chitosan sodium) (7.1 h), thereby proving the effect of surface stabilization in
developing long-circulating drug delivery carriers [85, 104, 126].
2.4.2 Circulation of Proteins
Long-term retention of protein nanoparticles in host blood circulation is essentially
governed by the surface properties, which makes them vulnerable to macrophage
uptake, enzymatic degradation, and renal or hepatic clearance. However, by appropriate surface modification and targeting strategies, such uptake and clearance can
be alleviated to a certain limit.
In an attempt to demonstrate this, Amiji et al. prepared PEG-modified gelatin
nanoparticles and observed that modification of gelatin using hydrophilic PEG
molecules helped to effectively evade proteolytic enzymes by steric repulsion
[105]. The biodistribution studies using these PEGylated nanoparticles revealed
their long circulation, with a half life of 15–39 h [127]. The targetability of PEGcoated gelatin nanocarriers was also assessed in a different study, wherein the
surface-modified nanoparticles were found to have the capacity to accumulate at
the tumor site and remain at this site up to 12 h [128]. A significant prolongation in
blood circulation of ibuprofen sodium (IbS)-loaded gelatin nanoparticles was
observed upon PEGylation, providing a sustained release of IbS for ~96 h, thereby
improving the bioavailability and pharmacokinetics of the drug when compared to
bare IbS and non-PEGylated nanoparticles (Narayanan et al. 2012, unpublished).
Albumin is a natural long-circulating polymer with a plasma half life of 19 days
[7, 48, 110]. In a recent study, the plasma half -life of cisplatin was found to be
enhanced from 65 min to 24 h, when entrapped within folate-conjugated albumin
nanoparticles [129]. Chemical conjugation of PEG to albumin also increases its
circulation capabilities at least fivefold, reduces its immunogenicity, and augments
the enhanced permeability and retention effect and thereby tumor localization
[130]. In another study, PEGylated albumin nanocarriers ensured a slower release
of Rose Bengal, even in the presence of proteolytic enzymes, suggesting the effect
of steric hindrance offered by PEG [131]. These examples suggest that surface
modification of protein nanocarriers either by polymers like PEG, PLL, and PVA or
by targeting ligands establishes a barrier between the carrier and its surroundings,
thus reducing its chances of detection by the immune system or by enzymes,
thereby rendering a longer circulation and targetability for the nanoparticles.
3 Formulational Approach
Hydrophilic and hydrophobic drugs can be encapsulated within carbohydrate or
protein nanocarriers in several ways [16, 35, 86, 87]. However, the selection of a
specific route of synthesis depends upon various requirements including particle
Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems. . .
257
developing long-circulating drug delivery carriers [85, 104, 126].
2.4.2 Circulation of Proteins
Long-term retention of protein nanoparticles in host blood circulation is essentially
governed by the surface properties, which makes them vulnerable to macrophage
uptake, enzymatic degradation, and renal or hepatic clearance. However, by appropriate surface modification and targeting strategies, such uptake and clearance can
be alleviated to a certain limit.
In an attempt to demonstrate this, Amiji et al. prepared PEG-modified gelatin
nanoparticles and observed that modification of gelatin using hydrophilic PEG
molecules helped to effectively evade proteolytic enzymes by steric repulsion
[105]. The biodistribution studies using these PEGylated nanoparticles revealed
their long circulation, with a half life of 15–39 h [127]. The targetability of PEGcoated gelatin nanocarriers was also assessed in a different study, wherein the
surface-modified nanoparticles were found to have the capacity to accumulate at
the tumor site and remain at this site up to 12 h [128]. A significant prolongation in
blood circulation of ibuprofen sodium (IbS)-loaded gelatin nanoparticles was
observed upon PEGylation, providing a sustained release of IbS for ~96 h, thereby
improving the bioavailability and pharmacokinetics of the drug when compared to
bare IbS and non-PEGylated nanoparticles (Narayanan et al. 2012, unpublished).
Albumin is a natural long-circulating polymer with a plasma half life of 19 days
[7, 48, 110]. In a recent study, the plasma half -life of cisplatin was found to be
enhanced from 65 min to 24 h, when entrapped within folate-conjugated albumin
nanoparticles [129]. Chemical conjugation of PEG to albumin also increases its
circulation capabilities at least fivefold, reduces its immunogenicity, and augments
the enhanced permeability and retention effect and thereby tumor localization
[130]. In another study, PEGylated albumin nanocarriers ensured a slower release
of Rose Bengal, even in the presence of proteolytic enzymes, suggesting the effect
of steric hindrance offered by PEG [131]. These examples suggest that surface
modification of protein nanocarriers either by polymers like PEG, PLL, and PVA or
by targeting ligands establishes a barrier between the carrier and its surroundings,
thus reducing its chances of detection by the immune system or by enzymes,
thereby rendering a longer circulation and targetability for the nanoparticles.
3 Formulational Approach
Hydrophilic and hydrophobic drugs can be encapsulated within carbohydrate or
protein nanocarriers in several ways [16, 35, 86, 87]. However, the selection of a
specific route of synthesis depends upon various requirements including particle
Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems. . .
257