*5.1.2 Anticancer drugs*

Curcumin has been described, among many other applications, to possess anticancer properties against different tumor types, including colorectal cancer. Nevertheless, it presents an inconveniently low bioavailability and a short average life, as well as a limited absorption and quick metabolism. The use of non-toxic nanocapsules prepared from the biodegradable polymer polyallyhydrocarbon proved useful for drugs with low bioavailability, including curcumin. The efficacy of these systems was confirmed with the use of mice as models [61]. In the same way, curcumin was encapsulated in systems prepared from chitosan and carboxymethyl cellulose which presented good stability [62] In Ref. [63], nanocapsules with different polymeric coatings (P80, PEG, chitosan, and Eudragit®) were prepared and compared as curcumin carriers. They evaluated the release of the active, cytotoxicity, and in this case, antimalaria activity was tested instead of antitumoral potential. The highest activity observed was that of nanocapsules prepared from chitosan. On the other hand, a curcumin-loaded nanostructure of hybrid lipid capsules of three different sizes has been shown to present 2.5 times the anti-cancerous efficacy of free curcumin in breast cancer cells and breast cancer stem-like cells [63, 64]. Also, liquid lipid nanocapsules coated with human serum albumin to carry curcumin were proposed. To strengthen the protecting role of the protein layer, this was cross-linked [65]. Moreover, liquid lipid nanocapsules were obtained from olive oil emulsification, where nanocapsules were coated by a protective shell composed of bovine serum albumin and hyaluronic acid [66]. The so-called nanocurcumin was also formulated, consisting of the anticancerous compound incorporated into a polymeric nanoparticle, which enhances its solubility. Due precisely to its solubility, its gelifying capacity and its ability to form complexes, pectin has also been widely used for the preparation of diverse nanomaterials, including nanocapsules. It presents medical uses as a coagulant, anti-diarrheic, anti-ulcerous, and anti-cancerous for colon cancer [106].

The anticancer drug docetaxel has been carried in multiple types of nanocapsules. As a novelty, nanocapsules were prepared that consisted of a polymeric shell coating an oily core, targeted to Tn-expressing carcinomas. Chitosan was PEGylated and

modified with a monoclonal antibody that recognizes the antigen Tn, which is highly specific for carcinomas. Internalization of nanoparticles and reduction of cellular viability were proved. The release is pH-dependent, being faster in acid pH, which favors intracellular release [67]. Also for docetaxel delivery, nanocapsules were formulated from hyaluronic acid through self-emulsification in absence of organic solvents. They were studied *in vitro* with lung cancer cells and an effective release of the drug was observed [68]. In addition, the system composed of docetaxel and thymoquinone co-encapsulated in PEGylated lipid nanocapsules was explored. Cytotoxicity was improved and enhanced antitumor efficacy and apoptotic effects were observed. Reduced oxidative stress and toxicity to liver and kidney tissues occurred [69]. Chitosan-coated PLC nanocapsules resulted effective for the oral administration of perillyl alcohol, an essential oil with chemo-preventive activity for anticancer therapy. These nanocapsules present the mucoadhesive properties of the oil [70]. Chitosan and gellan gum were combined in the preparation of natural nanocapsules for tamoxifen delivery [71]. Tamoxifen delivery in biocompatible nanocapsules made from a PLA core and a 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyet hyleneglycol)-2000] shell was studied for breast cancer treatment. Cell proliferation results indicated cytotoxicity of nanocapsules in MCF-7 cells, as compared to free tamoxifen [72].

The drug aprepitant is a selective neurokinin 1 antagonist with low solubility in water, clinically used for the prevention of vomits and sickness provoked by chemotherapy. Chitosan-PEG-coated cyclodextrin nanoparticles and nanocapsules were designed and evaluated *in vitro* and *in vivo* [73]. New topic formulations of the antitumoral drug 5-fluorouracil were studied using sodium alginate and hyaluronic acid-containing AS1411 aptamer-functionalized polymeric nanocapsules. It was proved that nanoencapsulation improves drug permeability, and the nanoparticles prepared showed favorable biosafety and good antitumor effects for skin cancer treatment [74]. To improve the efficiency of the antitumoral treatment, hybrid nanocapsules obtained from the interfacial condensation between chitosan and poly(N-vinyl pyrrolidone-alt-itaconic anhydride), containing both magnetic nanoparticles and 5-fluorouracil, were developed. Their nanometric size and their spherical shape were confirmed by SEM [75].

Polysaccharide-based nanocapsules prepared from furcellaran and chitosan via LBL deposition using electrostatic interaction were studied. To achieve targeted delivery, the surface was modified with a peptide. Doxorubicin was encapsulated with excellent drug loading properties, and release and stability proved to be influenced by pH. This system showed compatibility with eukaryotic organisms and good anticancer effects [76]. Paclitaxel, like most anticancer drugs, is low water-soluble and presents high toxicity at therapeutic doses. Nanoencapsulation seems a good strategy to overcome these difficulties. In Ref. [77] three kinds of nanocapsules using derivates of PEG dimethacrylates as crosslinking agents were obtained. It was possible to prove that the nanocapsule system provides an effective and universal strategy for lung targeting, esterase triggering, and synergy therapy. In another study, paclitaxel was loaded onto chitosan-poly(isobutyl cyanoacrylate) core-shell nanocapsules designed for oral drug delivery. The nanocapsules thus prepared had low polydispersity, spherical shape, and good mucoadhesive properties [78]. Another strategy for the encapsulation of paclitaxel and the reduction of its toxicity is the preparation of lipid and biosurfactant-based core-shell-type nanocapsules. In one such study, Acconon® was the lipid, and stearic-acid-valine conjugate the biosurfactant [79].
