Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity

Lucarini, Simone; Fagioli, Laura; Campana, Raffaella; Cole, Hannah L.; Duranti, Andrea; Baffone, Wally; Vllasaliu, Driton; Casettari, Luca

doi:10.1016/j.ejpb.2016.06.022

Cited by 46 publications

(64 citation statements)

References 29 publications

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“…Lipozyme ® (0.078 g) was added to a solution of the fatty acid ( 1a – d ) (0.79 mmol) and 4- O -(3′,4′- O -isopropylidene-β-D-galactopyranosyl)-2,3:5,6-di- O -isopropylidene-1,1-di- O -methyl-D-glucopyranose (lactose tetra acetate, LTA) [ 26 ] ( 2 ) (0.402 g, 0.79 mmol) in water-saturated toluene at 25 °C [ 12 , 27 ]. The mixture was stirred at 75 °C for 12 h, cooled and diluted with acetone, then the enzyme was filtered, and the filtrate was concentrated.…”

Section: Methodsmentioning

confidence: 99%

“…Many studies have recently reported the synthesis and possible applications of selective 6- O -sugar fatty acid monoesters, generally referred as sugar monoesters [ 7 , 8 , 9 ]. Several physico-chemical and biological properties have been studied [ 10 , 11 ], to develop advanced drug delivery systems, including skin penetration enhancing effect or transmucosal permeability enhancement [ 12 , 13 , 14 , 15 ]. The use of amphiphilic compounds as permeability enhancers (PEs) for transmucosal drug delivery represents one of the most promising application of surfactants in biopharmaceutics, able to provide a valid alternative (e.g., oral or pulmonary administration) to the conventional (e.g., injection) route of administrations of many therapeutic peptides [ 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Structure–Activity Relationships and In Vitro Toxicity Profile of Lactose-Based Fatty Acid Monoesters as Possible Drug Permeability Enhancers

et al. 2018

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Permeability enhancers are receiving increased attention arising from their ability to increase transepithelial permeability and thus, bioavailability of orally or pulmonary administered biopharmaceutics. Here we present the synthesis and the in vitro assaying of a series of lactose-based non-ionic surfactants, highlighting the relationship between their structure and biological effect. Using tensiometric measurements the critical micelle concentrations (CMCs) of the surfactants were determined and demonstrate that increasing hydrophobic chain length reduces surfactant CMC. In vitro testing on Caco-2 intestinal and Calu-3 airway epithelia revealed that cytotoxicity, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays, is presented for most of the surfactants at concentrations greater than their CMCs. Further biological study demonstrates that application of cytotoxic concentrations of the surfactants is associated with depolarizing mitochondrial membrane potential, increasing nuclear membrane permeability and activation of effector caspases. It is, therefore, proposed that when applied at cytotoxic levels, the surfactants are inducing apoptosis in both cell lines tested. Importantly, through the culture of epithelial monolayers on Transwell® supports, the surfactants demonstrate the ability to reversibly modulate transepithelial electrical resistance (TEER), and thus open tight junctions, at non-toxic concentrations, emphasizing their potential application as safe permeability enhancers in vivo.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis, Structure–Activity Relationships and In Vitro Toxicity Profile of Lactose-Based Fatty Acid Monoesters as Possible Drug Permeability Enhancers

et al. 2018

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“…General Procedure for the Synthesis of Lactose Fatty Acid Ester Derivatives (3a-e) Lipozyme ® (0.078 g) was added to a solution of the opportune fatty acid (1a-e) (0.79 mmol) and 4-O-(3',4'-O-isopropylidene-α-d-galactopyranosyl)-2,3:5,6-di-O-isopropylidene-1,1-di-O-methyl-Dglucopyranose (lactose tetra acetal, LTA)[45] (2) (0.402 g, 0.79 mmol) in dry toluene (0.5 mL) at 30 • C[46,47]. The mixture was stirred at 75 • C for 12 h, cooled and diluted with acetone, then the enzyme was filtered and the filtrate was concentrated.…”

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confidence: 99%

Synthesis and Evaluation of Saccharide-Based Aliphatic and Aromatic Esters as Antimicrobial and Antibiofilm Agents

et al. 2019

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A small library of sugar-based (i.e., glucose, mannose and lactose) monoesters containing hydrophobic aliphatic or aromatic tails were synthesized and tested. The antimicrobial activity of the compounds against a target panel of Gram-positive, Gram-negative and fungi was assessed. Based on this preliminary screening, the antibiofilm activity of the most promising molecules was evaluated at different development times of selected food-borne pathogens (E. coli, L. monocytogenes, S. aureus, S. enteritidis). The antibiofilm activity during biofilm formation resulted in the following: mannose C10 > lactose biphenylacetate > glucose C10 > lactose C10. Among them, mannose C10 and lactose biphenylacetate showed an inhibition for E. coli 97% and 92%, respectively. At MICs values, no toxicity was observed on Caco-2 cell line for all the examined compounds. Overall, based on these results, all the sugar-based monoesters showed an interesting profile as safe antimicrobial agents. In particular, mannose C10 and lactose biphenylacetate are the most promising as possible biocompatible and safe preservatives for pharmaceutical and food applications.

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“…The initial microbial experiment showed that MIC (or Minimum bactericidal concentration-MBC) values of both unmodified and modified PHA monomers and their glucose esters are in most cases higher than 500 µg mL −1 , which is 50,000 fold higher than commonly used antibiotics (Ciplofloxan, Fluxonazole) [38,39]. Nevertheless, the literature reports and our results show that SFAEs in general have a bacteriostatic effect if present in higher concentrations, which can be used for other than therapeutic purposes (e.g., in the cosmetic or food industries, as surfactants/emulsifiers) [20,21,40,41]. Therefore, we increased the tested concentrations up to 5000 µg mL −1 (Table 3).…”

Section: Antimicrobial Testingmentioning

confidence: 53%

Influence of Chemical Modifications of Polyhydroxyalkanoate-Derived Fatty Acids on Their Antimicrobial Properties

et al. 2019

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Sugar esters are bioactive compounds derived from renewable resources. They consist of a sugar moiety with attached non-polar part – usually a fatty acid. These compounds find uses in cosmetic, food and pharmaceutical industries as surfactants due to their physicochemical and antimicrobial activities. In this study we have produced fatty acids for sugar ester synthesis from bacterially derived polyesters, namely polyhydroxyalkanoates (PHAs). We have developed methodology to decorate PHA monomers with a fluorinated moiety. With aid of biocatalysis a series of glucose esters was created with unmodified and modified PHA monomers. All synthesised compounds showed moderate antimicrobial activity.

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Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity

Abstract: 13Sugar based surfactants conjugated with fatty acid chains are an emerging broad

Cited by 46 publications

References 29 publications

Synthesis, Structure–Activity Relationships and In Vitro Toxicity Profile of Lactose-Based Fatty Acid Monoesters as Possible Drug Permeability Enhancers

Synthesis, Structure–Activity Relationships and In Vitro Toxicity Profile of Lactose-Based Fatty Acid Monoesters as Possible Drug Permeability Enhancers

Synthesis and Evaluation of Saccharide-Based Aliphatic and Aromatic Esters as Antimicrobial and Antibiofilm Agents

Influence of Chemical Modifications of Polyhydroxyalkanoate-Derived Fatty Acids on Their Antimicrobial Properties

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