Influence of environmental tonicity changes on lipophilic drug release from liposomes
AuthorNikolaisen, Trygg Einar
Introduction: Liposomes as drug delivery systems has been widely studied as a way to solubilize poorly soluble drugs, reduce side effects of chemotherapeutics and increase circulation time in vivo. Since the first descriptions of liposomes over 60 years ago, they have shown tendencies to shrink and swell when the external environment of the liposomes is altered. This phenomenon has been studied in recent years and it is now known that liposomes’ shape is affected by osmotic pressure. Aim: The aim of this thesis was to clarify if changing the tonicity (i.e. concentration of solutes) outside of large unilamellar vesicles (LUVs) would affect the release of lipophilic drugs from them. Methods: LUVs were made by evaporating the solvent from a solution consisting of lipid, drug and solvents in phosphate buffered saline (PBS), and subsequently extruded to the desired sizes. The LUVs were characterized in terms of average diameter, size distribution, surface charge and percentage of drug entrapped inside the LUVs. To understand how tonicity affects the size of vesicles, the external environment of the LUVs was changed, and the size distributions of the LUVs were measured over time. The permeation properties of hydrocortisone and methylprednisolone were studied using Franz cells setup at different osmotic pressures using cellulose hydrate membranes or Permeapad® biomimetic barrier for both drug suspensions and drug-liposomal dispersions. Results and conclusion: We demonstrated that the LUVs shrank and swelled when the tonicity of the external environment was altered. We also demonstrated that the permeability of drugs (incorporated into LUVs) through cellulose hydrate membranes were highly affected by changes in tonicity. A significantly lower permeability for both hydrocortisone and methylprednisolone from the liposomal formulation in hypertonic external environment was measured, whereas no significant changes were found for the hypotonic external environment. The permeability studies on hydrocortisone incorporated LUVs employing the, Permeapad® showed a significantly higher permeability when changing the tonicity to hypotonic environment.
Klarer ikke gjennomføre sak: Failed to perform step 1 in Navigate Stage 'Activate Adobe Reader + Click Center' on page 'Read PDF' - Could not identify process owning the current foreground window
PublisherUiT Norges arktiske universitet
UiT The Arctic University of Norway
The following license file are associated with this item:
Showing items related by title, author, creator and subject.
Molecular modeling of 3D structure of the oxytocin receptor. Discovery of novel oxytocin receptor agonists via molecular docking studies. Antobreh, Gloria Tiwaa (Master thesis; Mastergradsoppgave, 2015-05-15)Oxytocin has been shown to be implicated in psychiatric diseases such as depression, anxiety disorders, autism post-traumatic stress disorder, and schizophrenia. As a result, oxytocin can be used as a potential treatment for these brain disorders. However, oxytocin is a large peptide, and is therefore unable to cross the blood brain barrier. Thus, the development of new small non-peptide drugs would ...
Abel zur Wiesch, Pia; Clarelli, Fabrizio; Cohen, Ted (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-01-06)Identifying optimal dosing of antibiotics has proven challenging—some antibiotics are most effective when they are administered periodically at high doses, while others work best when minimizing concentration fluctuations. Mechanistic explanations for why antibiotics differ in their optimal dosing are lacking, limiting our ability to predict optimal therapy and leading to long and costly experiments. ...
Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma : VEGF-A Impact Is Strongly Associated with Ang-2 Andersen, Sigve; Dønnem, Tom; Al-Shibli, Khalid Ibrahim; Al-Saad, Samer; Stenvold, Helge; Busund, Lill-Tove; Bremnes, Roy M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor Tie-2, as well as their relation to the prognostic expression of VEGF-A. 335 unselected stage I-IIIA NSCLC-patients were included and tissue samples of respective tumor cells and ...