Sporopollenin exines as a novel drug delivery system
Blackwell, Lisa Jane
Thesis or dissertation
- © 2007 Lisa Jane Blackwell. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Microcapsules are fast becoming the most successful delivery systems for the oral delivery of drugs and food additives. Since many drugs are proteins and are destroyed in acidic conditions, microcapsules offer protection against the harsh environment of the gastrointestinal (GI) tract. Although the use of microcapsules achieves controlled release of the inner material, many synthetically designed microcapsules lack consistency in their size and morphology.
The outer coat (exine) of plant pollen grains and spores is composed of the material sporopollenin. Sporopollenin exines (25µm diameter) were extracted from Lycopodium clavatum and were investigated as a novel drug delivery system that was inexpensive, non-toxic, from a renewable source, and exhibited a large internal cavity for loading of hydrophobic and hydrophilic substances. They showed many advantages over conventional microcapsules, including their constant chemical structure and size within a species, and their ability to offer UV and air-oxidation protection.
Previous studies have shown that particles such as pollen, spores and starch migrate into the bloodstream following ingestion by a process termed 'Persorption'. Such findings intrigued many researchers but the phenomenon has not been unanimously accepted. This research is a body of evidence giving unequivocal confirmation that spores of Lycopodium clavatum and their emptied exines were absorbed into the bloodstream of man to the same extent following oral ingestion, with a maximum of 10% (± 2%) of the dose recovered just 15-30 minutes after ingestion. These findings resolve the debate between researchers in support of persorption and those against, whom doubted the transport of particles of micron size into the bloodstream, but did not disprove such a phenomenon. An extensive study was undertaken to investigate the effect of factors such as gender, age, quantity and the method of ingestion on the rate and extent of exine absorption into the bloodstream. In a preliminary in vivo experiment the successful delivery of fish oil into the bloodstream via sporopollenin exines was illustrated.
A major breakthrough has formed the foundations of this research. Although sporopollenin exhibits incredible stability to organIc and inorganic solvents, in contrast, this research has shown that exines degrade very rapidly in blood plasma both in vitro and in vivo. In vitro experiments were conducted in an attempt to characterise the specific mechanism responsible for exine degradation. Progression of work has provided much evidence that the conversion of plasminogen to the enzyme plasmin is either partially or wholly responsible for the characteristic degradation of sporopollenin in the blood.
Further investigations showed that it was possible to load a sufficient quantity of substances into sporopollenin exines, such as human growth hormone (hGH) , Enfurvitide (an antiretroviral agent used in the treatment of AIDS) and Cyclosporine (an antifungal agent). Their successful release from exines into different media in vitro and in vivo (carried out in Beagle dogs) was shown.
These in vivo experiments highlighted the need for extra protection of the drug from the GI tract and additional coatings were applied to sporopollenin exines, including a soluble form of sporopollenin. Exines with coatings were assessed to ensure they were still able to degrade in blood and release the encapsulated substance.Current results are highly indicative that sporopollenin could become a practicable oral delivery system for molecules that are otherwise problematic to administer, such as protein drugs that degrade rapidly in acidic conditions.
- Department of Chemistry, The University of Hull
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