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Hydrophilic Layer (hydrophilic + layer)
Selected AbstractsInteraction of a ,-sheet breaker peptide with lipid membranesJOURNAL OF PEPTIDE SCIENCE, Issue 2 2010Giuseppe Vitiello Abstract Aggregation of ,-amyloid peptides into senile plaques has been identified as one of the hallmarks of Alzheimer's disease. An attractive therapeutic strategy for Alzheimer's disease is the inhibition of the soluble ,-amyloid aggregation using synthetic ,-sheet breaker peptides that are capable of binding A, but are unable to become part of a ,-sheet structure. As the early stages of the A, aggregation process are supposed to occur close to the neuronal membrane, it is strategic to define the ,-sheet breaker peptide positioning with respect to lipid bilayers. In this work, we have focused on the interaction between the ,-sheet breaker peptide acetyl-LPFFD-amide, iA,5p, and lipid membranes, studied by ESR spectroscopy, using either peptides alternatively labeled at the C- and at the N-terminus or phospholipids spin-labeled in different positions of the acyl chain. Our results show that iA,5p interacts directly with membranes formed by the zwitterionic phospholipid dioleoyl phosphatidylcholine and this interaction is modulated by inclusion of cholesterol in the lipid bilayer formulation, in terms of both peptide partition coefficient and the solubilization site. In particular, cholesterol decreases the peptide partition coefficient between the membrane and the aqueous medium. Moreover, in the absence of cholesterol, iA,5p is located between the outer part of the hydrophobic core and the external hydrophilic layer of the membrane, while in the presence of cholesterol it penetrates more deeply into the lipid bilayer. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] Bilayered nail lacquer of terbinafine hydrochloride for treatment of onychomycosisJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2010H.N. Shivakumar Abstract The present study aimed to develop bilayered nail lacquer of terbinafine hydrochloride (TH) for treatment of onychomycosis. The composite nail lacquer formed an underlying drug-loaded hydrophilic layer and overlying hydrophobic vinyl layer. The hydrophilic lacquer made of hydroxylpropyl methylcellulose E-15 contained polyethylene glycol 400 (PEG 400) as a drug permeation enhancer. The vinyl lacquer was composed of poly (4-vinyl phenol) as a water-resistant film former. In vitro permeation studies in Franz diffusion cells indicated that the amount of TH permeated across the human cadaver nail in 6 days was 0.32,±,0.14, 1.12,±,0.42, and 1.42,±,0.53,µg/cm2 from control (hydrophilic lacquer devoid of PEG 400), monolayer (hydrophilic lacquer alone), and bilayered nail lacquers, respectively. A higher nail drug load was seen in vitro with the bilayered lacquer (0.59,±,0.13,µg/mg) as compared to monolayer (0.36,±,0.09,µg/mg) and control (0.28,±,0.07,µg/mg) lacquers. The drug loss despite multiple washing was significantly low (p,<,0.001) for the bilayered lacquer owing to the protective vinyl coating. Clinical studies demonstrated the efficacy of bilayered lacquer to achieve better drug load in the nail plate (1.27,±,0.184,µg/mg) compared to monolayer (0.67,±,0.18,µg/mg) and control (0.21,±,0.04,µg/mg) lacquers. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4267,4276, 2010 [source] Poly[[[aqua(2,2,-bipyridine-,2N,N,)manganese(II)]-,-croconato-,4O,O,:O,,,O,,,] monohydrate]: a one-dimensional coordination polymer connected by hydrophilic,hydrophilic and lipophilic,lipophilic interactions at 135,KACTA CRYSTALLOGRAPHICA SECTION C, Issue 4 2010Hong-Feng Chen In the title one-dimensional coordination polymer, {[Mn(C5O5)(C10H8N2)(H2O)]·H2O}n, each MnII ion is seven-coordinated by four O atoms from two croconate ligands, two N atoms from a 2,2,-bipyridine (2,2,-bipy) ligand and one O atom from an aqua ligand. The croconate ligand bridges the MnII ions in a bis-bidentate chelation mode, forming an extended [Mn(C5O5)]n chain running parallel to the [001] direction, with the lipophilic 2,2,-bipy ligands lying along one side and the hydrophilic water molecules along the opposite side. Coordinated water and solvent water molecules are arranged in the hydrophilic layer, which is characterized by O,H...O hydrogen bonds between croconate ligands. Meanwhile, 2,2,-bipy ligands from adjacent chains partially overlap and exhibit ,,, interactions to form a lipophilic layer. The hydrophilic and lipophilic layers are arranged alternately to build a layer structure. [source] Effect of lipid bilayer alteration on transdermal delivery of a high-molecular-weight and lipophilic drug: Studies with paclitaxelJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2004Ramesh Panchagnula Abstract Skin forms an excellent barrier against drug permeation, due to the rigid lamellar structure of the stratum corneum (SC) lipids. Poor permeability of drugs can be enhanced through alteration in partition and diffusion coefficients, or concentration gradient of drug with an appropriate choice of solvent system, along with penetration enhancers. The aim of the current investigation was to assess applicability of lipid bilayer alteration by fatty acids and terpenes toward the permeation enhancement of a high-molecular-weight, lipophilic drug, paclitaxel (PCL) through rat skin. From among the fatty acids studied using ethanol/isopropyl myristate (1:1) vehicle, no significant enhancement in flux of PCL was observed (p,>,0.05). In the case of cis mono and polyunsaturated fatty acids lag time was found to be similar to control (p,>,0.05). This suggests that the permeation of a high-molecular-weight, lipophilic drug may not be enhanced by the alteration of the lipid bilayer, or the main barrier to permeation could lie in lower hydrophilic layers of skin. A significant increase in lag time was observed with trans unsaturated fatty acids unlike the cis isomers, and this was explained on the basis of conformation and preferential partitioning of fatty acids into skin. From among the terpenes, flux of PCL with cineole was significantly different from other studied terpenes and controls, and after treatment with menthol and menthone permeability was found to be reduced. Menthol and menthone cause loosening of the SC lipid bilayer due to breaking of hydrogen bonding between ceramides, resulting in penetration of water into the lipids of the SC lipid bilayer that leads to creation of new aqueous channels and is responsible for increased hydrophilicity of SC. This increased hydrophilicity of the SC bilayer might have resulted in unfavorable conditions for ethanol/isopropyl myristate (1:1) along with PCL to penetrate into skin, therefore permeability was reduced. The findings of this study suggest that the permeation of a high-molecular-weight and lipophilic drug cannot be enhanced through bilayer alteration by penetration enhancers, and alteration in partitioning of drug into skin could be a feasible mode to enhance the permeation of drug. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2177,2183, 2004 [source] Lamotrigine, an antiepileptic drug, and its chloride and nitrate saltsACTA CRYSTALLOGRAPHICA SECTION C, Issue 9 2009Balasubramanian Sridhar In lamotrigine [systematic name: 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine], C9H7Cl2N5, (I), the asymmetric unit contains one lamotrigine base molecule. In lamotriginium chloride [systematic name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium chloride], C9H8Cl2N5+·Cl,, (II), the asymmetric unit contains one lamotriginium cation and one chloride anion, while in lamotriginium nitrate, C9H8Cl2N5+·NO3,, (III), the asymmetric unit contains two crystallographically independent lamotriginium cations and two nitrate anions. In all three structures, N,H...N hydrogen bonds form an R22(8) dimer. In (I) and (II), hydrophilic layers are sandwiched between hydrophobic layers in the crystal packing. In all three structures, hydrogen bonds lead to the formation of a supramolecular hydrogen-bonded network. The significance of this study lies in its illustration of the differences between the supramolecular aggregation in the lamotrigine base and in its chloride and nitrate salts. [source] | ||||||||||