this fact, poly (cyanoacrylate-co-n-hexadecyl)cyanoacrylate (PHDCA) particles
with different sizes, i.e., small (<100 nm), medium (100–200 nm) and large
(>200 nm), were incubated with serum proteins for 2 h yielding protein adsorption values of 6%, 23%, and 34%, respectively. A significant correlation between
size and protein adsorption was clearly apparent. This was further confirmed by
the particle uptake in murine macrophages and its blood clearance kinetics. The
experiments helped to conclude that particles with appropriate surface modification and size less than 100 nm showed less protein adsorption, rendering longer
circulation time. Apart from hydrophilic coatings and size, surface charge also
plays a significant role in the clearance of nanoparticles from circulation. Nonspecific cellular internalization and protein adsorption during circulation can be
affected by altering the surface charge of nanocarriers. The particles with higher
positive charge are prone to have a rapid uptake by phagocytic cells, as compared
to negative or neutral particles, resulting in shorter blood circulation half-lives
[13, 119].
2.4.1 Circulation of Carbohydrates
In addition to being a promising matrix for drug delivery, carbohydrates also offer
methods for improving the blood residence time of nanocarriers through glycosylation [86]. Glycosylated nanocarriers have the additional attributes of improving
the pharmacokinetic profile of drugs, providing carrier stabilization as well as
receptor-targeted drug delivery.
Linear dextrans that are frequently used as plasma expanders in medicine can
remain in the systemic circulation for extended periods of time that are proportional
to their molecular weights. The steric brushes of the dextran macromolecules have
shown enhanced stability with reduced protein adsorption for various drugs, nanoparticles (iron oxide, liposomes), etc. [120, 121]. A bacterial exopolysaccharide,
i.e., pullulan, which forms conjugates with cholesterol has also been reported to
confer protection to liposome surfaces and reduce macrophage uptake in vivo [122].
This apart, carbohydrate moieties such as mannose, galactose, etc. have been
extensively explored for their potential use as active targeting ligands that bind
specifically to cell surface receptors and deliver therapeutic agents at the desired
site [123–125].
A combinatorial coating of PEG and cationic WSC, on PLA nanoparticles, has
yielded greatly prolonged circulation time for the nanocarriers in vivo. In contrast to
PLA nanoparticles treated with PEG or WSC alone, PEG and WSC synergistically
provided a strong inhibition of macrophage uptake and extended the circulation
half-life up to 63.5 h, with concomitant reduced liver sequestration. This t 1/2 value
was much longer than that of control PEG/PVA nanoparticles (1.1 h) as well as that
of PLA nanoparticles stabilized with PEG/CPCTS (anionic N-carboxy propionyl
256
D. Narayanan et al.
with different sizes, i.e., small (<100 nm), medium (100–200 nm) and large
(>200 nm), were incubated with serum proteins for 2 h yielding protein adsorption values of 6%, 23%, and 34%, respectively. A significant correlation between
size and protein adsorption was clearly apparent. This was further confirmed by
the particle uptake in murine macrophages and its blood clearance kinetics. The
experiments helped to conclude that particles with appropriate surface modification and size less than 100 nm showed less protein adsorption, rendering longer
circulation time. Apart from hydrophilic coatings and size, surface charge also
plays a significant role in the clearance of nanoparticles from circulation. Nonspecific cellular internalization and protein adsorption during circulation can be
affected by altering the surface charge of nanocarriers. The particles with higher
positive charge are prone to have a rapid uptake by phagocytic cells, as compared
to negative or neutral particles, resulting in shorter blood circulation half-lives
[13, 119].
2.4.1 Circulation of Carbohydrates
In addition to being a promising matrix for drug delivery, carbohydrates also offer
methods for improving the blood residence time of nanocarriers through glycosylation [86]. Glycosylated nanocarriers have the additional attributes of improving
the pharmacokinetic profile of drugs, providing carrier stabilization as well as
receptor-targeted drug delivery.
Linear dextrans that are frequently used as plasma expanders in medicine can
remain in the systemic circulation for extended periods of time that are proportional
to their molecular weights. The steric brushes of the dextran macromolecules have
shown enhanced stability with reduced protein adsorption for various drugs, nanoparticles (iron oxide, liposomes), etc. [120, 121]. A bacterial exopolysaccharide,
i.e., pullulan, which forms conjugates with cholesterol has also been reported to
confer protection to liposome surfaces and reduce macrophage uptake in vivo [122].
This apart, carbohydrate moieties such as mannose, galactose, etc. have been
extensively explored for their potential use as active targeting ligands that bind
specifically to cell surface receptors and deliver therapeutic agents at the desired
site [123–125].
A combinatorial coating of PEG and cationic WSC, on PLA nanoparticles, has
yielded greatly prolonged circulation time for the nanocarriers in vivo. In contrast to
PLA nanoparticles treated with PEG or WSC alone, PEG and WSC synergistically
provided a strong inhibition of macrophage uptake and extended the circulation
half-life up to 63.5 h, with concomitant reduced liver sequestration. This t 1/2 value
was much longer than that of control PEG/PVA nanoparticles (1.1 h) as well as that
of PLA nanoparticles stabilized with PEG/CPCTS (anionic N-carboxy propionyl
256
D. Narayanan et al.