Unlike any other proteins used in drug delivery, milk protein casein is not
sensitive to temperature or mild pH changes. In a study investigating the stability
of casein nanocarriers over a broad pH range of 6.5–12, it was noted that pH
changes do not alter the properties of these nanocarriers [115]. Casein is
stable up to 70
C, beyond which it shows considerable degradation [75]. With
long-term lyophilized storage, casein itself acts as a cryoprotectant. Celecoxibloaded β-casein nanoparticles were cryopreserved for 6 months and easily
re-suspended on rehydration [116]. Caseins are also well known for protecting
the payload even under harsh environments, for example, its effective protection of
vitamin D2 and 1,4-dihydroxyanthraquinone (DHA) against UV-induced degradation [117].
2.4 Circulation of Nanocarriers
The activity of a drug in the host is best measured in terms of their plasma half life
(t 1/2 ) and its plasma concentration. Many drugs have very low t 1/2 values, once
exposed to the host environment because they are metabolized, degraded, or cleared
by the local system, thereby limiting their clinical activity to a very short duration,
sometimes as low as minutes. Entrapping such fast-clearing drugs within
nanocarriers helps to confine the drug in its active state within the matrix, and
sustained release from these carriers ensures clinical activity for longer durations.
However, a major obstacle in the development of polymeric nanoparticles as
effective drug delivery carriers is their rapid clearance from blood. Blood circulation residence time, which ultimately leads to a high therapeutic index, is one of the
important factors that determine the clinical success of a pharmaceutical formulation. Surface modification or functionalization of nanoparticles helps in increasing
the mean residence time of particles in blood by imparting “stealth” (shielding of
the particle surface with a coating material) or sterically stabilized properties to
nanoparticles [106].
Carbohydrates and proteins could be potential candidates for successful drug
delivery due to their abundance of functional groups that can act as ligands for
surface modification. Such surface-modified nanocarriers would block the serum
proteins (opsonins) from binding to them and remain camouflaged to phagocytic
cells, thereby reducing their rapid clearance from the blood stream. Delays in
opsonization can be achieved either through the adsorption of polymers or
surfactants on nanocarrier surfaces via covalent or non-covalent attachment of
molecules. Although one of the most widely utilized strategies is adsorption or
grafting of PEG molecules on the nanocarrier surface, appropriate surface modification of the nanocarriers using carbohydrates can also help evade opsonization
[118].
In addition to surface modification, particle size is another key factor that
affects the circulation time of nanocarriers. The smaller the particle size, the
lesser will be the protein adsorption and slower the clearance. To demonstrate
Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems. . .
255
sensitive to temperature or mild pH changes. In a study investigating the stability
of casein nanocarriers over a broad pH range of 6.5–12, it was noted that pH
changes do not alter the properties of these nanocarriers [115]. Casein is
stable up to 70
C, beyond which it shows considerable degradation [75]. With
long-term lyophilized storage, casein itself acts as a cryoprotectant. Celecoxibloaded β-casein nanoparticles were cryopreserved for 6 months and easily
re-suspended on rehydration [116]. Caseins are also well known for protecting
the payload even under harsh environments, for example, its effective protection of
vitamin D2 and 1,4-dihydroxyanthraquinone (DHA) against UV-induced degradation [117].
2.4 Circulation of Nanocarriers
The activity of a drug in the host is best measured in terms of their plasma half life
(t 1/2 ) and its plasma concentration. Many drugs have very low t 1/2 values, once
exposed to the host environment because they are metabolized, degraded, or cleared
by the local system, thereby limiting their clinical activity to a very short duration,
sometimes as low as minutes. Entrapping such fast-clearing drugs within
nanocarriers helps to confine the drug in its active state within the matrix, and
sustained release from these carriers ensures clinical activity for longer durations.
However, a major obstacle in the development of polymeric nanoparticles as
effective drug delivery carriers is their rapid clearance from blood. Blood circulation residence time, which ultimately leads to a high therapeutic index, is one of the
important factors that determine the clinical success of a pharmaceutical formulation. Surface modification or functionalization of nanoparticles helps in increasing
the mean residence time of particles in blood by imparting “stealth” (shielding of
the particle surface with a coating material) or sterically stabilized properties to
nanoparticles [106].
Carbohydrates and proteins could be potential candidates for successful drug
delivery due to their abundance of functional groups that can act as ligands for
surface modification. Such surface-modified nanocarriers would block the serum
proteins (opsonins) from binding to them and remain camouflaged to phagocytic
cells, thereby reducing their rapid clearance from the blood stream. Delays in
opsonization can be achieved either through the adsorption of polymers or
surfactants on nanocarrier surfaces via covalent or non-covalent attachment of
molecules. Although one of the most widely utilized strategies is adsorption or
grafting of PEG molecules on the nanocarrier surface, appropriate surface modification of the nanocarriers using carbohydrates can also help evade opsonization
[118].
In addition to surface modification, particle size is another key factor that
affects the circulation time of nanocarriers. The smaller the particle size, the
lesser will be the protein adsorption and slower the clearance. To demonstrate
Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems. . .
255