Abstracts Category : Other

Controlled drug delivery from self-assembled hydrogels

by Md Musfizur Hassan

Peptide gelators are useful building blocks for creating diverse self- assembled nanostructures, including novel drug delivery systems. The aim of this Thesis is to understand better the key contributing factors in the drug-delivery properties of peptide-based self-assembled hydrogels.Using the archetypical peptide gelators Fmoc (9-fluorenylmethoxycarbonyl)- FF (diphenylalanine); Fmoc-FF 1, as a starting point, the effect of gel concentration, temperature and the size of the (drug) molecule encapsulated on the rate of drug release was investigated. This study was then extended to other gelator including those with different headgroups and di- and tri-peptide analogoues of Fmoc-FF 1 where other hydrophobic amino acids were introduced. The variation in the gel properties such as stiffness correlated well with changes in drug release properties. This study was then extended to longer peptides, containing 4-6 amino acids and inspired by the elastin protein. The resulting elastin-like peptide hydrogels also show good drug release properties which when combined with their elastin-like structure, makes these peptide gelators good candidate for biomedical applications. To assist the release of drugs that are poorly-soluble in water, gelation of Fmoc-FF 1 in various PEG:water mixtures was investigated. This resulted in gels with good mechanical properties. Interestingly, the secondary structures in these gels appears different from gels from 1 in water. The gelation of 1 in this system can be explained by a combination of the macromolecular crowding and hydrophobic effects. Poorly soluble drugs are readily encapsulated and then released in this gel system. Finally, gels based on Fmoc-FF 1 in a mixture of PEG 400 and biological media were used to generate a scaffold for distance- and time-depended drug release in vitro drug release studies targeting the cancer cell line HeLa. A clear relationship between distance from the drug release plug and cell viability was observed in these studies. The work presented in this Thesis has broaden the knowledge drug release from self-assembled peptide gels. The results should therefore benefit further development of these materials for clinical application, be it in the treatment of diseases such as cancer or tissue engineering.Advisors/Committee Members: Thordarson, Pall, Chemistry, Faculty of Science, UNSW.