Drug delivery in overcoming the blood-brain barrier: role of nasal mucosal grafting

The blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful

Neem oil nanoemulsions: characterisation and antioxidant activity

The aim of the present work is to develop nanoemulsions (NEs), nanosized emulsions, manufactured for improving the delivery of active pharmaceutical ingredients. In particular, nanoemulsions composed of Neem seed oil, contain rich bioactive components, and Tween 20 as nonionic surfactant were prepared. A mean droplet size ranging from 10 to 100nm was obtained by modulating the oil/surfactant ratio. Physicochemical characterisation was carried out evaluating size, f-potential, microviscosity, polarity and turbidity of the external shell and morphology, along with stability in simulated cerebrospinal fluid (CSF), activity of Neem oil alone and in NEs, HEp-2 cell interaction and cytotoxicity studies. This study confirms the formation of NEs by Tween 20 and Neem oil at different weight ratios with small and homogenous dimensions. The antioxidant activity of Neem oil alone and in NEs was comparable, whereas its cytotoxicity was strongly reduced when loaded in NEs after interaction with HEp-2 cells

CARATTERIZZAZIONE ACUSTICA DI NANOBOLLE LIPIDICHE

Vengono riportate misure riguardo l’efficienza di scattering di nanobolle lipidiche con diametro medio di 200 nm contenenti tetradecafluoroesano; le misure, effettuate con la tecnica pulse-echo, rivelano un’attenuazione dipendente dalla concentrazione in soluzione delle nanobolle con valori che, per una concentrazione del 35% di nanobolle in hepes, raggiungono, a 14 MHz, il valore di circa 6 dB/cm. Tale valore è confrontabile con le attenuazioni prodotte da agenti di contrasto commercialmente disponibili come, ad esempio, il SonoVue®. È stata inoltre utilizzata una tecnica fotoacustica per la valutazione dell’efficacia di intrappolamento del gas all’interno delle nanobolle, riscontrando, anche in questo caso, valori simili a quelli misurati nel SonoVue®

Chitosan Glutamate-Coated Niosomes: a proposal for Nose-to-Brain delivery

The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM). Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration

Sustainable and Health-Protecting Food Ingredients from Bioprocessed Food by-Products and Wastes

Dietary inadequacy and nutrition-related non-communicable diseases (N-NCDs) represent two main issues for the whole society, urgently requesting solutions from researchers, policy-makers, and other stakeholders involved in the health and food system. Food by-products and wastes (FBPW) represent a global problem of increasing severity, widely recognized as an important unsustainability hotspot, with high socio-economic and environmental costs. Yet, recycling and up-cycling of FBPW to produce functional foods could represent a solution to dietary inadequacy and risk of N-NCDs onset. Bioprocessing of FBPW with selected microorganisms appears to be a relatively cheap strategy to yield molecules (or rather molecules mixtures) that may be used to fortify/enrich food, as well as to formulate dietary supplements. This review, conjugating human health and sustainability in relation to food, describes the state-of-the-art of the use of yeasts, molds, and lactic acid bacteria for producing value-added compounds from FBPW. Challenges related to FBPW bioprocessing prior to their use in food regard will be also discussed: (i) loss of product functionality upon scale-up of recovery process; (ii) finding logistic solutions to the intrinsic perishability of the majority of FBPW; (iii) inserting up-cycling of FBPW in an appropriate legislative framework; (iv) increasing consumer acceptability of food and dietary supplements derived from FBPWThis research was funded by the project SYSTEMIC “an integrated approach to the challenge of sustainable food systems: adaptive and mitigatory strategies to address climate change and malnutrition”, Knowledge hub on Nutrition and Food Security, that has received funding from national research funding parties in Belgium (FWO), France (INRA), Germany (BLE), Italy (MIPAAF), Latvia (IZM), Norway (RCN), Portugal (FCT), and Spain (AEI) in a joint action of JPI HDHL, JPI-OCEANS and FACCE-JPI launched in 2019 under the ERA-NET ERAHDHL (n° 696295). Francisca Rodrigues (CEECIND/01886/2020) is thankful for her contract financed by FCT/MCTES—CEEC Individual 2020 Program Contractinfo:eu-repo/semantics/publishedVersio

Massive survey on bacterial–bacteriophages biodiversity and quality of natural whey starter cultures in Trentingrana cheese production

9openInternationalItalian coauthor/editorThis study focused on the microbial and bacteriophages identification and characterization in cheese-production facilities that use natural whey starter (NWS) cultures for Trentingrana production. Bacterial and phage screening was carried out on cooked not acidified whey and NWS samples isolated from six dairy factories, for 4 consecutive days in four different months. By means of a combined approach, using plate counts, bacterial isolation, and metataxonomic analysis Lactobacillus helveticus was found occurring as the dominant species in NWS cultures and Levilactobacillus brevis as codominant in the cheese factories where the temperature of NWS production was mainly lower than 40°C, suggesting that the variability in the parameters of the NWS culture preparation could differently modulate the bacterial species in NWS cultures. Using turbidity test approach on 303 bacterial isolates from the NWS cultures, 120 distinct phages were identified. L. helveticus phage contamination of NWS cultures was revealed in most of the analyzed samples, but despite the great recovery of bacteriophage contamination cases, the microbial quality of NWS cultures was high. Our results support the presence of natural bacteriophage resistance mechanisms in L. helveticus. The use of NWS cultures probably creates an ideal environment for the proliferation of different L. helveticus strains balanced with their phages without a clear dominance. It is evident, from this study, that the presence of a high biodiversity of NWS bacterial strains is relevant to avoid phages dominance in NWS cultures and consequently to keep a good acidification ability.openMancini, A.; Cid Rodriguez, M.; Zago, M.; Cologna, M.; Goss, A.; Carafa, I.; Tuohy, K.; Merz, A.; Franciosi, E.Mancini, A.; Cid Rodriguez, M.; Zago, M.; Cologna, M.; Goss, A.; Carafa, I.; Tuohy, K.; Merz, A.; Franciosi, E

Influence of drug/lipid interaction on the entrapment efficiency of isoniazid in liposomes for antitubercular therapy: a multi-faced investigation

Hypothesis. Isoniazid is one of the primary drugs used in tuberculosis treatment. Isoniazid encapsulation in liposomal vesicles can improve drug therapeutic index and minimize toxic and side effects. In this work, we consider mixtures of hydrogenated soy phosphatidylcholine/phosphatidylglycerol (HSPC/DPPG) to get novel biocompatible liposomes for isoniazid pulmonary delivery. Our goal is to understand if the entrapped drug affects bilayer structure. Experiments. HSPC-DPPG unilamellar liposomes are prepared and characterized by dynamic light scattering, $\zeta$-potential, fluorescence anisotropy and Transmission Electron Microscopy. Isoniazid encapsulation is determined by UV and Laser Transmission Spectroscopy. Calorimetry, light scattering and Surface Pressure measurements are used to get insight on adsorption and thermodynamic properties of lipid bilayers in the presence of the drug. Findings. We find that INH-lipid interaction can increase the entrapment capability of the carrier due to isoniazid adsorption. The preferential INH-HSPC dipole-dipole interaction promotes modification of lipid packing and ordering and favors the condensation of a HSPC-richer phase in molar excess of DPPG. Our findings highlight the importance of fundamental investigations of drug-lipid interactions for the optimal design of liposomal nanocarriers.Comment: 28 pages (main manuscript + supplementary information

Effect of ciprofloxacin-loaded niosomes on escherichia coli and staphylococcus aureus biofilm formation

Infections caused by bacterial biofilms represent a global health problem, causing considerable patient morbidity and mortality in addition to an economic burden. Escherichia coli, Staphylococcus aureus, and other medically relevant bacterial strains colonize clinical surfaces and medical devices via biofilm in which bacterial cells are protected from the action of the immune system, disinfectants, and antibiotics. Several approaches have been investigated to inhibit and disperse bacterial biofilms, and the use of drug delivery could represent a fascinating strategy. Ciprofloxacin (CIP), which belongs to the class of fluoroquinolones, has been extensively used against various bacterial infections, and its loading in nanocarriers, such as niosomes, could support the CIP antibiofilm activity. Niosomes, composed of two surfactants (Tween 85 and Span 80) without the presence of cholesterol, are prepared and characterized considering the following features: hydrodynamic diameter, ζ-potential, morphology, vesicle bilayer characteristics, physical-chemical stability, and biological efficacy. The obtained results suggest that: (i) niosomes by surfactants in the absence of cholesterol are formed, can entrap CIP, and are stable over time and in artificial biological media; (ii) the CIP inclusion in nanocarriers increase its stability, with respect to free drug; (iii) niosomes preparations were able to induce a relevant inhibition of biofilm formation

Rifampicin-liposomes for mycobacterium abscessus infection treatment: intracellular uptake and antibacterial activity evaluation

: Treatment of pulmonary infections caused by Mycobacterium abscessus are extremely difficult to treat, as this species is naturally resistant to many common antibiotics. Liposomes are vesicular nanocarriers suitable for hydrophilic and lipophilic drug loading, able to deliver drugs to the target site, and successfully used in different pharmaceutical applications. Moreover, liposomes are biocompatible, biodegradable and nontoxic vesicles and nebulized liposomes are efficient in targeting antibacterial agents to macrophages. The present aim was to formulate rifampicin-loaded liposomes (RIF-Lipo) for lung delivery, in order to increase the local concentration of the antibiotic. Unilamellar liposomal vesicles composed of anionic DPPG mixed with HSPC for rifampicin delivery were designed, prepared, and characterized. Samples were prepared by using the thin-film hydration method. RIF-Lipo and unloaded liposomes were characterized in terms of size, ζ-potential, bilayer features, stability and in different biological media. Rifampicin's entrapment efficiency and release were also evaluated. Finally, biological activity of RIF-loaded liposomes in Mycobacterium abscessus-infected macrophages was investigated. The results show that RIF-lipo induce a significantly better reduction of intracellular Mycobacterium abscessus viability than the treatment with free drug. Liposome formulation of rifampicin may represent a valuable strategy to enhance the biological activity of the drug against intracellular mycobacteria