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The aim of this work is to develop and characterize a formulation intended for the cutaneous administration of glutathione (γ-glutamylcysteinylglycine, GSH), potentially useful for cellular defense against UV-induced damage. For this purpose, liposomes containing GSH or GSH/cyclodextrins(CDs) inclusion complexes as well as liposomes dispersed within a hydrophilic gel, were evaluated. These formulations were designed in order to obtain a system combining the advantages of liposomes as vehicles for topical drug delivery with those of CDs as penetration enhancers. The studied CDs were the natural (β-CD) and chemically modified (i.e., HP-β-CD and CH3 -β-CD) cyclodextrins. The prepared liposomes showed homogeneous size distribution, mean diameter in the range 622-1435 nm, small positive charge (+3.1 to +6.6 mV), and encapsulation efficiency of the peptide in the range 13.6%-23.7%. Release studies showed that the presence of the oligosaccharide may influence to some extent the amount of drug released, whereas stability studies clearly point out that the incorporation in a hydrophilic gel of 2-hydroxyethylcellulose insures a stable formulation maintaining unchanged the characteristics of liposomal vesicles., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)

The aim of this work was to study the complexation capability of new sulfobutyl ether-alkyl ether (SBE-AE-CD) mixed beta- and gamma-cyclodextrin derivatives with a series of structurally related steroids (6alpha-methylprednisolone, prednisolone, triamcinolone, D(-) norgestrel and hydrocortisone) and a number of dihydropyridine calcium channel blockers (nimodipine, nitrendipine, nifedipine) that traditionally interact poorly with other cyclodextrins (CDs). The effect of the total degree of substitution (TDS) and of the length of the alkyl side chain on binding capacity of these new modified CDs was evaluated as was their ability to induce red blood cell hemolysis. An attempt was made to correlate hemolysis to surface activity. Binding constants between the SBE-AE-CDs and selected molecules were determined by spectroscopic studies, and only in few cases by solubility studies. Hemolysis percentage was determined using citrated rabbit blood and citrated human blood with UV analysis. The surface activity was measured with a tensiometer. A significant improvement in the binding capacity between various substrates and the new SBE-AE-CDs was observed when compared to the SBE-CDs. The length of the alkyl chain and total degree of alkylation affected the binding with the relationship being complex. For most compounds, an intermediate degree of substitution appeared to be advantageous. The hemolysis studies showed that some of the derivatives may induce hemolysis and this correlated with higher surface activity for some but not all of the derivatives., (2009 Wiley-Liss, Inc. and the American Pharmacists Association)

The objective of this study is to see if random alkyl ethers of various sulfoalkyl ether cyclodextrins can be synthesized and characterized. The purpose of the alkylation was to test the hypothesis that an increase in the "height" of a cyclodextrins cavity would help in the binding/complexation of larger more structurally complex molecules. The synthesis of new cyclodextrin derivatives comprising a mixture of sulfoalkyl ether and alkyl ether substituents on the same cyclodextrin ring was performed in aqueous alkaline solutions using various sultones and alkylsulfates. The method presented provided an easy and efficient way to modify cyclodextrins avoiding the use of organic solvents and high quantities of alkylating agents and could be carried out in either a two step or "one pot" single step process. Purification was by neutralization followed by ultrafiltration. The derivatives were characterized by 1D, ((1)H and (13)C), and a 2D NMR technique (HMQC, Heteronuclear Multiple Quantum Coherence). The combination of these techniques allowed an analysis of the degree of substitution and the site of substitution on the cyclodextrin (CD) nucleus. For both beta- and gamma-CD, sulfoakylation was preferred on the 2 > 3 > 6 hydroxyls while alkylation was preferred 6 > 2 > 3. Due to the simultaneous presence of short alkyl ether chains and negatively charged sulfoalkyl ether chains, these mixed water-soluble cyclodextrin derivatives, especially those of gamma-cyclodextrin, should be able to bind more complex drugs. The improved binding capacity of these new modified CDs with the model drug 6alpha-methylprednisolone is reported.