Development and characterization of a sustained release formulation of lidocaine using liposomes exhibiting a transmembrane pH gradient
department or school: Medicine, Faculty of
department or school: Anesthesiology, Pharmacology and Therapeutics, Department of
data provider: DSpace
degree campus: UBCV
creator: Mok, Miranda Jane
issued: 2009-03-09T20:07:26Z
issued: 1997
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Longer acting local anaesthetics which will provide prolonged nerve blockade are required for adequate management of both acute and chronic pain. It has been suggested that liposomes represent a potentially useful vehicle for sustained drug release following local administration. Thus, the aim of this thesis was to develop and characterize liposomal lidocaine by employing a transmembrane pH gradient to efficiently encapsulate lidocaine into large unilamellar vesicles (LUVs). The rate and extent of lidocaine uptake into LUVs exhibiting a pH gradient were determined and compared to drug association with control (no pH gradient) liposomes. While lidocaine was rapidly and efficiently accumulated into liposomes exhibiting a pH gradient, little uptake was seen for control vesicles. The in vitro release kinetics of lidocaine from liposomes were studied and the drug was shown to be slowly released from the carrier with drug efflux being controlled by the applied proton gradient. In addition, it was demonstrated that the rate of lidocaine release from pH gradient-loaded liposomes was only slightly increased in the presence of plasma. Using an in vivo model, the rates of clearance of lidocaine and the lipid carrier were monitored employing radiolabeled markers following intradermal administration. In the guinea pig cutaneous wheal model, the liposomal carrier was found to be cleared slowly from the site of administration, such that greater than 85% of the administered lipid dose remained at 48 hours. Similarly, clearance of liposomally encapsulated lidocaine from the site of administration was relatively slow compared to that of free drug. The guinea pig cutaneous wheal model was again used to investigate the efficacy of the liposomal local anaesthetic formulation. The sustained drug release afforded by liposomes exhibiting a pH gradient resulted in a two-fold increase in the duration of nerve blockade compared to free drug. A similar increase in duration of action was seen w…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/5778
extent: 3432057 bytes
format: application/pdf
note: Development and Characterization of a Sustained Release Formulation of Lidocaine Using Liposomes Exhibiting a Transmembrane pH Gradient by Miranda Jane Mok B.Sc, McGill University, 1993 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTERS OF SCIENCE in THE FACULTY OF GRADUATE STUDIES Department of Pharmacology & Therapeutics We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA January 1997 © Miranda T Mok, 1997 In presenting this thesis in partial fulfilment of. the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. -Department of ftlfl/rVTflCt>{QjLj f ~TheM2peUT]'CS The University of British Columbia Vancouver, Canada Date 07/02, /<? 7 DE-6 (2/88) Abstract Longer acting local anaesthetics which will provide prolonged nerve blockade are required for adequate management of both acute and chronic pain. It has been suggested that liposomes represent a potentially useful vehicle for sustained drug release following local administration. Thus, the aim of this thesis was to develop and characterize liposomal lidocaine by employing a transmembrane pH gradient to efficiently encapsulate lidocaine into large unilamellar vesicles (LUVs). The rate and extent of lidocaine uptake into LUVs exhibiting a pH gradient were determined and compared to drug association with control (no pH gradient) liposomes. While lidocaine was rapidly and efficiently accumulated into liposomes exhibiting a pH gradient, little uptake was seen for control vesicles. The in vitro release kinetics of lidocaine from liposomes were …
has type: Thesis/Dissertation
date issued: 1997-05
is shown at: 10.14288/1.0087628
language: eng
degree discipline: Pharmacology and Therapeutics
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/5778