Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265759
Title: The interaction of a model steroid with phospholipid structures
Author: Parmar, Rina
ISNI:       0000 0001 3472 5681
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1997
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Abstract:
This thesis describes investigations into the entrapment of beclomethasone dipropionate (BDP) into phospholipid structures, in order to understand the behaviour of this drug within monolayers and bilayers, and to help optimise future steroid entrapment in liposomes for drug delivery. BDP monohydrate forms a solvate when recrystallised from chloroform, and its size and shape may affect liposomal entrapment. BDP crystals are present in liposomes at concentrations of 1.5-2 mole % steroid, and form on the hydration of dry phospholipid films. Unentrapped material was efficiently removed from liposomal suspensions by centrifugation in deuterated water, with crystals forming a pellet. An HPLC assay for the determination of BDP was developed, and the maximum entrapment of this steroid in dipalmitoylphosphatidylcholine (DPPC) liposomes was found to be 2.5 mole % BDP. Fluorescence studies of monolayers indicated that BDP increases the surface pressure at which DPPC solid domains form. BDP is expelled out from compressed DPPC, distearoylphosphatidylcholine, dipalmitoylphosphatidic acid and dipalmitoyl- phosphatidylglycerol monolayers, into the hydrophobic super-phase region. BDP increased the surface pressures of condensed dilaurylphosphatidylcholine monolayers, as the hydrophobic regions of this phospholipid are near to the aqueous sub-phase surface. DSC investigations into the effects of BDP on phospholipid bilayers found that the optimal interaction between steroid and phospholipid molecules, monitored by transition peak width values, occurs with C18 phospholipid chains (distearoyl) and large head-groups (phosphatidylglycerol). BDP molecules seem to be located at the terminal chain regions, probably due to their size and shape. Domain formation by BDP affects thermal profiles only when domains increase and modify the mid-chain region. The relative instability of BDP molecules in the disordered region of bilayers may explain why BDP, although hydrophobic, does not incorporate into liposomes to any great extent. These results have important practical implications for achieving higher BDP entrapment efficiencies in liposomes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.265759  DOI: Not available
Keywords: Drug delivery; Steroid entrapment; Liposomes
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