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Phytochemicals have been found to be promising alternatives to conventional antibiotic therapies for the control of bacterial infections, as they may entail less selective pressure and hence reduce the development of resistance. This study involved examining the inhibition of biofilm formation and of quorum sensing (QS), and the cytotoxicity on mammalian cells of two flavonoids, quercetin and baicalein, in free form and associated into chitosan-based nanocapsules. This was done by use of a transformed E. coli Top 10 biosensor strain, while the cytotoxicity was evaluated on MDCK-C7 cells. In free form, application both flavonoids exhibited slight inhibitory activity on the QS response and biofilm formation, a scenario that was improved positively upon encapsulation with chitosan (Mw ∼115,000 g/mol and DA ∼42%). The association efficiency of 99% (quercetin) and 87% (baicalein) was determined, and each formulation had an average diameter of 190 ± 4 and 187 ± 2 nm, and zeta (ζ) potential of +48.1 ± 2.03 and +48.4 ± 3.46 mV, respectively. Both types of systems were stable against aggregation in M9 and MEM media. The in vitro release kinetics data of both flavonoids seemed to be similar with only ∼20% released over the first 5 h, or ∼10% over the first 4 h, respectively, with subsequent sudden release increase up to ∼40% in both cases. The free phytochemicals seemed to be cytotoxic to MDCK-C7 cells at higher doses, however, upon nanoencapsulation, a cytoprotective effect was evidenced. We have gained proof-of-principle of the advantages of encapsulation of two bioactive flavonoids.

The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) stomach infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario, geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context, the exploration of the biological activity of plant-derived products or polysaccharides commonly present in foods is increasingly becoming more and more attractive. This review aims to present the current state-of-the-art on the antiadhesive capacity of different polysaccharide families, on polysaccharide-based nanosystems and the proof-of-concept evidence of their potential use as alternative medicines against H. pylori.

Polysaccharide and proteins are the major constituent building blocks of biological systems and often occur as highly organized macromolecular architectures (e.g. the capsid of viruses). Both can occur in the same or in different biological physiological environment interacting in specific or non-specific ways. When isolated and purified, these macromolecules can harness self-assembled (SA) soft nanomaterials by non-covalent electrostatic complexation. Although polysaccharide-protein electrostatic SA systems of this type have been studied for more than two decades, the possibility to design materials with enhanced biological function and improved technological advantages over those based on synthetic or inorganic components, has only started to be recognized and is yet to be fully realized. In this review we address two main type of SA polysaccharide-protein systems, namely, those based on chitosan-protein and those based on polyanionic polysaccharide (pectin, hyaluronic acid or alginate) - protein ones. The physical properties of chitosan- and polyanion-based SA nanocomplexes with oppositely charged proteins depend on the composition and conditions as reviewed here with reference to some specific systems.

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Nanoparticles are produced by means of polyelectrolyte complexation (PEC) of oppositely charged polycationic chitosan (CH) with polyanionic polysaccharide extracted from Sterculia striata exudates (rhamnogalacturonoglycan (RG)-type polysaccharide). The nanoparticles formed with low-molar-mass CH are larger than those formed with high-molar-mass CH. This behavior is in contrast with that previously observed for other systems and may be attributed to different mechanisms related to the association of CH with RG of higher persistence length chain than that of CH. Nanoparticles harnessed with a charge ratio (n(+)/n(-)) of <1 are smaller than particles with an excess of polycations. Particles with hydrodynamic sizes smaller than 100nm are achieved using a polyelectrolyte concentration of 10(-4)gmL(-1) and charge ratio (n(+)/n(-)) of <1. The CH/RG nanoparticles are associated with chloroquine (CQ) with an efficiency of 28% and release it for up to ∼60% within ∼10h, whereas in the latter, only ∼40% of the CQ was released after 24h. The main factor that influenced drug release rate is the nanoparticle charge ratio.

Recently, much attention has been given to pulmonary drug delivery by means of nanosized systems to treat both local and systemic diseases. Among the different materials used for the production of nanocarriers, chitosan enjoys high popularity due to its inherent characteristics such as biocompatibility, biodegradability, and mucoadhesion, among others. Through the modification of chitosan chemical structure, either by the addition of new chemical groups or by the functionalization with ligands, it is possible to obtain derivatives with advantageous and specific characteristics for pulmonary administration. In this paper, we discuss the advantages of using chitosan for nanotechnology-based pulmonary delivery of drugs and summarize the most recent and promising modifications performed to the chitosan molecule in order to improve its characteristics.

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