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Document Type:Latin Dissertation
Language of Document:English
Record Number:55019
Doc. No:TL24973
Call number:‭3334419‬
Main Entry:Uwais Muhammad Syed
Title & Author:Cochleates bridged by drug moleculesUwais Muhammad Syed
College:Long Island University, The Brooklyn Center
Date:2008
Degree:Ph.D.
student score:2008
Page No:87
Abstract:The membrane fusion capacity of cochleates is more important for the delivery of hydrophilic drugs. However, cochleates and nanocochleates have not demonstrated an effective microencapsulation of hydrophilic drugs. Since cochleates are formed by ionic interaction between negatively charged liposomes and bivalent cations, microencapsulation of cationic drugs using themselves as the bridging agents of cochleation can be rationalized. In order to test this hypothesis, two water soluble and multivalent cationic molecules, i.e., tobramycin and polylysine (oligo-peptide) were used to form cochleates with negatively charged liposomes. A new type of cochleate, able to microencapsulate water-soluble cationic drugs or peptides into its inter-lipid bi-layer space, was formed through interaction between negatively charged lipids and the drugs or peptides acting as the inter-bi-layer bridges instead of multi-cationic metal ions. This new type of cochleate opened up to form large liposomes when treated with EDTA, suggesting that cationic organic molecules can be extracted from these cochleates in a way similar to multivalent metal ions from metal ion-bridged cochleates. Cochleates can be produced in sub-micron size using a method known as "hydrogel-isolated-cochleation" or simply by increasing the ratio of multivalent cationic peptides over negatively charged liposomes. When nanometer sized cochleates and liposomes containing the same fluorescent-labeled lipid component were incubated with human fibroblasts cells under identical conditions, cells exposed to cochleates showed bright fluorescent cell surfaces, whereas those incubated with liposomes did not. This result suggests that cochleates' edges made them fuse with the cell surfaces as compared to edge free liposomes. This mechanism of cochleates' fusion with cell membrane was supported by a bactericidal activity assay using tobramycin cochleates which act by inhibiting intracellular ribosomes. Tobramycin bridged cochleates in nanometer size showed improved antibacterial activity than the drug's solution.
Subject:Health and environmental sciences; Pure sciences; Cationic drugs; Cochleates; Hydrophilic drugs; Microencapsulation; Nanocochleates; Nanoparticles; Pharmacology; Pharmacy sciences; 0419:Pharmacology; 0491:Pharmacy sciences
Added Entry:F. J. Plakogiannis, Tuo
Added Entry:Long Island University, The Brooklyn Center