Synthesis and crystallisation-driven self-assembly of ɛ-substituted poly(ɛ-caprolactones).

Cubillo Alvarez, Ana (2024). Synthesis and crystallisation-driven self-assembly of ɛ-substituted poly(ɛ-caprolactones). University of Birmingham. Ph.D.

Preview

Cubillo2024PhD.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (24MB) | Preview

Abstract

The ability to control the morphology and dimensions of nanostructures is critical to enhance their bioavailability and biological interactions. However, the preparation of non-spherical nanoparticles that can covalently incorporate small molecules in the inner core remains challenging and has not been extensively explored. In this regard, crystallisation-driven self-assembly is a powerful strategy that uses amphiphilic block copolymers containing at least one semi-crystalline block to access a great variety of well-defined 1D and 2D nanostructures. Among these semi-crystalline polymers, poly(ɛ-caprolactone) (PCL) is of high interest owing to its biocompatibility and biodegradability. However, the lack of side group functionality prevents the modification or addition of small molecules, restricting the application of the resultant nanostructures as delivery systems. To overcome this limitation, this thesis focused on the synthesis and self-assembly of substituted PCL-containing amphiphilic block copolymers. The synthesis of semicrystalline substituted PCL was investigated via ring-opening polymerisation following three approaches: i) polymerisation of enantioenriched ɛ-allyl-ɛ-caprolactone, ii) stereoselective polymerisation using a chiral catalyst and iii) copolymerisation of ɛ-caprolactone and ɛ-allyl-ɛ-caprolactone, in which the allyl functional handle enables the attachment of small molecules post-polymerisation. Following this, crystallisation-driven self-assembly of substituted block copolymers with various degrees of functionalisation was explored on different solvent conditions and at different temperatures to give a range of anisotropic structures. Moreover, biological studies demonstrated well-defined 1D and 2D nanoparticles bearing functionalities in the core-forming block exhibited high biocompatibility and considerable internalisation within the cellular cytoplasm, highlighting the great potential of the system for drug delivery applications.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):