pH-Induced Biophysical Perspectives of Binding of Surface-Active Ionic Liquid [BMIM][OSU] with HSA and Dynamics of the Formed Complex.

The influence of pH on the human serum albumin (HSA) interaction with ionic liquid (IL)1-butyl 3-methylimidazolium octyl sulfate ([BMIM][OSU]) at its sub-micellar concentration of 5 mM (well below CMC ∼31 mM at 25 °C) in aqueous solution has been monitored employing different methods, viz., circular dichroism (CD), fluorescence, electrokinetic determination of the zeta potential (ZP), nuclear magnetic resonance (NMR), small-angle neutron scattering (SANS), and molecular docking (MD). CD analysis indicated a noticeable reduction of the α-helical content of HSA by IL at pH 3. A significant interaction of the anionic part of IL with HSA was evident from the 1H chemical shifts and saturation transfer difference (STD) NMR. A strong binding between IL and HSA was observed at pH 3 relative to pH 5, revealing the importance of electrostatic and hydrophobic interactions assessed from global binding affinities and molecular correlation times derived from STD NMR and a combined selective/nonselective spin-relaxation analysis, respectively. ZP data supported the electrostatic interaction between HSA and the anionic part of IL. The nature of IL self-diffusion with HSA was assessed from the translational self-diffusion coefficients by pulse field gradient NMR. SANS results revealed the formation of prolate ellipsoidal geometry of the IL-HSA complex. MD identified the preferential binding sites of IL to the tryptophan centers on HSA. The association of IL with HSA was supported by fluorescence measurements, in addition to the structural changes that occurred in the protein by the interaction with IL. The anionic part of IL contributed a major interaction with HSA at the pH levels of study (3, 5, 8, and 11.4); at pH > 8 (effectively 11.4), the protein also interacted weakly with the cationic component of IL.

Effects of secondary carbon supplement on biofilm-mediated biodegradation of naphthalene by mutated naphthalene 1, 2-dioxygenase encoded by Pseudomonas putida strain KD9.

Polycyclic aromatic hydrocarbons (PAHs) belong to a diverse group of environmental pollutants distributed ubiquitously in the environment. The carcinogenic properties of PAHs are the main causes of harm to human health. The green technology, biodegradation have become convenient options to address the environmental pollution. In this study, we analyzed the biodegradation potential of naphthalene with secondary carbon supplements (SCSs) in carbon deficient media (CSM) by Pseudomonas putida strain KD9 isolated from oil refinerary waste. The rigid-flexible molecular docking method revealed that the mutated naphthalene 1,2-dioxygenase had lower affinity for naphthalene than that found in wild type strain. Moreover, analytical methods (HPLC, qRT-PCR) and soft agar chemotaxis suggest sucrose (0.5 wt%) to be the best chemo-attractant and it unequivocally caused enhanced biodegradation of naphthalene (500 mg L-1) in both biofilm-mediated and shake-flask biodegradation methods. In addition, the morphological analysis detected from microscopy clearly showed KD9 to change its size and shape (rod to pointed) during biodegradation of naphthalene in CSM as sole source of carbon and energy. The forward versus side light scatter plot of the singlet cells obtained from flow cytometry suggests smaller cell size in CSM and lower florescence intensity of the total DNA content of cells. This study concludes that sucrose may be used as potential bio-stimulation agent.

Physicochemical Understanding of Self-Aggregation and Microstructure of a Surface-Active Ionic Liquid [C4mim] [C8OSO3] Mixed with a Reverse Pluronic 10R5 (PO8EO22PO8).

Physicochemical studies on aqueous mixtures of ionic liquids (ILs) and reverse pluronics are limited. Self-aggregation dynamics and microstructure of a surface-active IL (SAIL), 1-butyl-3-methylimidazolium octylsulfate [C4mim] [C8OSO3], in the presence of a reverse pluronic, PO8EO22PO8 (known as 10R5), were studied using isothermal titration calorimetry (ITC), high-resolution nuclear magnetic resonance (NMR), and small-angle neutron scattering (SANS) methods. Also, cryo-/freeze-fracture transmission electron microscopy was employed to determine the microstructures of SAIL/10R5 mixtures. The ITC and NMR results revealed facilitation of SAIL aggregation in the presence of 10R5 forming mixed aggregates as well as free SAIL micelles. 2H spin relaxation rate data pointed out the onset of slow dynamics of the aqueous SAIL/10R5 mixture with an increase in either the former or the latter. Globular morphologies of the mixed species as well as their individual components were corroborated from the measurements. The preferential location of interaction of the SAIL with the 10R5 was identified from 13C NMR chemical shift findings to be in the interfacial region of the assembled SAIL. The formed species were mixed interacted aggregates but not mixed micelles that arise from mixed surfactants. The physicochemical information acquired herein would enrich the literature on the 10R5/SAIL mixed microheterogeneous systems having importance in the making of useful green drug carrier systems and templates for the synthesis of nanomaterials.

Understanding the effect of size and shape of gold nanomaterials on nanometal surface energy transfer.

Gold Nanomaterials (GNMs) interact with fluorophores via electromagnetic coupling under excitation. In this particular work we carried out (to the best of our knowledge for the first time) a comprehensive study of systematic quenching of a blue emitter 2-Anthracene Sulfonate (2-AS) in the presence of gold nanoparticles of different size and shape. We synthesized gold nanomaterials of four different dimensions [nanoparticle (0D), nanorod (1D), nanotriangle (2D) and nanobipyramids (3D)] and realized the underlying effect on the emitting dipole in terms of steady and time resolved fluorescence. Nanometal Surface Energy Transfer (NSET) has already been proved to be the best long range spectroscopic ruler so far. Many attempts have been made to understand the interaction between a fluorescent molecule and gold nanomaterials. But not a single model can interpret alone the interaction phenomena. We have opted three different models to compare the experimental and theoretical data. Due to the presence of size dependent absorptivity and dielectric function, modified CPS-Kuhn model was proved to be the worthiest to comprehend variance of behavior of an emitting dipole in close proximity to nanometal surface by coupling with the image dipole of gold nanomaterials.

Internal charge transfer based ratiometric interaction of anionic surfactant with calf thymus DNA bound cationic surfactant: Study I.

Cetyl trimethyl ammonium bromide (CTAB) binds calf thymus (ct-) DNA like anionic biopolymers electrostatically and established equilibrium both in the ground as well as in excited state in aqueous medium at pH 7. Anionic sodium dodecyl sulfate (SDS) does not show even hydrophobic interaction with ct-DNA at low concentration. On contrary, SDS can establish well defined equilibrium with DNA bound CTAB in ground state where the same CTAB-DNA isosbestic point reappears. First report of internal charge transfer (ICT) based binding of CTAB with ct-DNA as well as ICT based interaction of anionic SDS with DNA bound CTAB that shows dynamic quenching contribution also. The reappearance of anodic peak and slight increase in cathodic peak current with increasing concentration (at lower range) of anionic SDS, possibly reflect the release of CTAB from DNA bound CTAB by SDS.

Lacidipine self-nanoemulsifying drug delivery system for the enhancement of oral bioavailability.

Low bioavailability of Lacidipine (LD), an calcium channel blocker pose many challenges in the treatment of hypertension. The objective of this study was to formulate and characterize LD self-nanoemulsifying drug delivery systems (SNEDDS) to improve oral bioavailability of the drug. Formulations were evaluated for globule size, surface morphology, emulsification time, cloud point, drug content, in vitro dissolution, ex vivo permeation, stability and oral bioavailability studies. Captex 810D, TPGS, Tween-60, Transcutol P and PEG 400 was selected based on the solubility study results. The optimized SNEDDS readily gets nanoemulsified at 37 °C with droplet size of 41 nm when mixed with 200 times of its water. Transmission electron microscope photographs confirmed the spherical shape of the globules. In vitro dissolution of SNEDDS showed more than 80% of drug release within 15 min. The ex vivo permeation of LD from SNEDDS is 4.8- and 9-fold higher compared to pure drug in the absence and presence of verapamil respectively. The stability study of the SNEDDS confirmed no environmental effect on the physical nature and drug content. Oral bioavailability of SNEDDS is 2.5 times higher than marketed tablet. The results suggest that, the SNEDDS formulation can be used as a possible alternative for the traditional oral formulations of LD to improve its oral bioavailability.

Deciphering the Role of the Length of the Corona in Controlled NSET within Triblock Copolymers.

Nanometal surface energy transfer (NSET) from 2-anthracene sulfonate (2-AS) to gold nanoparticles in water-soluble triblock copolymers (TBP) P123 (PEO19PPO69PEO19) and F127 (PEO100PPO65PEO100) is systematically investigated. Fluorescence lifetime and anisotropy experiments provide thorough information on the locations of the 2-AS within these micelles. Variation in the size of the micellar corona region of the TBP is found to be the prime factor for different positions of 2-AS in them. Of late, nanometal surface energy transfer (NSET) from the donor probe to the surface of the metal nanoparticles has emerged as a potential tool for sensing and biolabeling. In the present work, the quenching of emission of the water-soluble 2-AS confined in the two different triblock copolymers in the proximity of a monolayer of the gold nanoparticles has been explored. Closer agreement between the experimental and theoretical characteristic distances has been found across the full wavelength range by the NSET approach. Understanding the location of the water-soluble dye in the vicinity of a polymeric drug delivery system is of significant importance, and how altered locations can trigger different controlled energy transfer efficiency from the 2-AS to the surfaces of gold nanoparticles (GNPs) has been discussed. This strategy could offer a new prospect in designing novel optical materials for chemical sensing and light harvesting endeavors.

Topical delivery of celecoxib using microemulsion.

The topical delivery of celecoxib has been studied using microemulsion as the vehicle for the treatment of UV B induced skin cancer. Pseudotemary phase diagrams were constructed at different oil to cosurfactant ratios to identify the formulation variables for microemulsion formation, and the effect of these variables on skin permeation of celecoxib was evaluated with excised rat skin. Topical anti-inflammatory effect of celecoxib has been assessed using the arachidonic acid induced ear oedema model. Formulation E consisting of 3% celecoxib, 22% propylene glycol dicaprylate/dicaprate + caprylic/capric mono-/di-glycerides (2:1), 30% polysorbate 80 and water (all w/w) showed higher permeation rate and significant anti-inflammatory activity. The studied microemulsion formulations have a prospect for use as a potential vehicle for treatment of UV B induced skin cancer.

Micellization of cetyltrimethylammonium bromide: effect of small chain Bola electrolytes.

Sodium dicarboxylates (or Bola salts) with methylene spacers 0, 2, 4, 6, 8, and 10 were studied in aqueous solution to investigate their influence on the micellization of cetyltrimethylammonium bromide (CTAB). Since bolas with spacer length ≤12 are known not to micellize in general, the herein used sodium dicarboxylates were treated as 2:1 amphiphilic electrolytes which reduced surface tension of water (except sodium oxalate with zero spacer) without self-association. Their concentration dependent conductance was also linear without breaks. The bolas affected the micellization of CTAB but acted like salts to decrease its CMC. Their combinations did not form bilayer aggregates as found in vesicles. Nevertheless, they synergistically interacted with CTAB at the air/water interface as revealed from Rosen's thermodynamic model. Hydrodynamic radius (Rh), Zeta-potential (ζ), and electrical double layer behavior of bola interacted CTAB micelles were assessed. From SANS measurements, micelle shape, shape parameters, aggregation number (Nagg), surface charge of the bola influenced CTAB micelles were also determined. NMR study as well supported the non-mixing of bolas with the CTAB micelles. They interacted in solution like "amphiphilic electrolytes" to influence the surface and micelle forming properties of CTAB.

Self-aggregation of MEGA-9 (N-nonanoyl-N-methyl-D-glucamine) in aqueous medium: physicochemistry of interfacial and solution behaviors with special reference to formation energetics and micelle microenvironment.

Self-aggregation of MEGA-9 (N-nonanoyl-N-methyl-D-glucamine), a nonionic sugar-based surfactant, was studied with respect to the effect of salt (NaCl) and ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate) on its critical micelle concentration (cmc), aggregation number, hydrodynamic dimensions, energetics of micellization, and micellar microenvironment. Fluorimetry (both steady state and time resolved) was used to understand the microenvironments under the influence of additives. NaCl was found to decrease cmc, increase aggregation number (N), increase micellar size, and decrease enthalpy of micelle formation; the IL effect on the parameters was mostly opposite. The microscopic properties of micelles were probed using two fluorophores: one nonpolar C-153 (2,3,5,6-1H,4H-tetrahydro-8-trifluormethylquinolizino-(9,9a,1-gh)coumarin) and the other fairly polar ANS (8-anilinonaphthalene-1-sulfonate); they delivered information on the palisade layer and the peripheral region of the micelle interface, respectively. Energy of activation and entropy of activation of the dynamics of the probes were evaluated from their decay time, lifetime, and rotational movements in the regions of residency in the micelles. Density functional theory (DFT) calculations showed that the ternary combination MEGA-9/IL/H2O had the maximum interaction energy compared to any of the binary combinations. Thus, the ionic liquid reduced MEGA-9 self-association to a large extent.

Formulation and physicochemical characterization of microemulsion system using isopropyl myristate, medium-chain glyceride, polysorbate 80 and water.

The phase behavior of the system isopropyl myristate/medium-chain glyceride/polysorbate 80/water forming both w/o and o/w microemulsions has been studied to develop microemulsion comprising of pharmaceutical excipients. The pseudo-ternary phase diagrams with large monophasic zones and gel formation were realized and several compositions were identified in the phase diagram for rheological, dynamic light scattering (DLS) and calorimetric measurements. The identified systems at different temperatures behaved as Newtonian fluid and the activation parameters for their viscous flow were evaluated. From DLS measurements, hydrodynamic diameter, polydispersity and diffusion coefficient of the microheterogeneous dispersions were determined. The free energy, enthalpy and entropy of solution of the w/o and o/w microemulsions were determined from calorimetric measurements.

Adsorption Behaviors of L-Histidine and DL-Tryptophan on Cholesterol, Silica, Alumina, and Graphite.

The adsorption of L-histidine (L-His) and DL-tryptophan (DL-Trp) on cholesterol, silica, alumina, and graphite surfaces from aqueous solution at pH 9.2 has been studied in the temperature range of 25 to 50 degrees C. The data have been analyzed, wherever applicable, by Langmuir and Hill equations to obtain (1) the monolayer adsorption capacity (x(m)) and the equilibrium constant (k') for the adsorption and desorption processes and (2) the Hill coefficient (n) at different temperatures. The results of adsorption on different kinds of adsorbents have been compared. The energetic parameters for the adsorption process have also been evaluated and compared. Copyright 2001 Academic Press.

Formulation design of self-microemulsifying drug delivery systems for improved oral bioavailability of celecoxib.

Celecoxib is a hydrophobic and highly permeable drug belonging to class II of biopharmaceutics classification system. Low aqueous solubility of celecoxib leads to high variability in absorption after oral administration. Cohesiveness, low bulk density and compressibility, and poor flow properties of celecoxib impart complications in it's processing into solid dosage forms. To improve the solubility and bioavailability and to get faster onset of action of celecoxib, the self-microemulsifying drug delivery system (SMEDDS) was developed. Composition of SMEDDS was optimized using simplex lattice mixture design. Dissolution efficiency, t(85%), absorbance of diluted SMEDDS formulation and solubility of celecoxib in diluted formulation were chosen as response variables. The SMEDDS formulation optimized via mixture design consisted of 49.5% PEG-8 caprylic/capric glycerides, 40.5% mixture of Tween20 and Propylene glycol monocaprylic ester (3:1) and 10% celecoxib, which showed significantly higher rate and extent of absorption than conventional capsule. The relative bioavailability of the SMEDDS formulation to the conventional capsule was 132%. The present study demonstrated the suitability of mixture design to optimize the compositions for SMEDDS. The developed SMEDDS formulations have the potential to minimize the variability in absorption and to provide rapid onset of action of celecoxib.

Anchor dependency for non-glycerol based cationic lipofectins: mixed bag of regular and anomalous transfection profiles.

Although detailed structure-activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure-activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1-15) of recently reported non-glycerol based monocationic transfection lipids. The C(14) analogues in both series 1 (lipids 1-6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C(12) analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C(10) and C(14) analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure-activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane reorganizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1-15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37 degrees C).