Development of polycaprolactone microparticles as a protein delivery system for the treatment of tendon disorders.

Walden, Grace (2019) Development of polycaprolactone microparticles as a protein delivery system for the treatment of tendon disorders. Doctoral thesis, University of East Anglia.

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This thesis describes the development of a microparticle system, containing bioactive molecules for use in the regeneration of tendon tissue. An introduction is given into the cause of tendon injury and subsequent changes to the tissue post healing, as well as the shortcomings in treatments. The current state of the art in the field is given, including the use of cells and proteins for tissue engineering, polymer candidates for regenerative medicine, click chemistry for protein conjugation, and microparticles as drug delivery systems.

The 3 results and discussion chapters highlight the successful synthesis of a microparticle system template that can conjugate proteins via an azide-alkyne click chemistry dibenzocyclooctyne linking unit. The synthesis of a novel polymer; polycaprolactone azide is described in chapter 2, showing the ability to conjugate to the linking unit in 30 minutes. Chapter 3 describes the subsequent use of the polymer for the formulation of microparticles via membrane emulsion technique. Microparticles from 10-153 μm were produced, with size controlled by altering process parameters such as stir speed and polymer concentration. A live/dead staining assay showed microparticles display no toxicity to tenocytes. The availability of the azide is demonstrated by the conjugation of an alkyne containing fluorescent compound to microparticles. Chapter 4 shows the successful conjugation of 4 proteins; bovine serum albumin, human serum albumin, transforming growth factor βeta 1 and 3 to microparticles. This reaction was efficient, with human serum albumin conjugation occurring in 10 minutes in physiological conditions. Two different linking molecules, with a conserved dibenzocyclooctyne core, were used. Attachment to the microparticles was via azide-alkyne click reaction and to protein via either an N-hydroxysuccinimide ester or thiol-maleimide reaction.

Chapter 5 reviews the translation of academic research to a commercial product, supported by a 3-month studentship with Neotherix Ltd. Chapter 6 is a brief conclusion on the success of the project and future work that could be attempted to progress it further.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Users 11011 not found.
Date Deposited: 17 Oct 2019 13:40
Last Modified: 02 Jan 2020 01:38

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