Engineering resveratrol-loaded chitosan nanoparticles for potential use against Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is a microorganism directly linked to severe clinical conditions affecting the stomach. The virulence factors and its ability to form biofilms increase resistance to conventional antibiotics, growing the need for new substances and strategies for the treatment of H. pylori infection. The trans-resveratrol (RESV), a bioactive polyphenol from natural sources, has a potential activity against this gastric pathogen. Here, Chitosan nanoparticles (NP) containing RESV (RESV-NP) were developed for H. pylori management. The RESV-NP were prepared using the ionic gelation method and characterized by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and, Cryogenic Transmission Electron Microscopy (Cryo - TEM). The encapsulation efficiency (EE) and in vitro release rate of RESV were quantified using high-performance liquid chromatography (HPLC). RESV-NP performance against H. pylori was evaluated by the quantification of the minimum inhibitory/bactericidal concentrations (MIC/MBC), time to kill, alterations in H. pylori morphology in its planktonic form, effects against H. pylori biofilm and in an in vitro infection model. RESV-NP cytotoxicity was evaluated against AGS and MKN-74 cell lines and by hemolysis assay. Acute toxicity was tested using Galleria mellonella model assays. RESV-NP showed a spherical shape, size of 145.3 ± 24.7 nm, polydispersity index (PDI) of 0.28 ± 0.008, and zeta potential (ZP) of + 16.9 ± 1.81 mV in DLS, while particle concentration was 3.12 x 1011 NP/mL (NTA). RESV-NP EE was 72 %, with full release within the first 5 min. In microbiological assays, RESV-NP presented a MIC/MBC of 3.9 µg/mL, a time to kill of 24 h for complete eradication of H. pylori. At a concentration of 2xMIC (7.8 µg/mL), RESV-NP completely eradicated the H. pylori biofilm, and in an in vitro infection model, RESV-NP (4xMIC - 15.6 µg/mL) showed a significant decrease in bacterial load (1 Log10CFU/mL) when compared to the H. pylori J99 control. In addition, they did not demonstrate a toxic character at MIC concentration for both cell lines. The use of the RESV-NP with mucoadhesion profile is an interesting strategy for oral administration of substances targeting gastric disorders, linked to H. pylori infections.

Amyloid-polysaccharide interfacial coacervates as therapeutic materials.

Coacervation via liquid-liquid phase separation provides an excellent opportunity to address the challenges of designing nanostructured biomaterials with multiple functionalities. Protein-polysaccharide coacervates, in particular, offer an appealing strategy to target biomaterial scaffolds, but these systems suffer from the low mechanical and chemical stabilities of protein-based condensates. Here we overcome these limitations by transforming native proteins into amyloid fibrils and demonstrate that the coacervation of cationic protein amyloids and anionic linear polysaccharides results in the interfacial self-assembly of biomaterials with precise control of their structure and properties. The coacervates present a highly ordered asymmetric architecture with amyloid fibrils on one side and the polysaccharide on the other. We demonstrate the excellent performance of these coacervates for gastric ulcer protection by validating via an in vivo assay their therapeutic effect as engineered microparticles. These results point at amyloid-polysaccharides coacervates as an original and effective biomaterial for multiple uses in internal medicine.

An overview of the use of central venous catheters impregnated with drugs or with inorganic nanoparticles as a strategy in preventing infections.

Central venous catheter (CVC) is a medical device widely used in therapeutics to avoid repetitive venipuncture. Although its use is advantageous, it is possible to highlight limitations, such as the risk of catheter-related bloodstream infections, caused by excessive manipulation and even the urgency at the time of insertion. These factors lead to an expensive treatment, often hampered by resistance to antimicrobial agents, exposing the patient the risk and even leading to death. The use of CVC impregnated with free drugs or incorporated with nanoparticles is a promising strategy for preventing the adherence of microorganisms in these devices and consequently in the prevention of the infections. Although most of the nanoparticles registered by the FDA for medical use are organic, several studies have reported the potential of inorganic nanoparticles for this purpose. Therefore, the present review seeks to highlight the current scenario of hospital infections related to the use of CVC and the importance of CVCs impregnated with drugs or incorporated with inorganic nanoparticles as an interesting strategy in combating infections assigned to the use of this medical device.

Nanotechnology-based lipid systems applied to resistant bacterial control: A review of their use in the past two decades.

The rate of infections caused by resistant bacteria to the antimicrobials available for human use grows exponentially every year, which generates major impacts on human health and the world economy. In the last two decades, human beings can witness the expressive increase in the Science and Technology worldwide, and areas such as Health Sciences have benefited from these advances in favor of human health, such as the advent of Pharmaceutical Nanotechnology as an important approach applied for bacterial infections treatment with resistance profile to available antibiotics. This review of the scientific literature brings the applicability of nanotechnology-based lipid systems as an innovative tool in the improvement of bacterial infections treatment. Important studies involving the use of liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, microemulsions and lipid nanocapsules were verified in the period from 2000 to 2020, where important scientific results were found and will serve as a basis for the use of these systems to remain in constant updating. This manuscript shows the use of these drug delivery systems as potential vehicles for antibacterial compounds, which opens a new hope in the complement of the antibacterial therapeutic arsenal. Important studies developed in the last 20 years are present in this review, and thus guarantees an update on the use of these drug delivery systems for researchers from different areas of Health Sciences.

Highlighting the use of micro and nanoparticles based-drug delivery systems for the treatment of Helicobacter pylori infections.

Due to the high adaptability of Helicobacter pylori and the low targeting specificity of the drugs normally used in pharmacological therapy, the strains are becoming increasingly resistant to these drugs, making it difficult to eradicate the infection. Thus, the search for new therapeutic approaches has been considered urgent. The incorporation of drugs in advanced drug delivery systems, such as nano and microparticles, would allow the improvement of the retention time in the stomach and the prolongation of drug release rates at the target site. Because of this, the present review article aims to highlight the use of micro and nanoparticles as important technological tools for the treatment of H. pylori infections, focussing on the main nanotechnological systems, including nanostructured lipid carriers, liposomes, nanoemulsion, metallic nanoparticles, and polymeric nanoparticles, as well as microtechnological systems such as gastroretentive dosage forms, among them mucoadhesive, magnetic and floating systems were highlighted.

Exploiting drug delivery systems for oral route in the peptic ulcer disease treatment.

Peptic ulcer disease (PUD) is a common condition that is induced by acid and pepsin causing lesions in the mucosa of the duodenum and stomach. The pathogenesis of PUD is a many-sided scenario, which involves an imbalance between protective factors, such as prostaglandins, blood flow, and cell renewal, and aggressive ones, like alcohol abuse, smoking, Helicobacter pylori colonisation, and the use of non-steroidal anti-inflammatory drugs. The standard oral treatment is well established; however, several problems can decrease the success of this therapy, such as drug degradation in the gastric environment, low oral bioavailability, and lack of vectorisation to the target site. In this way, the use of strategies to improve the effectiveness of these conventional drugs becomes interesting. Currently, the use of drug delivery systems is being explored as an option to improve the drug therapy limitations, such as antimicrobial resistance, low bioavailability, molecule degradation in an acid environment, and low concentration of the drug at the site of action. This article provides a review of oral drug delivery systems looking for improving the treatment of PUD.

The role of polysaccharides from natural resources to design oral insulin micro- and nanoparticles intended for the treatment of Diabetes mellitus: A review.

Oral administration of insulin (INS) would represent a revolution in the treatment of diabetes, considering that this route mimics the physiological dynamics of endogenous INS. Nano- and microencapsulation exploiting the advantageous polysaccharides properties has been considered an important technological strategy to protect INS against harsh conditions of gastrointestinal tract, in the same time that improve the permeability via transcellular and/or paracellular pathways, safety and in some cases even selectivity for targeting delivery of INS. In fact, some polysaccharides also give to the systems functional properties such as pH-responsiveness, mucoadhesiveness under specific physiological conditions and increased intestinal permeability. In general, all polysaccharides can be functionalized with specific molecules becoming more selective to the cells to which INS is delivered. The present review highlights the advances in the past 10 years on micro- and nanoencapsulation of INS exploiting the unique natural properties of polysaccharides, including chitosan, starch, alginate, pectin, and dextran, among others.

Exploiting solid lipid nanoparticles and nanostructured lipid carriers for drug delivery against cutaneous fungal infections.

Several types of cutaneous fungal infections can affect the population worldwide, such as dermatophytosis, cutaneous candidiasis, onychomycosis, and sporotrichosis. However, oral treatments have pronounced adverse effects, making the topical route an alternative to avoid this disadvantage. On the other hand, currently available pharmaceutical forms designed for topical application, such as gels and creams, do not demonstrate effective retention of biomolecules in the upper layers of the skin. An interesting approach to optimise biomolecules' activity in the skin is the use of nanosystems for drug delivery, especially solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which in the past decade has shown advantages like increased adhesiveness, great occlusive properties and higher biomolecule deposition in stratum corneum when designed for topical application. Considering the demand for more effective therapeutic alternatives and the promising characteristics of SLN and NLC for topical application, the present study sought to gather studies that investigated the potential of using SLN and NLC for the treatment of cutaneous fungal infections. Studies demonstrated that these nanosystems showed optimisation, mostly, of the effectiveness of biomolecules besides other biopharmaceutical properties, in addition to offering potential occlusion and hydration of the applied region.

Resveratrol isoforms and conjugates: A review from biosynthesis in plants to elimination from the human body.

The natural isomers of resveratrol, cis- and trans-resveratrol, are natural phenolic substances synthetized via the shikimate pathway and found in many sources, including grapes, peanuts, blackberries, pistachios, cacao, cranberries, and jackfruits. They have functional and pharmacological properties such as anticarcinogenic, antidiabetic, anti-inflammatory, and cardioprotective activities. The aim of this article is to review the data published on resveratrol and its isomers, and their biosynthesis in plants, food sources, health and toxic effects, and the excretion of their metabolites. Due to its contribution to the promotion of human health, it is convenient to gather more knowledge about its functional properties, food sources, and the interactions with the human body during the processes of eating, digestion, absorption, biotransformation, and excretion, to combine this information to improve the understanding of these substances.

In vitro and in vivo anti-Helicobacter pylori activity of Casearia sylvestris leaf derivatives.

ETHNOPHARMACOLOGICAL RELEVANCE: The number of bacterial strains that are resistant to multiple conventional antimicrobial agents is increasing. In this context, natural products have been widely used as a strategy to treat diseases caused by bacteria. Infections by Helicobacter pylori have attracted attention because they are directly related to severe gastric medical conditions. Casearia sylvestris Swartz, popularly known as guaçatonga, is largely employed to treat gastric disorders in Brazilian folk medicine. This plant species has aroused much interest mainly because it displays anti-inflammatory activity and can act as an antiulcer agent. AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-H. pylori action of C. sylvestris leaf derivatives incorporated or not in a nanostructured drug delivery system. MATERIALS AND METHODS: The essential oil (obtained by hydrodistillation) and ethanolic extract (obtained by maceration) were obtained from C. sylvestris leaves. The ethanolic extract was submitted to fractionation through solid phase extraction and column chromatography, to yield the ethanolic fractions. Hydrolyzed casearin J was achieved by submitting isolated casearin J to acid hydrolysis. The derivatives were chemically characterized by nuclear magnetic resonance (NMR), gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS) analyses. A nanostructured lipid system was used as drug delivery system. To assess the in vitro antibacterial activity of C. sylvestris leaf essential oil, ethanolic extract, and derivatives, microdilution, biofilm, and time-kill assays were performed against H. pylori ATCC 43504. Finally, the in vivo action was investigated by employing male Wistar rats experimentally infected with H. pylori. RESULTS: Many C. sylvestris leaf derivatives presented significant in vitro activity against H. pylori. Among the derivatives, fraction 2 (F2) was the most effective. In vivo tests showed that both the ethanolic extract and F2 decreased the ulcerative lesion size, but only the ethanolic extract eradicated H. pylori from the gastric lesions. Incorporation of plant derivatives in nanostructured lipid system blunted the in vitro action, as demonstrated by the microdilution assay. However, this incorporation improved the ethanolic extract activity against biofilms. CONCLUSION: C. sylvestris leaf derivatives are effective against H. pylori both in vitro and in vivo. According to phytochemical analyses, these derivatives are rich in terpenoids, which could be related to the anti-H. pylori action. Synergism could also underlie C. sylvestris efficacy judging from the fact that the sub-fractions and isolated compounds had lower activity than the extract. Incorporation in a nanostructured lipid system did not improve the activity of the compounds in our in vivo protocol.

Nanotechnology-based drug delivery systems for control of microbial biofilms: a review.

Since the dawn of civilization, it has been understood that pathogenic microorganisms cause infectious conditions in humans, which at times, may prove fatal. Among the different virulent properties of microorganisms is their ability to form biofilms, which has been directly related to the development of chronic infections with increased disease severity. A problem in the elimination of such complex structures (biofilms) is resistance to the drugs that are currently used in clinical practice, and therefore, it becomes imperative to search for new compounds that have anti-biofilm activity. In this context, nanotechnology provides secure platforms for targeted delivery of drugs to treat numerous microbial infections that are caused by biofilms. Among the many applications of such nanotechnology-based drug delivery systems is their ability to enhance the bioactive potential of therapeutic agents. The present study reports the use of important nanoparticles, such as liposomes, microemulsions, cyclodextrins, solid lipid nanoparticles, polymeric nanoparticles, and metallic nanoparticles, in controlling microbial biofilms by targeted drug delivery. Such utilization of these nanosystems has led to a better understanding of their applications and their role in combating biofilms.

Essential Oil of Cymbopogon nardus (L.) Rendle: A Strategy to Combat Fungal Infections Caused by Candida Species.

BACKGROUND: The incidence of fungal infections, especially those caused by Candida yeasts, has increased over the last two decades. However, the indicated therapy for fungal control has limitations. Hence, medicinal plants have emerged as an alternative in the search for new antifungal agents as they present compounds, such as essential oils, with important biological effects. Published data demonstrate important pharmacological properties of the essential oil of Cymbopogon nardus (L.) Rendle; these include anti-tumor, anti-nociceptive, and antibacterial activities, and so an investigation of this compound against pathogenic fungi is interesting. OBJECTIVE: The aim of this study was to evaluate the chemical composition and biological potential of essential oil (EO) obtained from the leaves of C. nardus focusing on its antifungal profile against Candida species. METHODS: The EO was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Testing of the antifungal potential against standard and clinical strains was performed by determining the minimal inhibitory concentration (MIC), time-kill, inhibition of Candida albicans hyphae growth, and inhibition of mature biofilms. Additionally, the cytotoxicity was investigated by the IC50 against HepG-2 (hepatic) and MRC-5 (fibroblast) cell lines. RESULTS: According to the chemical analysis, the main compounds of the EO were the oxygen-containing monoterpenes: citronellal, geranial, geraniol, citronellol, and neral. The results showed important antifungal potential for all strains tested with MIC values ranging from 250 to 1000 µg/mL, except for two clinical isolates of C. tropicalis (MIC > 1000 µg/mL). The time-kill assay showed that the EO inhibited the growth of the yeast and inhibited hyphal formation of C. albicans strains at concentrations ranging from 15.8 to 1000 µg/mL. Inhibition of mature biofilms of strains of C. albicans, C. krusei and C. parapsilosis occurred at a concentration of 10× MIC. The values of the IC50 for the EO were 96.6 µg/mL (HepG-2) and 33.1 µg/mL (MRC-5). CONCLUSION: As a major virulence mechanism is attributed to these types of infections, the EO is a promising compound to inhibit Candida species, especially considering its action against biofilm.