Biosurfactants: properties and applications in drug delivery, biotechnology and ecotoxicology

Surfactants are amphiphilic compounds having hydrophilic and hydrophobic moieties in their structure. They can be of synthetic or of microbial origin, obtained respectively from chemical synthesis or from microorganisms activity. A new generation of ecofriendly surfactant molecules or biobased surfactants is increasingly growing, attributed to their versatility of applications. Surfactants can be used as drug delivery systems for a range of molecules given their capacity to create micelles which can promote the encapsulation of bioactives of pharmaceutical interest; besides, these assemblies can also show antimicrobial properties. The advantages of biosurfactants include their high biodegradability profile, low risk of toxicity, production from renewable sources, functionality under extreme pH and temperature conditions, and long-term physicochemical stability. The application potential of these types of polymers is related to their properties enabling them to be processed by emulsification, separation, solubilization, surface (interfacial) tension, and adsorption for the production of a range of drug delivery systems. Biosurfactants have been employed as a drug delivery system to improve the bioavailability of a good number of drugs that exhibit low aqueous solubility. The great potential of these molecules is related to their auto assembly and emulsification capacity. Biosurfactants produced from bacteria are of particular interest due to their antibacterial, antifungal, and antiviral properties with therapeutic and biomedical potential. In this review, we discuss recent advances and perspectives of biosurfactants with antimicrobial properties and how they can be used as structures to develop semisolid hydrogels for drug delivery, in environmental bioremediation, in biotechnology for the reduction of production costs and also their ecotoxicological impact as pesticide alternative.This work was supported by the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) through the grants M-ERA-NET/0004/2015 (PAIRED), UIDB/04469/2020 (strategic fund), and UIDB/04033/2020 (CITAB), cofinanced by FEDER, under the Partnership Agreement PT2020. T. Pashirova acknowledges the financial support received from the government assignment for FRC Kazan Scientific Center of Russian Academy of Sciences.info:eu-repo/semantics/publishedVersio

Soft cationic nanoparticles for drug delivery: production and cytotoxicity of solid lipid nanoparticles (SLNs)

The surface properties of nanoparticles have decisive influence on their interaction with biological barriers (i.e., living cells), being the concentration and type of surfactant factors to have into account. As a result of different molecular structure, charge, and degree of lipophilicity, different surfactants may interact differently with the cell membrane exhibiting different degrees of cytotoxicity. In this work, the cytotoxicity of two cationic solid lipid nanoparticles (SLNs), differing in the cationic lipids used as surfactants CTAB (cetyltrimethylammonium bromide) or DDAB (dimethyldioctadecylammonium bromide), referred as CTAB-SLNs and DDAB-SLNs, respectively, was assessed against five different human cell lines (Caco-2, HepG2, MCF-7, SV-80, and Y-79). Results showed that the cationic lipids used in SLN production highly influenced the cytotoxic profile of the particles, with CTAB-SLNs being highly cytotoxic even at low concentrations (IC50 < 10 µg/mL, expressed as CTAB amount). DDAB-SLNs produced much lower cytotoxicity, even at longer exposure time (IC50 from 284.06 ± 17.01 µg/mL (SV-80) to 869.88 ± 62.45 µg/mL (MCF-7), at 48 h). To the best of our knowledge, this is the first report that compares the cytotoxic profile of CTAB-SLNs and DDAB-SLNs based on the concentration and time of exposure, using different cell lines. In conclusion, the choice of the right surfactant for biological applications influences the biocompatibility of the nanoparticles. Regardless the type of drug delivery system, not only the cytotoxicity of the drug-loaded nanoparticles should be assessed, but also the blank (non-loaded) nanoparticles as their surface properties play a decisive role both in vitro and in vivo.This research was funded by the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the project references M-ERA-NET/0004/2015 (PAIRED) and UID/AGR/04033/2019 (CITAB), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Calix[4]resorcinolarenes with alkylphosphonic fragments: Protolytic properties and interaction with lanthanum(III)

The protolytic and complexing properties of phosphorylated derivatives of calix[4]resorcinolarenes were studied by pH-metric titration at 298 K in water-2-propanol (80 vol % 2-propanol). It was shown that calix[4] resorcinolarene containing the propylphosphonic acid fragment at the C atom linking the aryl groups exists in solution mainly as tetramer. At pH > 4, the anions of tetrameric, dimeric, and monomeric forms of this compound are formed. The neutral form of aminomethylated calix[4]resorcinolarene contaning, along with the propylphosphonic acid fragment, the CH2NEt2 group on the opposite side of the molecule is monomeric. It exists as a zwitterion and contains four betaine protons. Three dimeric species of this compound, one protonated and two deprotonated, were revealed. The dissociation constants of the phosphonate groups and two betaine protons were evaluated. The other two betaine protons and the protons of hydroxy groups do not dissociate. The equilibrium constants of the complex formation with lanthanum(III) and in some cases the stability constants of the complexes were calculated. Probable modes of coordination of calix[4]resorcinolarenes are discussed. Depending on the acidity of the medium, the competition between the phosphonic group and the phenolate ions takes place, and complexes with the coordination via phosphonic groups can rearrange into complexes with the coordination via phenolate groups. © Pleiades Publishing, Inc., 2006

Development and characterization of biointeractive gelatin wound dressing based on extract of Punica granatum Linn

Punica granatum Linn (pomegranate) extracts have been proposed for wound healing due to their antimicrobial, antioxidant, and anti-inflammatory properties. In this work, we designed biointeractive membranes that contain standard extracts of P. granatum for the purpose of wound healing. The used standard extract contained 32.24 mg/g of gallic acid and 41.67 mg/g of ellagic acid, and it showed high antioxidant activity (the concentration of the extract that produces 50% scavenging (IC50) 1.715 µg/mL). Compared to the gelatin-based membranes (GEL), membranes containing P. granatum extracts (GELPG) presented a higher maximal tension (p=0.021) and swelling index (p=0.033) and lower water vapor permeability (p=0.003). However, no difference was observed in the elongation and elastic modulus of the two types of membranes (p > 0.05). Our wound-healing assay showed that a GELPG-treated group experienced a significant increase compared to that of the control group in their wound contraction rates on days 3 (p < 0.01), 7 (p < 0.001), and on day 14 (p < 0.001). The GELPG membranes promoted major histological changes in the dynamics of wound healing, such as improvements in the formation of granular tissue, better collagen deposition and arrangement, and earlier development of cutaneous appendages. Our results suggest that a biointeractive gelatin-based membrane containing P. granatum extracts has a promising potential application for dressings that are used to treat wounds.The research was funded by FAPITEC/SE (Fundação de Apoio à Pesquisa e Inovação Tecnológica do Estado de Sergipe) and by the Brazilian Bureau of Research. T. Pashirova received the financial support from the government assignment for the FRC Kazan Scientific Center of Russian Academy of Sciences. E.B. Souto received the support from the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020, granted by the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds and co-financed by FEDER under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Micellization of alkylated 1.4-diazabicyclo[2.2.2]octane by nuclear magnetic resonance technique using pulsed gradient of static magnetic field

A phenomenon of micellization of 4-aza-1-tetradecyl-1-azoniabicyclo[2.2.2] octane bromide (AB-14) in aqueous solution has been studied by the methods of nuclear magnetic resonance using magnetic field pulse gradient and fluorimetry. The critical micelle concentration is determined; concentration dependences of percentage of free AB-14 molecules and those associated with micelles as well as radii of micelles and numbers of their aggregation are established. Effect of external and internal translational diffusion of molecules on lifetime of AB-14 molecules in micelles is investigated. © 2012 Elsevier B.V

Complexes of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide with transition metal nitrates. Micelle-forming, solubilizing, and adsorption properties

© 2017, Pleiades Publishing, Ltd. Amphiphilic complexes of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide (D-16) with nitrates of transition metals (La 3+ , Cu 2+ , Ni 2+ , and Co 2+ ) have been synthesized and characterized. Absorption spectrophotometry in the UV, visible, and IR regions, as well as 1 Н NMR spectroscopy, have been employed to study their spectral properties in water and organic media. Adsorption properties and micelleforming and solubilizing abilities of the amphiphilic complexes have been investigated in aqueous solutions by the methods of tensiometry and conductometry, as well as by solubilization of a water-insoluble dye (Orange OT). The values of the critical micelle concentration, adsorption parameters at a water/air interface, and solubilization capacity S of complex micelles have been determined. It has been shown that the most pronounced decrease in the critical micelle concentration (as large as two to three times) and differences in the adsorption characteristics and the S values as compared with those of ligand D-16 are observed for complexes of copper and lanthanum. The S values for these complexes are 1.3−2.5 and 3−6.5 times higher than those for D-16 and cetyltrimethylammonium bromide, respectively

Novel self-assembling system based on resorcinarene and cationic surfactant

Mixed association of calix[4]resorcinarene with ethyl sulfonate groups on the lower rim and dimethylaminomethyl groups on the upper rim (CR) and cationic surfactant 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide (DABCO-16) is studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy at fixed CR concentration and varied surfactant concentration. Beyond ca. 0.4 mM of DABCO-16, mixed aggregates enriched by CR are proved to be formed due to electrostatic forces, while beyond ca. 5 mM, aggregates enriched by surfactant occur due to the hydrophobic effect. Spectrophotometry monitoring of the solubilization of a hydrophobic dye, Orange OT, demonstrated that only the second type of mixed aggregate enriched by DABCO-16 is capable of binding the organic probe, while the mixed system where the surfactant is a minor component shows no binding capacity towards Orange OT. This finding can be used for the design of nanocontainers with controllable binding/release properties.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Nontoxic antimicrobial micellar systems based on mono- and di-cationic Dabco-surfactants and furazolidone: Structure-solubilization properties relationships

Supplementary data to this article can be found online at https://doi.org/10.1016/j.molliq.2019.112062.Self-assembly and solubilization properties of amphiphilic mono- and bisquaternized derivatives of 1,4-diazabicyclo[2.2.2]octane (mono-CS-n and di-CS-n, where CS cationic surfactant, n=12, 14, 16, 18) was investigated by nuclear magnetic resonance with magnetic field pulse gradient. The influence of Dabco-surfactant structure (head group and length of alkyl chains) on critical micelle concentration and aggregation number of micelles was studied. The CMC of mono-CS-n are lower than CMC of di-CS-n. The aggregation numbers of mono-CS-n micelles are higher than for di-CS-n micelles. The solubilization capacity of mono-CS-n is higher than di-CS-n. The solubilization capacity of mono-CS-16 is 2.5 times higher than CTAB in the case of Orange OT as a solute, and it is close to CTAB in the case of Sudan I. The solubility of a poorly water-soluble antibacterial drug furazolidone was improved by micellar solubilization based on mono- and di-Dabco-surfactants. Mono-CS-n is the best solubilizing agents toward furazolidone. The use of mixed composition mono-Dabco-16-furazolidone provides a significant increase in antimicrobial activity (2 times against bacteria and 8 times against fungi) and reduces 2 times the dose of each of the components in combination formulation and causes <2% haemolysis of human red blood cells at the active dose.The report study was funded by Russian Foundation for Basic Research according to the research project № 18-43-160015. The authors gratefully acknowledge the CSF-SAC FRC KSC RAS.info:eu-repo/semantics/publishedVersio

Synthesis, biological evaluation and structure-activity relationships of self-assembled and solubilization properties of amphiphilic quaternary ammonium derivatives of quinuclidine

© 2018 Elsevier B.V. This work deals with development of polyfunctional biocompatible cationic surfactant systems based on bioactive saturated bicyclic alkaloid quinuclidine. It is focused on the effect of the chemical structure of surfactants on their aggregation behavior, their physicochemical estimation of solubility of model water insoluble dye Orange OT and drugs, quercetin and rutin, microbiology and cytotoxicity. Quaternary ammonium derivatives of quinuclidine (Q-Nuc-n) with different hydrophobicity (R = CnH2n+1, where n = 14, 16, 18) were synthesized. Self-assembly of Q-Nuc-n was investigated by tensiometry, conductometry, spectrophotometry, fluorimetry and dynamic light scattering. The critical micelle concentration, thermodynamic and adsorption parameters at water-air interface, size and aggregation numbers of Q-Nuc-n micelles were determined. The looser packing of surfactant molecules in Q-Nuc-n micelles compared to its analogues, quaternized derivatives of 1,4‑diazabicyclo[2.2.2]octane (DABCO-n), was established. The hydrophobic dye Orange OT and drugs quercetin and rutin were solubilized in micellar Q-Nuc-n solutions better than in solutions of classical surfactant CTAB and its analogue DABCO-n. Solubilization capacity of Q-Nuc-18 is 5 times higher than that of classical surfactant CTAB. Q-Nuc-18 1.95 μg·mL−1 has also bactericidal and fungicidal activity 2 times (against S. aureus 209P) and 8 times (against B. cereus 8035) higher than antibiotics Norfloxacin and antifungal Ketoconazole. Q-Nuc-16 has the highest bactericidal activity. It is 6 times (against S. aureus 209P) and 15 times (against B. cereus 8035) higher than the bactericidal activity value of Norfloxacin. Synthesized cationic surfactants based on quinuclidine are new multifunctional biocompatible compounds with high potential in nanomedicine and biotechnology