clathrin mediated, caveolae mediated, clath-
rin and caveolae independent endocytosis and macropinocytosis (Sahay et al. 2011).
Different routes of internalization for nanoparticles are confirmed using mecha-
nism inhibition approach. For instance, as it is known that endocytosis is an energy
dependent process, Martinsa et al. showed that when cells treated with R123-SLN
were incubated at 4 °C instead of 37 °C, rate of endocytosis reduced as well as the
level of fluorescent intensity inside the cultured cells decreased drastically as com-
pared to cells grown at standard conditions. In addition to this, the main route of
internalization was found to be clathrin dependent (Martinsa et al. 2012). Ningning
et al. observed that size, shape and surface functionalization of nanoparticles greatly
influence the mechanism of cellular entry (Ma et al. 2013). For last some years, the
surface of drug carriers has been modified using PEG (polyethylene glycol) to ren-
der particles hydrophilic and to improve the internalization efficiency as it possess
high solubility in cell membranes. Also, pegylated SLNs show enhanced mucous
penetrating ability in addition to high permeation across the cell membrane but non-
specific uptake is shown by PEGylated SLN (Yuan et al. 2013).
For receptor-mediated endocytosis, the surface of SLN is decorated with
ligands (e.g. folic acid) to accumulate drug loaded SLN at the target site. Mulik
et al. reported the enhanced intracellular uptake via receptor mediated endocytosis
when SLN was conjugated with transferrin (Tf-SLN) as cancer cells overexpress
the transferrin receptors (Mulik et al. 2012).
Cellular uptake of SLN was found to be time and lipid composition dependent. It
also depends upon the melting point of the lipid used to make SLN. For example, four
SLNs were prepared using glycerol tristearate, monostearin, stearic acid and ATO 888.
As the melting point of monostearin was lowest, it showed higher uptake efficiency
as compared to stearic acid SLN and ATO888 SLN. According to the reason given,
glycerol tristearate SLN should have the lowest internalization ability but it showed
the fastest uptake. This could be due to smallest size of tristearate SLN explaining the
dependence of cellular uptake on the size of the particles (Yuan et al. 2008).
6.7 Drug Delivery Routes
The drugs can be administered via various routes inside the body and different
routes may have different impact on the in vivo fate of the drugs as well as on the
carrier. As SLN are composed of lipids, a variety of enzymes present in various
