Célia Faustino

Gemini surfactant-protein interactions: effect of pH, temperature, and surfactant stereochemistry.

The interactions between bovine serum albumin (BSA) and gemini surfactants derived from cystine have been investigated and were compared with the conventional single-chain surfactant derived from cysteine. The influence of the stereochemistry of the gemini surfactant on its behavior toward BSA was also investigated, as well as the effects of pH and temperature. Electrical conductivity and surface tension measurements were used to obtain important system parameters such as critical aggregation concentration (cac), polymer saturation point (psp), degree of ionization (alpha), and the amount of surfactant binding to protein (M). Stereochemistry was found to influence the surface properties of the surfactants studied and their interaction with BSA but not their micellar properties in solution.

Dimeric and monomeric surfactants derived from sulfur-containing amino acids

Anionic urea-based dimeric (gemini) surfactants derived from the amino acids L-cystine, D-cystine and DL-cystine, as well as monomeric surfactants derived from L-cysteine, L-methionine and L-cysteic acid were synthesized and their solution properties characterized by electrical conductivity, equilibrium surface tension, and steady-state fluorescence spectroscopy techniques. The geminis studied showed the lowest critical micelle concentration (cmc) values, however the monomeric cysteine counterpart exhibited superior efficiency in lowering surface tension, an unusual finding that can be attributed to the free sulfhydryl group. Chirality seems to play a role in the surface active properties of the gemini surfactants, but not on micelle formation. All the surfactants studied showed a higher preference for adsorption at the air/water interface rather than to form micelles, a fact that may be related to the urea moiety. The polarity of the interfacial region, measured with the solvatochromic probe E(T)(30) (Reichardts betaine dye), was similar to sodium dodecyl sulphate (SDS) micelles.

Mixed micelle formation between amino acid-based surfactants and phospholipids

The mixed micelle formation in aqueous solutions between an anionic gemini surfactant derived from the amino acid cystine (C(8)Cys)(2), and the phospholipids 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC, a micelle-forming phospholipid) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC, a vesicle-forming phospholipid) has been studied by conductivity and the results compared with the ones obtained for the mixed systems with the single-chain surfactant derived from cysteine, C(8)Cys. Phospholipid-surfactant interactions were found to be synergistic in nature and dependent on the type of phospholipid and on surfactant hydrophobicity. Regular solution theory was used to analyse the gemini surfactant-DHPC binary mixtures and the interaction parameter, β(12), has been evaluated, as well as mixed micelle composition. The results have been interpreted in terms of the interplay between reduction of the electrostatic repulsions among the ionic head groups of the surfactants and steric hindrances arising from incorporation of the zwitterionic phospholipids in the mixed micelles.

New urea-based surfactants derived from alpha,omega-amino acids.

New anionic urea-based surfactants derived from alpha,omega-amino acids and in particular from beta-alanine were synthesized and their solution properties characterized by electrical conductivity, equilibrium surface tension, and steady-state fluorescence spectroscopy techniques. Double-chain surfactants and the single-chain surfactant containing a sulfate head group exhibited the lowest critical micelle concentration (cmc) values and superior efficiency in lowering surface tension. All surfactants promoted adsorption relative to micellization, and micellar parameters were sensitive to the hydrophobicity of the amino acid residue. The polarity of the interfacial region, measured with the solvatochromic probe E(T)(30) (Reichardts betaine dye), was similar to sodium dodecyl sulfate (SDS) micelles.

Interactions between β-cyclodextrin and an amino acid-based anionic gemini surfactant derived from cysteine.

The interaction between β-cyclodextrin (β-CD) and an amino acid-based anionic gemini surfactant derived from cysteine (C(8)Cys)(2) was studied by three independent techniques: electrical conductivity, UV-Vis spectral displacement technique using phenolphthalein as probe, and (1)H NMR spectroscopy. The data obtained indicated the formation of a 1:1 inclusion complex between β-CD and the gemini surfactant studied and allowed for the determination of the binding constant, K(1), by considering this stoichiometry. Electrical conductivity, spectral displacement technique, and NMR chemical shift measurements, obtained for aqueous β-CD-surfactant systems, yielded consistent K(1) values in the order of 10(2) dm(3) mol(-1), typical of a weakly bound β-CD-surfactant complex. The influence of the presence of the inclusion complex on the micellization process of the gemini surfactant has also been studied and the apparent critical micelle concentration (cmc(∗)) has been obtained. Increasing β-CD concentration was found to shift the cmc(∗) to higher values, as complexed surfactant monomers are not available to form micelles and aggregation takes place only when all β-CD cavities are occupied.

Bile acids and bile acid derivatives: use in drug delivery systems and as therapeutic agents

ABSTRACT Introduction: Bile acids are biological surfactants and signaling molecules with important paracrine and endocrine functions. The enterohepatic organotropism of bile acids turns these facial amphiphiles into attractive drug delivery systems for selective drug targeting to the liver or to enhance drug bioavailability by improving intestinal absorption and metabolic stability. Areas covered: Bile acid-based amphiphiles, in the form of mixed micelles, bilosomes, drug conjugates and hybrid lipid-polymer nanoparticles are critically discussed as delivery systems for anticancer drugs, antimicrobial agents and therapeutic peptides/proteins, including vaccines. Therapeutic applications of bile acid derivatives as cytotoxic and neuroprotective agents are also addressed. Expert opinion: Bile acids play an important role in modulating cancer therapy and novel derivatives with cytotoxic activity not restricted to the gastrointestinal tract can be expected. Selective toxicity targeting the bacterial membrane remains an attractive area of research for further development of bile acid-based bactericidal agents. On the other hand, the neuroprotective properties of some bile acids offer therapeutic potential in neurodegenerative disorders. Bile acid-based nanoparticles are also a growing research area due to the unique characteristics and tunable properties of these nanosystems. Therefore, multifaceted pharmaceutical and biomedical applications of bile salts are to be expected in the near future.

Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer’s disease

&NA; Alzheimers disease (AD) is a progressive neurodegenerative disorder associated with amyloid‐&bgr; peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood‐brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell‐based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease‐modifying approach toward AD. Lipid‐ and polymer‐based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF‐based therapies. Graphical abstract Figure. No caption available.

Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B

Lipoamino acid-based micelles have been developed as delivery vehicles for the hydrophobic drug amphotericin B (AmB). The micellar solubilisation of AmB by a gemini lipoamino acid (LAA) derived from cysteine and its equimolar mixtures with the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC), as well as the aggregation sate of the drug in the micellar systems, was studied under biomimetic conditions (phosphate buffered-saline, pH 7.4) using UV-vis spectroscopy. Pure surfactant systems and equimolar mixtures were characterized by tensiometry and important parameters were determined, such as critical micelle concentration (CMC), surface tension at the CMC (γCMC), maximum surface excess concentration (Γmax), and minimum area occupied per molecule at the water/air interface (Amin). Rheological behaviour from viscosity measurements at different shear rates was also addressed. Solubilisation capacity was quantified in terms of molar solubilisation ratio (χ), micelle-water partition coefficient (KM) and Gibbs energy of solubilisation (ΔGs°). Formulations of AmB in micellar media were compared in terms of drug loading, encapsulation efficiency, aggregation state of AmB and in vitro antifungal activity against Candida albicans. The LAA-containing micellar systems solubilise AmB in its monomeric and less toxic form and exhibit in vitro antifungal activity comparable to that of the commercial formulation Fungizone.

Rosmarinus officinalis L.: an update review of its phytochemistry and biological activity

The worldwide interest in the use of medicinal plants has been growing, and its beneficial effects being rediscovered for the development of new drugs. Based on their vast ethnopharmacological applications, which inspired current research in drug discovery, natural products can provide new and important leads against various pharmacological targets. This work pioneers an extensive and an updated literature review on the current state of research on Rosmarinus officinalis L., elucidating which compounds and biological activities are the most relevant. Therefore, a search was made in the databases PubMed, ScienceDirect and Web of Science with the terms ‘rosemary’, ‘Rosmarinus officinalis’, ‘rosmarinic acid’ ‘carnosol’ and ‘carnosic acid’, which included 286 articles published since 1990 about rosemarys pharmacological activities and their isolated compounds. According to these references, there has been an increasing interest in the therapeutic properties of this plant, regarding carnosic acid, carnosol, rosmarinic acid and the essential oil. The present manuscript provides an updated review upon the most reported activities on R. officinalis and its active constituents.

Amino Acid-Based Surfactants for Biomedical Applications

The growing demand for surfactants worldwide has a profound impact on the environment and public health. The quest for environmentally friendly “green” surfactants has driven research toward bio-based surfactants from renewable sources with improved performances and low toxicity. Amino acid-based surfactants (AAS) are a promising class of biocompatible and biodegradable surfactants for biomedical applications due to their improved safety profiles that meet the requirements of both physiological and ecological compatibility. Natural amino acids are chiral compounds and important raw materials for production of AAS. The amino acid pool allows the synthesis of multifunctional surfactants with chiral properties that can be tailored for specific technological and/or biomedical applications. The nature of the amino acid residue, the chirality, and the ability for hydrogen bond formation strongly influences the surface active properties and self-assembly behavior of AAS. This review summarizes recent developments in AAS structure-property relationships providing valuable information for modulation of the surface active and biological properties of AAS to meet specific biomedical applications. The interaction of AAS with biointerfaces and biological molecules is also addressed concerning cellular toxicity and potential therapeutic applications of AAS as antimicrobial agents, drug delivery vehicles, and a promising alternative to viral vectors in gene therapy.