The design and analysis of sugar-based carrier systems for the protection of nucleic acids

Raimi-Abraham, B.T. (2012) The design and analysis of sugar-based carrier systems for the protection of nucleic acids. Doctoral thesis, University of East Anglia.

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Abstract

The overall aim of the work detailed in this thesis was to design and analyse sugar-based (trehalose, raffinose and sucrose) carrier systems for the protection of naked plasmid DNA formulations generated by spray drying.
Trehalose exists in multiple crystalline anhydrous and hydrated forms and is thought to exist in two different amorphous forms. Reported thermal transitions of trehalose dihydrate vary with environmental conditions and particle size. The first area of this thesis focused on investigating the inter-conversion properties of trehalose dihydrate to observe if an in-depth understanding of its physical properties will provide an insight into its bio-protective properties. Within this area, two standardised forms of α,α-trehalose dihydrate were generated and characterised by performing a series of thermal, spectroscopic and X-ray diffraction techniques. This resulted in the identification of an intermediary anhydrous form.
Within the second area of this thesis the use of the fragility parameter m and the strength parameter D as predictors of amorphous stability of generated co-spray dried sucrose-raffinose and sucrose-trehalose samples was investigated. Results showed addition of both raffinose and trehalose improved predicted amorphous stability, with the greatest effect seen at highest additive concentrations.
The third area of the thesis was to evaluate the degree of degradation of plasmid DNA spray dried in the presence of amorphous sugars. Spray-drying can be used to develop biopharmaceutical particles for the pulmonary delivery. However, it runs the risk of loss of
biological activity, sample instability as well as thermal degradation of the biopharmaceutical. Results showed that plasmid DNA degradation was reduced when co-spray dried in the presence of raffinose and to a greater extent with trehalose. Co-spray drying of plasmid DNA in the presence of sucrose, sucrose-raffinose and sucrose-trehalose formulations offered less protection than trehalose and raffinose.
Overall, two key messages are concluded from the work detailed in this thesis. Firstly, the thermal transitions of trehalose dihydrate can be influenced by environmental factors as well as inter-batch variability. This can affect authenticity of polymorphous and amorphous forms identified. Secondly, addition of raffinose and trehalose to amorphous sucrose formulations improved the predicted amorphous stability of the formulations however; these co-spray dried samples offered less protection compared to plasmid DNA co-spray dried in the presence of trehalose and raffinose alone.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Pharmacy
Depositing User:	Users 2259 not found.
Date Deposited:	08 May 2013 11:21
Last Modified:	08 May 2013 11:21
URI:	https://ueaeprints.uea.ac.uk/id/eprint/40463
DOI:

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