*4.4.1 Anti-cancer drug delivery*

Chemotherapeutic APIs usually exhibit low bioavailability following oral administration. Several studies have investigated chitosan-based NP as a possible delivery system to address this issue. For example, doxorubicin (Dox), broadly employed to treat breast, bladder and other cancers, is typically delivered intravenously. The oral bioavailability of Dox is low due to efflux transporter P-glycoprotein, which identifies Dox as a substrate, restraining its cellular uptake [105]. In 2013, Feng et al. developed chitosan/o-carboxymethyl chitosan (CS/CMCS) NP as a pH responsive carrier for the oral delivery of Dox. They investigated the bioavailability of orally administered Dox-CS/CMCS NP and free Dox drug on Sprague–Dawley rats. Negligible Dox was detected in plasma after the oral dosage of free Dox, representing its poor absorption. On the other hand, 2.3-folds increase in plasma concentration of Dox was registered after an oral dose of Dox-CS/CMCS NP. Moreover, accumulation of Dox in the liver, spleen and lungs were demonstrated in rats treated with oral Dox- CS/CMCS NP, as opposed to DoX solution which was more concentrated in the kidneys. They concluded that the NP matrix improved the intestinal absorption of Dox and thus improved oral bioavailability [106].

**39**

*Gastrointestinal Delivery of APIs from Chitosan Nanoparticles*

potential candidate for colon cancer treatment [108].

therapeutic antimicrobial when administered orally.

*4.4.3 Polyphenolic compounds delivery*

Gemcitabine (Gem) is a widely prescribed anticancer agent used in pancreatic, lung and advanced colon cancer. Oral administration of Gem results in low oral bioavailability, high first-pass clearance gastrointestinal toxicity, such as nausea, vomiting and diarrhoea [107]. Hosseinzadeh et al. synthesised and characterised chitosan/Pluronic® F-127 (Gem-Chi/PF) NP in oral delivery of Gem for the treatment of colon cancer. *In vitro* studies showed that the NP presented enhanced cytotoxicity effects against HT-29 cell line and concluded that Gem-Chi/PF NP is a

Chitosan impedes the growth of bacteria, fungi, and yeast [109]. It exhibits potential antimicrobial properties at pH below 6.0 because of the positively

chitosan derived NP integrate with bacterial DNA, impeding mRNA synthesis.

negatively-charged cell wall in microorganisms and subsequently amend cell permeability [110]. Alqahtani et al. formulated chitosan NP from high and low molecular weight variants to encapsulate the non-antibiotic diclofenac sodium (DIC). The antibacterial properties of NP from low and high molecular weight of chitosan on *Staphylococcus aureus* and *Bacillus subtilis* was significantly higher than from DIC alone. The antibacterial activity of chitosan was higher from the high molecular weight chitosan at pH = 5.5 [111]. In another *in vitro* study, Qi et al., investigated the antibacterial activity of chitosan NP and copper-loaded chitosan NP against various microorganisms (*E. coli, S. choleraesuis, S. typhimurium and S. aureus*). The antibacterial activity of chitosan NP and copper-loaded chitosan NP were significantly higher than from chitosan and doxycycline alone. Furthermore, copper-loaded NP indicated higher antibacterial activity against microorganism compared to chitosan NP void of copper. They concluded that this is due to the higher surface charge density of copper-loaded NP that improves the affinity of the cargo with the negatively charged bacteria membrane. Clearly, the antimicrobial property of chitosan is demonstrable and may augment the antibacterial effects of

Secondary plant metabolites in the form of polyphenolic compounds have gained wide attention by scientists due to their wide spectrum of pharmacological activities, including antioxidant, antimicrobial and anticancer properties. Most however suffer from poor systemic bioavailability following oral administration due to low solubility and susceptibility to GI degradation. To overcome this constraint, chitosan-based NP have been proposed as a possible delivery intervention, which not only protect these APIs from GI degradation but also improves bioavailability [112]. Curcumin (CUR) is a polyphenol that has been studied extensively. It is derived from the rhizomes of *Curcuma longa* and active against a range of cancers in *in vitro* setups [113, 114]. However, preclinical and clinical data indicate that oral administration of CUR results in poor systemic bioavailability and high susceptibility to metabolic degradation [115]. In a study by AlKhader et al., the pharmacokinetic and anti-colon cancer properties of curcumin-containing chitosan-pectinate NP (CUR-CS-PEC-NPs) were evaluated. The cellular uptake and subsequent anti-proliferative effects of the CUR-CS-PEC-NPs were boosted at low CUR concentration after 48 and 72 hours of treatment compared to free CUR at equivalent dose. Besides, the carrier provided protection to CUR from acidic degradation. After oral administration of CUR-CS-PEC-NPs and free CUR at

at the C-2 position within the glucosamine. Low molecular weight

in high molecular chitosan derived NP interact with the

*DOI: http://dx.doi.org/10.5772/intechopen.95363*

*4.4.2 Anti-bacterial agent delivery*

+

+

charged – NH3

Conversely, the NH3

#### *Gastrointestinal Delivery of APIs from Chitosan Nanoparticles DOI: http://dx.doi.org/10.5772/intechopen.95363*

Gemcitabine (Gem) is a widely prescribed anticancer agent used in pancreatic, lung and advanced colon cancer. Oral administration of Gem results in low oral bioavailability, high first-pass clearance gastrointestinal toxicity, such as nausea, vomiting and diarrhoea [107]. Hosseinzadeh et al. synthesised and characterised chitosan/Pluronic® F-127 (Gem-Chi/PF) NP in oral delivery of Gem for the treatment of colon cancer. *In vitro* studies showed that the NP presented enhanced cytotoxicity effects against HT-29 cell line and concluded that Gem-Chi/PF NP is a potential candidate for colon cancer treatment [108].
