Drug Administration (FDA) revealed that about 40% of the approved molecules are
either natural compounds or inspired by them and, from these, 74% are indicated
for anticancer therapy (Seca and Pinto 2018). Still, it has been reported that about
95% of the world’s biodiversity are yet to be systemically investigated for their
pharmacological activity and only 15% have been evaluated phytochemically
(Atanasov et al. 2015; David et al. 2015). The current global scenario and the urgent
need for effective therapy to treat chronic as well as infectious diseases including
cancer and HIV implied that natural products will continue to play a pivotal role in
drug discovery and development processes (Cragg and Newman 2013).
Although natural products are considered to be safe and their bioactive phytochemicals exhibit excellent pharmacological activities in vitro, they often failed to
translate this into clinical or therapeutic effects in vivo. The major problems
associated with bioactive phytochemicals include their low oral absorption and
rapid systemic clearance which ultimately lowers their bioavailability and therapeutic efficacy in vivo (Kumar et al. 2010; Rein et al. 2012). For instance, oral
administration of curcumin at 500 mg/kg in Sprague-Dawley rats produced maximum plasma concentration (C max ) of 0.06 ± 0.01 µg/ml after 41.7 ± 5.4 min
(Yang et al. 2007), while in healthy human volunteers, curcumin was detected in
the serum only when it was administered orally at a dose higher than 8 g (Lao et al.
2006). Similarly, other potent bioactive compounds such as quercetin (Almeida
et al. 2018; Kasikci and Bagdatlioglu 2016), paclitaxel (Malingre et al. 2001;
Tiwari and Amiji 2006), and ellagic acid (Bala et al. 2006; Lei et al. 2003) also
produced extremely low oral bioavailability eventually resulting in suboptimal oral
therapy in vivo. Predominant factors that led to the poor oral absorption of these
natural bioactive compounds are their eminently low aqueous solubility, poor
dispersibility, and bioaccessibility which are the prerequisites for absorption
through the gastrointestinal (GI) tract. For example, the maximum solubility of
curcumin in aqueous buffer pH 5.0 is only 11 ng/ml (Ma et al. 2019) and the
aqueous solubility of ellagic acid is about 9.7 µg/ml (Alfei et al. 2019). In addition,
instability of various bioactive compounds on exposure to environmental factors
such as pH, enzymes, light, heat, oxygen, and moisture may also contribute to their
degradation in vitro and in vivo (Bohn et al. 2015; Islam Shishir et al. 2018).
Moreover, biological factors including permeability of the intestinal epithelium, the
presence of efflux transporters such as P-glycoprotein and the induction or inhibition of metabolizing enzymes may also serve as barriers to oral bioavailability of
several bioactive compounds (Chu et al. 2008; Ma et al. 2019; Xie et al. 2011).
Overcoming these challenges has become one of the most important focuses of the
current research on improving the oral bioavailability of bioactive compounds.
Techniques such as micronization (Aguiar et al. 2018) or nanonization (Aditya et al.
2019; Borhan et al. 2014) to reduce the particle size, co-administration of phytochemicals with bio-enhancers such as piperine (Gorgani et al. 2017), micro- and
nanoencapsulation with different types of coating materials (Dias et al. 2017;
Ezhilarasi et al. 2013) are some of the approaches designed to achieve the oral
bioavailability enhancement of bioactive compounds.
20 Encapsulation of Bioactive Compound and Its Therapeutic Potential
689
either natural compounds or inspired by them and, from these, 74% are indicated
for anticancer therapy (Seca and Pinto 2018). Still, it has been reported that about
95% of the world’s biodiversity are yet to be systemically investigated for their
pharmacological activity and only 15% have been evaluated phytochemically
(Atanasov et al. 2015; David et al. 2015). The current global scenario and the urgent
need for effective therapy to treat chronic as well as infectious diseases including
cancer and HIV implied that natural products will continue to play a pivotal role in
drug discovery and development processes (Cragg and Newman 2013).
Although natural products are considered to be safe and their bioactive phytochemicals exhibit excellent pharmacological activities in vitro, they often failed to
translate this into clinical or therapeutic effects in vivo. The major problems
associated with bioactive phytochemicals include their low oral absorption and
rapid systemic clearance which ultimately lowers their bioavailability and therapeutic efficacy in vivo (Kumar et al. 2010; Rein et al. 2012). For instance, oral
administration of curcumin at 500 mg/kg in Sprague-Dawley rats produced maximum plasma concentration (C max ) of 0.06 ± 0.01 µg/ml after 41.7 ± 5.4 min
(Yang et al. 2007), while in healthy human volunteers, curcumin was detected in
the serum only when it was administered orally at a dose higher than 8 g (Lao et al.
2006). Similarly, other potent bioactive compounds such as quercetin (Almeida
et al. 2018; Kasikci and Bagdatlioglu 2016), paclitaxel (Malingre et al. 2001;
Tiwari and Amiji 2006), and ellagic acid (Bala et al. 2006; Lei et al. 2003) also
produced extremely low oral bioavailability eventually resulting in suboptimal oral
therapy in vivo. Predominant factors that led to the poor oral absorption of these
natural bioactive compounds are their eminently low aqueous solubility, poor
dispersibility, and bioaccessibility which are the prerequisites for absorption
through the gastrointestinal (GI) tract. For example, the maximum solubility of
curcumin in aqueous buffer pH 5.0 is only 11 ng/ml (Ma et al. 2019) and the
aqueous solubility of ellagic acid is about 9.7 µg/ml (Alfei et al. 2019). In addition,
instability of various bioactive compounds on exposure to environmental factors
such as pH, enzymes, light, heat, oxygen, and moisture may also contribute to their
degradation in vitro and in vivo (Bohn et al. 2015; Islam Shishir et al. 2018).
Moreover, biological factors including permeability of the intestinal epithelium, the
presence of efflux transporters such as P-glycoprotein and the induction or inhibition of metabolizing enzymes may also serve as barriers to oral bioavailability of
several bioactive compounds (Chu et al. 2008; Ma et al. 2019; Xie et al. 2011).
Overcoming these challenges has become one of the most important focuses of the
current research on improving the oral bioavailability of bioactive compounds.
Techniques such as micronization (Aguiar et al. 2018) or nanonization (Aditya et al.
2019; Borhan et al. 2014) to reduce the particle size, co-administration of phytochemicals with bio-enhancers such as piperine (Gorgani et al. 2017), micro- and
nanoencapsulation with different types of coating materials (Dias et al. 2017;
Ezhilarasi et al. 2013) are some of the approaches designed to achieve the oral
bioavailability enhancement of bioactive compounds.
20 Encapsulation of Bioactive Compound and Its Therapeutic Potential
689