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A series of β-amino acid containing tripeptides has been designed and synthesized in order to develop oligopeptide-based, thermoreversible, pH-sensitive, and proteolytically stable hydrogels. The Fmoc [N-(fluorenyl-9-methoxycarbonyl)]-protected tripeptides were found to produce hydrogels in both pH 7 and 2 buffers at a very low concentration (<0.2% w/v). It has been shown that the Fmoc group plays an important role in the gelation process. Also a dependence of gelation ability on hydrophobicity of the side chain of the Fmoc-protected α-amino acid was observed. The effect of the addition of inorganic salts on the gelation process was investigated as well. Spectroscopic studies indicated formation of J-aggregates through π-π stacking interactions between Fmoc groups in solution as well as in the gel state. In the gel phase, these self-assembling tripeptides form long interconnected nanofibrils leading to the formation of 3-dimensional network structure. The hydrogels were characterized by various techniques, including field emission electron microscopy, transmission electron microscopy, atomic force microscopy, rheology, Fourier transform IR, circular dichroism (CD), and wide-angle X-ray diffraction (WAXD) spectroscopy. The CD studies and WAXD analyses show an antiparallel β-sheet structure in the gel state. l-Phenylalanine and l-tyrosine containing tripeptides formed helical aggregates with handedness opposite to those containing l-valine and l-leucine residues. The mechanical stability of the hydrogels was found to depend on the hydrophobicity of the side chain of the tripeptide as well as on the pH of the solution. Also, the tripeptides exhibit in vitro proteolytic stability against proteinase K enzyme. [ABSTRACT FROM AUTHOR]

In our recent reports, we have shown that when a poly(ethylene glycol) (PEG) chain is covalently linked to any ionic group, the resultant molecule behaves like an amphiphile. Depending upon the nature of ionic head groups, they self-assemble to form micelles or vesicles, in which the PEG chain constitutes the micellar core or vesicle bilayer. In this study, we intend to examine what happens when both hydrocarbon (HC) and PEG chains are attached to a carboxylate head group. Therefore, we have synthesized two novel amphiphiles in which a PEG and a HC chain is covalently linked to l-cysteine. The surface activities and the solution behavior of the sodium salts of these amphiphiles were investigated at neutral pH. The amphiphiles self-organize to form large unilamellar vesicles in dilute solutions, which transformed into small micelles at higher concentrations. The HC chains of the molecules have been shown to constitute the bilayer membrane of the vesicles and core of micelles. In acidic pH, the amphiphiles were found to form large disklike micelles. The thermodynamic parameters of self-assembly formation were also measured by isothermal titration calorimetry. The vesicle and micelle formation was found to be spontaneous and thermodynamically favorable. The thermal stability of the micelles at neutral and acidic pH was studied. The addition of cholesterol was observed to increase the physical stability of vesicles. [ABSTRACT FROM AUTHOR]

Thestudy of protein–surfactant interactions is importantbecause of the widespread use of surfactants in industry, medicine,and pharmaceutical fields. Sodium N-lauroylsarcosinate(SL-Sar) is a widely used surfactant in cosmetics, shampoos. In thispaper, we studied the interactions of bovine serum albumin (BSA)with SL-Sar and sodium N-lauroylglycinate (SL-Gly)by use of a number of techniques, including fluorescence and circulardichroism spectroscopy and isothermal titration calorimetry. The bindingstrength of SL-Sar is stronger than that of structurally similar SL-Gly,which differs only by the absence of a methyl group in the amide nitrogenatom. Also, these two surfactants exhibit different binding patternswith the BSA protein. The role of the amide bond and hence the surfactantheadgroup in the binding mechanism is discussed in this paper. Itwas observed that while SL-Sar destabilized, SL-Gly stabilized theprotein structure, even at concentrations less than the critical micelleconcentration (cmc) value. The thermodynamics of surfactant bindingto BSA was studied by use of ITC. From the ITC results, it is concludedthat three molecules of SL-Sar in contrast to only one molecule ofSL-Gly bind to BSA in one set of binding sites at room temperature.However, on increasing temperature four molecules of SL-Gly bind tothe BSA through H-bonding and van der Waals interactions, due to looseningof the BSA structure. In contrast, with SL-Sar the binding processis enthalpy driven, and very little structural change of BSA was observedat higher temperature. [ABSTRACT FROM AUTHOR]

A series ofN-(n-alkylcarbamoyl)-l-amino acid amphiphiles with different amino acid head groups were designed and synthesised. The gelation abilities of these amphiphilic molecules were studied in toluene andp-xylene solvents. The hypothesis that steric crowding at the chiral head group destroys gelation ability of the amphiphile was examined. Indeed, besidel-alanine-based amphiphile, onlyl-serine andl-aspartic acid derivatives were found to gelate the organic liquids efficiently in the presence of a small quantity of water. The gels were characterised by a number of methods, including FT-IR, NMR and X-ray diffraction spectroscopy, scanning electron microscopy (SEM) and rheology. The SEM micrographs revealed three-dimensional networks of ribbon-like aggregates. The organogels were observed to be thermo-reversible in nature and have sufficient mechanical strength. The gels have gel-to-sol transition temperatures above the physiological temperature (310 K). [ABSTRACT FROM AUTHOR]

Two new l-cysteine-derivedzwitterionic amphiphiles withpoly(ethylene glycol) methyl ether (mPEG) tail of different chainlengths were synthesized and their surface activity and self-assemblyproperties were investigated. In aqueous phosphate buffered solutionof pH 7.0, the amphiphiles were observed to form stable unilamellarvesicles, the bilayer membrane of which is constituted by the mPEGchains. The vesicle phase was characterized by a number of methodsincluding fluorescence spectroscopy, dynamic light scattering, andtransmission electron microscopy. The thermodynamics of self-assemblywas also studied by isothermal titration calorimetry through measurementsof the standard Gibbs free energy change (ΔG°m), standard enthalpy change (ΔH°m) and standard entropy change (ΔS°m) of micellization. The self-assembly process wasfound to be entropy-driven, which implies that the mPEG chain behaveslike a hydrocarbon tail of conventional surfactants. The effects ofpH, temperature, salt, and aging time on the bilayer stability werealso investigated. Encapsulation and pH-triggered release of modelhydrophobic and hydrophilic drugs is demonstrated. [ABSTRACT FROM AUTHOR]

The major driving force for organogelationis known to be hydrogenbonding for gelators containing functional groups capable of forminghydrogen bond(s). In order to examine this, we have investigated thegelation behavior of two 4-(N-tetradecanoyl)aminohydroxybutanoicacid amphiphiles in a series of organic solvents and compared withthose of the corresponding unsubstituted amphiphile 4-(N-tetradecanoyl)aminobutanoic acid (C14-ABA). The gelationability of the nonhydroxyl amphiphile C14-ABA was foundto be better than the hydroxyl group substituted amphiphiles. An attemptwas also made to correlate gelation abilities of the amphiphiles withthe solvent polarity parameters. The driving force for the gelationwas studied by Fourier transform infrared and 1H NMR spectroscopy.The organogels were characterized by electron microscopy and XRD.The thermal stability of the gels was investigated by measuring thesol-to-gel transition temperature. Rheological measurements were performedin order to determine the mechanical stability of the organogels.The gelation ability and thermal and mechanical stability of the organogelswere correlated with the intermolecular hydrogen-bonding interactionsbetween amphiphile head groups. [ABSTRACT FROM AUTHOR]

The delivery of drugs to the brain in the therapy of diseases of the central nervous system (CNS) remains a continuing challenge because of the lack of delivery systems that can cross the blood-brain barrier (BBB). Therefore, there is a need to develop an innovative delivery method for the treatment of CNS diseases. Thus, we have investigated the interaction of γ-aminobutyric acid (GABA) and S-(-)-γ-amino-α-hydroxybutyric acid (GAHBA) with the GABA receptor by performing a docking study. Both GABA and GAHBA show comparable binding affinities toward the receptor. In this study, we developed surface-modified solid lipid nanoparticles (SLNs) using GAHBA-derived lipids that can cross the BBB. CLB-loaded SLNs were characterized by a number of methods including differential scanning calorimetry, dynamic light scattering, UV-vis spectroscopy, and transmission electron microscopy. The blank and CLB-loaded SLN suspensions were found to exhibit good storage stability. Also, the SLNs showed a higher encapsulation efficiency for CLB drugs. In vitro release kinetics of CLB at physiological temperature was also investigated. The results of the in vitro cell cytotoxicity assay and flow cytometry studies in the human glioma U87MG cell line and human prostate cancer PC3 cell line suggested a higher efficacy of the GAHBA-modified CLB-loaded SLNs in U87MG cells. The transcription level of GABA receptor expression in the target organ and cell line was analyzed by a reverse transcription polymerase chain reaction study. The in vivo biodistribution and brain uptake in C57BL6 mice and SPECT/CT imaging in Wistar rats investigated using 99m Tc-labeled SLN and autoradiography suggest that the SLNs have an increasing brain uptake. We have demonstrated the delivery of the anticancer drug chlorambucil (CLB) to glioma.

Solid lipid nanoparticles (SLNs) are promising drug delivery vehicles for the delivery of various drugs, especially poorly water-soluble drugs. However, the aqueous stability, drug release, and biocompatibility of SLNs are some of the issues that need attention. In this work, curcumin-loaded SLNs were prepared, and morphology, particle size, and entrapment efficiency were studied. For this, two amino acid-derived lipids were developed. The effect of the polarity of the lipid head on the aqueous stability of the SLN dispersion was investigated. Based on the stability, particle size, and polydispersity, an optimum formulation was obtained. The curcumin entrapment efficiency of the SLNs was found to be greater than those reported in the literature. The entrapped curcumin, as well as curcumin-loaded SLN suspensions, exhibited improved storage stability. The in vitro release kinetics indicated an enhanced rate of drug release in the case of curcumin-loaded SLNs consisting of the lipid containing -OH groups at the lipid head. The pure lipid and the blank SLN were found to have no significant cytotoxicity, but curcumin and curcumin-loaded SLNs induced cell death in a concentration-dependent manner in both human prostatic adenocarcinoma PC3 cell line and human breast carcinoma MCF7 cell line. This study has proposed a potential semisynthetic lipid for the stable SLN suspension for the delivery of curcumin.