Microparticles and nanoparticles-based approaches to improve oral treatment of Helicobacter pylori infection.

Helicobacter pylori is a gram-negative, spiral-shaped, flagellated bacterium that colonizes the stomach of half the world's population. Helicobacter pylori infection causes pathologies of varying severity. Standard oral therapy fails in 15-20% since the barriers of the oral route decrease the bioavailability of antibiotics and the intrinsic factors of bacteria increase the rates of resistance. Nanoparticles and microparticles are promising strategies for drug delivery into the gastric mucosa and targeting H. pylori. The variety of building blocks creates systems with distinct colloidal, surface, and biological properties. These features improve drug-pathogen interactions, eliminate drug depletion and overuse, and enable the association of multiple actives combating H. pylori on several fronts. Nanoparticles and microparticles are successfully used to overcome the barriers of the oral route, physicochemical inconveniences, and lack of selectivity of current therapy. They have proven efficient in employing promising anti-H. pylori compounds whose limitation is oral route instability, such as some antibiotics and natural products. However, the current challenge is the applicability of these strategies in clinical practice. For this reason, strategies employing a rational design are necessary, including in the development of nano- and microsystems for the oral route.

Effect of biotransformation by liver S9 enzymes on the mutagenicity and cytotoxicity of melanin extracted from Aspergillus nidulans.

CONTEXT: A mutant that exhibited increased melanin pigment production was isolated from Aspergillus nidulans fungus. This pigment has aroused biotechnological interest due to its photoprotector and antioxidant properties. In a recent study, we showed that melanin from A. nidulans also inhibits NO and TNF-α production. OBJECTIVE: The present study evaluates the mutagenicity and cytotoxicity of melanin extracted from A. nidulans after its exposure to liver S9 enzymes. MATERIALS AND METHODS: The cytotoxicity of multiple concentrations of melanin (31.2-500 µg/mL) against the McCoy cell line was evaluated using the Neutral Red assay, after incubation for 24 h. Mutagenicity was assessed using the Ames test with the Salmonella typhimurium strains TA98, TA97a, TA100, and TA102 at concentrations ranging from 125 µg/plate to 1 mg/plate after incubation for 48 h. RESULTS: The cytotoxicity of A. nidulans melanin after incubation with S9 enzymes was less than (CI50 value= 413.4 ± 3.1 µg/mL) that of other toxins, such as cyclophosphamide (CI50 value = 15 ± 1.2 µg/mL), suggesting that even the metabolised pigment does not cause significant damage to cellular components at concentrations up to 100 µg/mL. In addition, melanin did not exhibit mutagenic properties against the TA 97a, TA 98, TA 100, or TA 102 strains of S. typhimurium, as shown by a mutagenic index (MI)  <2 in all assays. DISCUSSION AND CONCLUSION: The significance of these results supports the use of melanin as a therapeutic reagent because it possesses low cytotoxicity and mutagenic potential, even when processed through an external metabolising system.