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The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy.

A general understanding of interactions between DNA and oppositely charged compounds forms the basis for developing novel DNA-based materials, including gel particles. The association strength, which is altered by varying the chemical structure of the cationic cosolute, determines the spatial homogeneity of the gelation process, creating DNA reservoir devices and DNA matrix devices that can be designed to release either single- (ssDNA) or double-stranded (dsDNA) DNA. This review covers recent developments on the topic of DNA gel particles formed in water-water emulsion-type interfaces. The degree of DNA entrapment, particle morphology, swelling/dissolution behavior and DNA release responses are discussed as functions of the nature of the cationic agent used. On the basis of designing DNA gel particles for therapeutic purposes, recent studies on the determination of the surface hydrophobicity and the hemolytic and the cytotoxic assessments of the obtained DNA gel particles have been also reported.

Surfactants are used as additives in topical pharmaceuticals and drug delivery systems. The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a reliable approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC(50)-values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry.

The design of efficient liposomal systems for drug delivery is of considerable biomedical interest. In this context, vesicles prepared from cationic/anionic surfactants may offer several advantages, mainly due to their spontaneity in formation and long-term stability. There is also an impending need to produce less toxic, more biocompatible amphiphiles, while maintaining the desirable aggregation properties. In this work, we present data for acute toxicity to Daphnia magna (IC(50)), and potential ocular irritation (HC(50)) for some newly prepared ionic surfactants with dodecyl chains, derived from the amino acids tyrosine (Tyr), serine (Ser), hydroxyproline (Hyp) and lysine (Lys). The micellization behavior of the compounds, evaluated from surface tension measurements, is presented and compared to more conventional ionic amphiphiles. Two types of spontaneouly formed catanionic vesicles, composed either by a dodecyltrimethylammonium bromide (DTAB)/Lys-derivative and or Ser-/Lys-derivative mixture, have also been tested for their ecotoxicity and hemolytic potential. All the micelle-forming surfactants as well as the vesicle-containing mixtures are found to have lower ecotoxicity than the reference surfactant DTAB. Moreover, the results from hemolysis and hemoglobin denaturation tests show that the Tyr- and Lys-derivatives are moderately irritant, whereas the Hyp- and Ser- ones are just slightly irritant. Even more significantly, the vesicle-containing mixtures exhibit lower hemolytic activity than the neat surfactants, a positive result for their potential use in liposomal formulations.

A protocol for the qualitative and quantitative analysis of novel arginine-based cationic surfactants using HPLC and CE was studied and compared. The optimization of the analytical conditions was carried out through a systematic variation of the experimental parameters such as mobile phase, eluent conditions, ion pairing and amount of sample for HPLC, and type of buffer, ion strength, type and amount of organic solvent, sample injection time, applied voltage and column washing and conditioning for CE.

Several lipoamino acids were synthesized in which palmitic acid was coupled with the alpha-amino group of an amino acid. These lipoamino acids were tested for their inhibitory action against Sendai virus fusion to liposomes composed of egg phosphatidylethanolamine and 5 mol% of the ganglioside GD1a. A commonly employed viral fusion assay based on the dilution of the fluorescent probe octadecylrhodamine (R18) exhibited an additional complication in the presence of Nalpha-palmitoyl tryptophan (palm-Trp). At higher mol fraction of palm-Trp it was observed that there was an increase in R18 quenching. Studies on the dependence of the emission wavelength of palm-Trp on excitation wavelength demonstrated that the presence of R18 alters the environment of the indole. The results illustrate one of the complexities of viral fusion assays using the R18 probe. Despite this complication it was possible to demonstrate that several of the lipoamino acids are effective at inhibiting the fusion of Sendai virus to liposomes as measured by the R18 assay. One of the most effective inhibitors of this process is palm-Trp which, at a concentration of 4 mol% in liposomes, markedly reduces the apparent rate of fusion. At pH 5.0 this amphiphile is also an inhibitor of Sendai virus fusion, indicating that the ionization of the carboxyl group of this amphiphile is not required for its antiviral activity. The inhibitory action of palm-Trp against Sendai virus was confirmed by demonstrating inhibition of Sendai-mediated cytopathic effects studied in tissue culture. A property associated with antiviral activity is the ability of amphiphiles to raise the bilayer to hexagonal phase transition temperature of dielaidoyl phosphatidylethanolamine. All of these lipoamino acids were found to possess this property, but a quantitative relationship with inhibition of viral fusion was not found.

Capillary zone electrophoresis was applied to the analysis of N-benzyl-N-alkyl-N,N-dimethylammonium chloride compounds with different alkyl chain lengths (C12-C18) by direct UV detection. A tetrahydrofuran-containing buffer was used to prevent the occurrence of micellization and adsorption of the surfactants, thereby yielding adequate separations according to their free-form electrophoretic mobilities. Resolution, theoretical plate number, reproducibility and precision were ascertained. Finally, the electrophoretic method was applied to the qualitative and quantitative determination of an industrial mixture of C(n)-benzyl surfactants.

Due to current trends, such as energy savings and the increase in environmental and toxicological concerns, at present there is a strong industrial need for high performance chemicals such as surfactants with biodegradable and biocompatible properties. One interesting and practical strategy concerns the preparation of surfactant molecules based on the design of molecular mimics of natural compounds such as lipoaminoacids, phospholipids and glycolipids. They are characterized by a non-conventional structure derived from amino acids, oligosaccarides and glycerols. This paper reviews the research results on structure, chemical preparation, properties and uses of lipoaminoacids and glycerolipids.

The equilibrium and dynamic tension behavior of aqueous DLPC was studied at 37 and 25°C at concentrations both below and above the solubility, from 0.00016 to 0.10 wt.%. For most systems examined, the equilibrium tension was about 25 mN m-1. The dispersed liposomes participate actively in the tension dynamics under constant or pulsating area conditions. At pulsation frequencies of 10-80 cycles min-1, and at around the area minimum, the tension can reach super-low (<10 mN m-1) tensions at 37°C but not at 25°C. This dynamic behavior correlates with a smaller adsorption rate at the lower temperature and a slightly different monolayer pressure-area isotherm.