piperine-mediated inhibition of mitogen-activated protein kinases also contributes to
the failure of DCs to migrate in response to CCL21 since CCR7-induced chemotaxis
of DCs involves the activation of extracellular signal-regulated kinase and p38
mitogen-activated protein kinase (Riol-Blanco et al. 2005). Antigen-specific stimulation of OVA323–339-specific CD4+ T-cells with piperine-treated DCs resulted in
decreased production of IL-2 and IFN-c, indicating that T helper cells were directed
away from the Th1 phenotype that is typically induced by DCs differentiated with
granulocyte–macrophage colony-stimulating factor (Eksioglu et al. 2007). In contrast, there was no reduction in CD4+ T-cell production of IL-4 and IL-17, suggesting
that T helper cells had not been alternatively directed to a Th2 or Th17 phenotype.
A similar decrease in CD4+ T-cell synthesis of IFN-c with no change in IL-4 production occurs when CD4+ T-cells are stimulated with DCs that were treated with
dexamethasone prior to LPS maturation (Matyszak et al. 2000). Interestingly, multiple restipulation of CD4+ T-cells with dexamethasone-treated DCs resulted in the
selective induction of T regulatory cells. Although we did not determine whether
piperine-treated DCs also induced T regulatory cells, such an outcome seems unlikely
given that T regulatory cells require IL-2 for their development and function (Burchill
et al. 2007; de la Rosa et al. 2004). We also observed that the in vivo proliferation of
OVA323–339-specific CD4+ T-cells was virtually ablated when piperine-treated
DCs were used as antigen-presenting cells. This profound inhibitory effect on
CD4+ T-cell activation was likely due to reduced migration of piperine-treated DCs
to lymph nodes and impaired interactions with CD4+ T-cells as a result of decreased
DC expression of CD40 and MHC II molecules (Rodgers et al. 2016).
22.24 Piperine-Laden Nanoparticles with Increased
Dissolving and Improved Bioavailability
for Controlling Epilepsy
The reduction of size is a regular exercise to enhance the drug solubility by raising
the surface area to mass quotient, altering particle curvature that institute defects
into crystal lattice (Williams et al. 2013). The solubility and dissolution of piperine
have been improved by several formulation techniques, such as solid dispersion
with hot melt extrusion technology, Tween 80 coated solid lipid nanoparticles and
microemulsion with self-emulsifying drug delivery system (Ashour et al. 2016;
Elnaggar et al. 2015; Shao et al. 2015). However, none of these formulations have
been verified to confirm its anti-epileptic effect. Although nanoprecipitation method
has been used to develop a piperine and curcumin co-loaded nanoparticle preparation before, the feasibility for nanoprecipitation with piperine only and its subsequent effect for epilepsy control have never been attempted (Moorthi et al. 2012).
In the study, they developed a nanosized formulation of piperine by nanoprecipitation method to enhance its solubility, dissolution, and improve systemic exposure
of piperine after oral administration, which is a noninvasive route that is suitable for
780
N. Sachan et al.
the failure of DCs to migrate in response to CCL21 since CCR7-induced chemotaxis
of DCs involves the activation of extracellular signal-regulated kinase and p38
mitogen-activated protein kinase (Riol-Blanco et al. 2005). Antigen-specific stimulation of OVA323–339-specific CD4+ T-cells with piperine-treated DCs resulted in
decreased production of IL-2 and IFN-c, indicating that T helper cells were directed
away from the Th1 phenotype that is typically induced by DCs differentiated with
granulocyte–macrophage colony-stimulating factor (Eksioglu et al. 2007). In contrast, there was no reduction in CD4+ T-cell production of IL-4 and IL-17, suggesting
that T helper cells had not been alternatively directed to a Th2 or Th17 phenotype.
A similar decrease in CD4+ T-cell synthesis of IFN-c with no change in IL-4 production occurs when CD4+ T-cells are stimulated with DCs that were treated with
dexamethasone prior to LPS maturation (Matyszak et al. 2000). Interestingly, multiple restipulation of CD4+ T-cells with dexamethasone-treated DCs resulted in the
selective induction of T regulatory cells. Although we did not determine whether
piperine-treated DCs also induced T regulatory cells, such an outcome seems unlikely
given that T regulatory cells require IL-2 for their development and function (Burchill
et al. 2007; de la Rosa et al. 2004). We also observed that the in vivo proliferation of
OVA323–339-specific CD4+ T-cells was virtually ablated when piperine-treated
DCs were used as antigen-presenting cells. This profound inhibitory effect on
CD4+ T-cell activation was likely due to reduced migration of piperine-treated DCs
to lymph nodes and impaired interactions with CD4+ T-cells as a result of decreased
DC expression of CD40 and MHC II molecules (Rodgers et al. 2016).
22.24 Piperine-Laden Nanoparticles with Increased
Dissolving and Improved Bioavailability
for Controlling Epilepsy
The reduction of size is a regular exercise to enhance the drug solubility by raising
the surface area to mass quotient, altering particle curvature that institute defects
into crystal lattice (Williams et al. 2013). The solubility and dissolution of piperine
have been improved by several formulation techniques, such as solid dispersion
with hot melt extrusion technology, Tween 80 coated solid lipid nanoparticles and
microemulsion with self-emulsifying drug delivery system (Ashour et al. 2016;
Elnaggar et al. 2015; Shao et al. 2015). However, none of these formulations have
been verified to confirm its anti-epileptic effect. Although nanoprecipitation method
has been used to develop a piperine and curcumin co-loaded nanoparticle preparation before, the feasibility for nanoprecipitation with piperine only and its subsequent effect for epilepsy control have never been attempted (Moorthi et al. 2012).
In the study, they developed a nanosized formulation of piperine by nanoprecipitation method to enhance its solubility, dissolution, and improve systemic exposure
of piperine after oral administration, which is a noninvasive route that is suitable for
780
N. Sachan et al.