A Mechanistic Study to Determine the Structural Similarities Between Artificial Membrane Strat-M™ and Biological Membranes and Its Application to Carry Out Skin Permeation Study of Amphotericin B Nanoformulations.

Type of biological membrane used in skin permeation experiment significantly affects skin permeation and deposition potential of tested formulations. In this study, a comparative study has been carried out to evaluate the potential of a synthetic membrane (Strat-M™) with rat, human, and porcine ear skin to carry out skin permeation study of nanoformulations of a high molecular weight drug, amphotericin B. Results demonstrated that the permeation of this high molecular weight drug through Strat-M™ showed close similitude to human skin. Value of correlation coefficient (R2) of log diffusion between Strat-M™ and human skin was found to be 0.99 which demonstrated the similarities of Strat-M™ membrane to the human skin. In similarity factor analysis, the value of f2 was also found to be 85, which further demonstrated the similarities of Strat-M™ membrane to human skin. Moreover, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Brunauer-Emmett-Teller (BET) analysis of synthetic and biological membranes depicted almost similar morphological features (thickness, pore size, surface morphology, and diameter) of synthetic membrane with human skin. The results of the study demonstrated Strat-M™ as a better alternative to carry out skin permeation experiment due to the consistent results, reproducibility, easy availability, and minimum variability with human skin.

Nicotine-based surface active ionic liquids: Synthesis, self-assembly and cytotoxicity studies.

New ester-functionalized surface active ionic liquids (SAILs) based on nicotine, [CnENic][Br] (n=8, 10 and 12), with bromide counterions have been synthesized, characterized and investigated for their self-assembly behavior in aqueous medium. Conductivity measurements in aqueous solutions of the investigated SAILs have provided information about their critical micelle concentration (cmc), and degree of counterion binding (ß), where cmc was found to be 2-3-fold lower than homologous SAILs or conventional cationic surfactants. The inherent fluorescence of SAILs in the absence of any external fluorescent probe have shed light on cmc as well as interactions prevailing between the monomers in micelle at molecular level. The thermodynamic parameters related to micellization have been deduced from isothermal titration calorimetry (ITC) and conductivity measurements. 1H NMR, spin-lattice (T1) relaxation time and 2D 1H-IH ROESY measurements have been exploited to get detailed account of internal structure of micelle. The size and shape of the micelles have been explored using dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. The synthesized SAILs have been found to be non-cytotoxic towards C6-Glioma cell line, which adds to the possible utility of these SAILs for diverse biological applications.

Structural diversity, physicochemical properties and application of imidazolium surfactants: Recent advances.

The current review covers recent advances on development and investigation of cationic surfactants containing imidazolium headgroup, which are being extensively investigated for their self-aggregation properties and are currently being utilized in various conventional and non-conventional application areas. These surfactants are being used as: soft template for synthesis of mesoporous/microporous materials, drug and gene delivery agent, stabilizing agent for nanoparticles, dispersants for single/multi walled carbon nanotubes, antimicrobial and antifungal agent, viscosity modifiers, preparing nanocomposite materials, stabilizing microemulsions, corrosion inhibitors and catalyst for organic reactions. Recently several structural derivatives of these surfactants have been developed having many interesting physicochemical properties and they have demonstrated enormous potential in the area of nanotechnology, material science and biomedical science.

Aggregation behavior of non-cytotoxic ester functionalized morpholinium based ionic liquids in aqueous media.

Ester functionalized surface active ionic liquids (SAILs), [CnEMorph][Br], where n=8, 12 and 16, comprising of long hydrophobic chain appended with ester functionality connected to N-methylmorpholine group have been synthesized and investigated for their aggregation behavior and cytotoxicity. A variety of state of art techniques viz. tensiometry, conductometry, isothermal titration calorimetry (ITC), spectrofluorometry, dynamic light scattering (DLS) and atomic force microscopy (AFM) have been employed to get insight into the various aspects of aggregation behavior. The investigated SAILs have been found to possess lower critical aggregation concentration (cac) and greater adsorption efficacy at air-solution interface as compared to earlier reported non-functionalized SAILs or conventional ionic surfactants. Further, the thermal stability of these morpholinium cationics has been evaluated by thermal gravimetric analysis (TGA). These SAILs have been found to be non-cytotoxic in the concentration range generally required for different biological applications as judged by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on the C6 glioma cell line. The dependence of characteristic properties of aggregation on alkyl chain length has been established.

Self-assembly and biophysical properties of gemini 3-alkyloxypyridinium amphiphiles with a hydroxyl-substituted spacer.

New gemini pyridinium amphiphiles having alkyl chain lengths of C10, C12, C14 , and C16 and appended with hydroxyl-substituted spacers have been synthesized, characterized, and investigated for their self-assembly as well as adsorption behavior by state-of-the-art techniques such as conductometry, tensiometry, isothermal titration calorimetry (ITC), and spectrofluorometry. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) have provided excellent acumen with respect to the micellar size distribution of investigated dicationics in aqueous media. Furthermore, the interaction of these dicationics with plasmid DNA, at different charge ratios (N/P), has been studied by DLS, agarose gel electrophoresis, and ethidium bromide exclusion measurements. The cytotoxicity of these geminis has been evaluated by using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on BV2 (microglial) and C6 glioma cell lines. It was found that the varying alkyl chain length, fashioned by ether linkage close to the headgroup, and the presence of a polar linker significantly altered the physicochemical properties of these new dicationics as compared to the properties of nonfunctionalized gemini surfactants.

Effect of cationic head group on micellization behavior of new amide-functionalized surface active ionic liquids.

Amide-functionalized surface active ionic liquids (SAILs), 1-methyl-1-dodecyl piperidinium chloride, [C12APip][Cl]; 1-methyl-1-dodecyl pyrrolidinium chloride, [C12APyrr][Cl]; 1-methyl-3-dodecyl imidazolium chloride, [C12Amim][Cl], and 1-methyl-1-dodecyl morpholinium chloride, [C12AMorph][Cl], have been synthesized, characterized and investigated for thermal stability, and micellization behavior in aqueous medium. The introduction of an amide moiety in the alkyl chain decreased the thermal stability of the functionalized SAILs compared to non-functionalized SAILs bearing a simple alkyl chain. A variety of state of the art techniques, viz. tensiometry, conductometry, steady-state fluorescence, isothermal titration calorimetry (ITC), dynamic light scattering (DLS) and atomic force microscopy (AFM), have been employed to investigate the micellization behavior. Amide-functionalized SAILs have shown much lower critical micelle concentration, cmc, and better surface active properties as compared to homologous non-functionalized SAILs. Steady-state fluorescence has provided information about cmc, aggregation number (Nagg) and polarity of the cybotactic region of the micelles, whereas ITC has provided insights into the thermodynamics of micellization. Furthermore, the size and shape of the micelles have been investigated using DLS and AFM techniques.

Synthesis and bio-physicochemical properties of amide-functionalized N-methylpiperazinium surfactants.

Four new amide functionalized N-methylpiperazinium amphiphiles having tetradecyl, hexadecyl alkyl chain lengths and counterions; chloride or bromide have been synthesized and characterized by various spectroscopic techniques. These new surfactants have been investigated in detail for their self-assembling behavior by surface tension, conductivity and fluorescence measurements. The thermodynamic parameters of these surfactants indicate that micellization is exothermic and entropy-driven. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) experiments have been performed to insight the aggregate size of these cationics. Thermal degradation of these new surfactants has also been evaluated by thermal gravimetric analysis (TGA). These new surfactants form stable complexes with DNA as acknowledged by agarose gel electrophoresis, ethidium bromide exclusion and zeta potential measurements. They have also been found to have low cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on the C6 glioma cell line.

Micellization behavior of morpholinium-based amide-functionalized ionic liquids in aqueous media.

Morpholinium-based amide-functionalized ionic liquids (ILs) [C(n)AMorph][Br], where n = 8, 12, and 16, have been synthesized and characterized for their micellization behavior in aqueous medium using a variety of state of the art techniques. The adsorption and micellization behavior of [CnAMorph][Br] ILs at the air-solution interface and in the bulk, respectively, has been found to be much better compared to that observed for nonfunctionalized homologous ILs and conventional cationic surfactants, as shown by the comparatively higher adsorption efficiency, lower surface tension at the critical micelle concentraiton (γ(cmc)), and much lower critical micelle concentration (cmc) for [C(n)AMorph][Br] ILs. Conductivity measurements have been performed to obtain the cmc, degree of counterion binding (ß), and standard free energy of micellization (ΔG(m)°). Isothermal titration calorimetry has provided information specifically about the thermodynamics of micellization, whereas steady-state fluorescence has been used to obtain the cmc, micropolarity of the cybotactic region, and aggregation number (N(agg)) of the micelles. Both dynamic light scattering and atomic force microscopy have provided insights into the size and shape of the micelles. 2D (1)H-(1)H nuclear Overhauser effect spectroscopy experiments have provided insights into the structure of the micelle, where [C16AMorph][Br] has shown distinct micellization behavior as compared to [C8AMorph][Br] and [C12AMorph][Br] in corroboration with observations made from other techniques.

Self-assembly, DNA binding and cytotoxicity trends of ether functionalized gemini pyridinium amphiphiles.

Six new ether functionalized gemini pyridinium amphiphiles have been synthesized having dodecyl, tetradecyl alkyl chain lengths and three different spacers (i.e. -(CH2)n-, where n is 4, 5 and 6) and investigated for their self-assembling behavior by state of the art techniques such as tensiometry, conductivity and spectrofluorometry. These new pyridinium gemini surfactants exhibit lower cmc values as compared to other gemini surfactants reported in literature. These amphiphiles form stable complexes with DNA as established by agarose gel electrophoresis and ethidium bromide exclusion experiments. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was carried out in vitro on C6 glioma cell line for cytotoxicity assessment of new pyridinium geminis. The dynamic light scattering (DLS) and transmission electron microscopy (TEM) have been used to measure the micellar size of gemini surfactants. Further, thermal stability of these amphiphiles has been evaluated by thermogravimetric analysis (TGA). The dependence of self-assembly behavior and other properties on spacer as well as alkyl chain length has been established.

Gemini imidazolium surfactants: synthesis and their biophysiochemical study.

New gemini imidazolium surfactants 9-13 have been synthesized by a regioselective epoxy ring-opening reaction under solvent-free conditions. The surface properties of these new gemini surfactants were evaluated by surface tension and conductivity measurements. These surfactants have been found to have low critical micelle concentration (cmc) values as compared to other categories of gemini cationic surfactants and also showed the tendency to form premicellar aggregates in solution at sufficiently low concentration below their cmc values. The thermal degradation of these surfactants was determined by thermograviometry analysis (TGA). These new cationic surfactants have a good DNA binding capability as determined by agarose gel electrophoresis and ethidium bromide exclusion experiments. They have also been found to have low cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on the C6 glioma cell line.

Physicochemical studies of pyridinium gemini surfactants with promethazine hydrochloride in aqueous solution.

The mixed micellization and interfacial behavior of pyridinium gemini surfactants, 1,1'-(1,1'-(ethane-1,2-diylbis-(sulfanediyl))bis(alkane-2,1-diyl))dipyridinium bromide, i.e., [12-(S-2-S)-12], [14-(S-2-S)-14], [16-(S-2-S)-16] with a phenothiazine tranquilizer drug, promethazine hydrochloride (PMT), has been investigated by conductivity, surface tension and steady state fluorescence measurements. Different spectroscopic techniques like fluorescence, UV-visible and NMR were also employed to understand the nature of interactions between the pyridinium gemini surfactants and PMT. The various micellar, interfacial and associated thermodynamic parameters for different mole fractions of PMT-pyridinium gemini surfactant mixtures have been evaluated. Synergism was observed in the mixed micelle as well as the monolayer formed by these mixtures. The fluorescence quenching experiment indicates that the interactions between PMT and surfactants are hydrophobic in nature. The UV-visible measurements reveal the distinct formation of a drug-surfactant complex. The detailed mechanism for the type of interactions was further studied by NMR titrations which show cation-π interactions between PMT and pyridinium gemini surfactant molecules.

Synthesis and properties of thioether spacer containing gemini imidazolium surfactants.

Twelve new gemini imidazolium surfactants have been synthesized, having dodecyl, tetradecyl, hexadecyl, and octadecyl chain lengths and three different spacers (i.e., -S-(CH(2))(n)-S-), where n = 2, 3, and 4 and their surface properties have been evaluated by surface tension and conductivity methods. The thermal degradation of these new gemini surfactants was determined by thermogravimetric analysis (TGA). These surfactants have low cmc values as compared to other categories of gemini cationic surfactants and exhibit peculiarities at sufficiently low concentration because they were able to form premicellar aggregates over a wide range of concentration below their cmc values. The DNA binding affinity of these gemini surfactants determined by agarose gel electrophoresis and ethidium bromide exclusion experiments established their strong interaction with DNA, thereby protecting it against enzymatic degradation.

Synthesis, characterization and comparative evaluation of phenoxy ring containing long chain gemini imidazolium and pyridinium amphiphiles.

Two series of phenoxy ring containing long chain imidazolium and pyridinium based gemini amphiphiles have been synthesized from renewable cardanol oil having different spacers (i. e. -S-(CH(2))(n)-S-, where n is 2, 3, 4 & 6). Critical micelle concentration (cmc) of these new gemini amphiphiles has been determined by conductivity method. Further, these new cationic amphiphiles have been evaluated for their DNA binding capability by agarose gel electrophoresis, ethidium bromide exclusion experiments and transmission electron microscopy (TEM). The cytotoxicity of these new amphiphiles have been evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Comparative studies of these phenoxy ring containing long chain gemini imidazolium amphiphiles and their pyridinium analogues depicted low cmc values of the later but greater DNA interaction capability and low cytotoxicity of the former series of amphiphiles.

Novel gemini pyridinium surfactants: synthesis and study of their surface activity, DNA binding, and cytotoxicity.

New pyridinium gemini amphiphiles having ethane-1,2-dithiol spacer have been synthesized by regioselective electrophilic cobromination of alpha-olefins. Ethane-1,2-dithiol (1) and N-bromosuccinimide (6) on reaction with alpha-olefins (dodecene (2), tetradecene (3), hexadecene (4), and octadecene (5)) gave the respective 1,2-bis(2-bromoalkylthio)ethane (7-10). The bromoalkylthio ethers when reacted with pyridine (11) gave the respective gemini bispyridinium bromide (12-15). The surface properties of new geminis were evaluated by surface tension and conductivity measurements. These gemini surfactants have also been found to be having low cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on C6 glioma cells. The DNA binding capabilities of these amphiphiles have been determined below as well as above critical micelle concentration. The preliminary studies by agarose gel electrophoresis indicated chain length dependent DNA binding abilities which has further been proved by ethidium bromide exclusion experiments and transmission electron microscopy (TEM).