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Abdullah, S, 2025. Innovative approaches to peptide-fatty acid conjugates: towards a novel blood brain barrier delivery vector. PhD, Nottingham Trent University.
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Abstract
The human brain is protected by a semipermeable barrier, namely the blood-brain barrier (BBB). The administration of biotherapeutics across the blood-brain barrier remains a formidable challenge due to the barrier's protective nature. The intricate mechanism that drives the progression of neurodegenerative disease, for instance, Alzheimer's disease, presents significant challenges in the search for innovative therapeutic interventions. Despite these challenges, studying neurodegenerative disease remains a crucial area of scientific research, with global scientific organisations striving to develop viable therapies.
This study investigates the embedding of cationic cell-penetrating peptides (CPPs) into liposomes to create innovative vectors that penetrate the BBB and facilitate the delivery of drugs to the brain. The brain-targeted drug delivery system was produced via a microfluidic system. Microwave solid-phase peptide synthesis (MSPPS) was used to produce CPPs and ionic peptides, and characterisated by LC-MS, 1H and 13C NMR. This research also explored the possibility of linking these peptides to three distinct fatty acids (myristic acid, palmitic acid and lauric acid) to facilitate embedding them into the liposomes, while also enhancing their stability and protecting them against enzymatic degradation. The microfluidic lab-on-a-chip was used to prepare the liposomal vector and load them with the carnosine; as a model drug.
In this research, the vectors, with either cationic or ionic peptides conjugated to three distinct fatty acids embedded into liposomes, were applied to an in vitro human BBB model to evaluate performance and toxicity via live cell imaging and MTT assay, respectively. The MTT assay results demonstrated that the vectors embedded with cationic peptides conjugated to fatty acids maintained cell viability above 90% over 72 hours. Live cell imaging demonstrated that endothelial cells treated with these vectors remained viable during the observation period.
The vectors functionalised with cationic CPP-conjugated fatty acids (cationic) were able to deliver the carnosine across the BBB, however, the vectors with ionic peptides, which have a negative charge similar to the cell membrane, did not pass through.
These findings suggest that cationic peptides combined with fatty acids embedded into liposomes hold promise as vectors for the delivery of therapeutics to the brain, particularly for the treatment of neurological diseases such as Alzheimer's disease.
| Item Type: | Thesis |
|---|---|
| Creators: | Abdullah, S. |
| Contributors: | Name Role NTU ID ORCID |
| Date: | February 2025 |
| Rights: | This work is the author's intellectual copyright. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed in the first instance to the owner of the Intellectual Property Rights. |
| Divisions: | Schools > School of Science and Technology |
| Record created by: | Jeremy Silvester |
| Date Added: | 19 Dec 2025 13:46 |
| Last Modified: | 19 Dec 2025 13:46 |
| URI: | https://irep.ntu.ac.uk/id/eprint/54894 |
https://orcid.org/0000-0002-4167-1332Actions (login required)
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