The impact of the manufacturing process on silk nanoparticle characteristics: A Critical Analysis

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Silk is a long-established biomaterial, but recently there has been growing interest in the use of nanoparticles for targeted drug delivery with much of the manufacturing and evidence centred around silk-based particles. In view of the existing uncertainty regarding how different manufacturing processes can affect the properties of silk nanoparticles, this thesis sought to summarise the findings of the most recent primary literature. A search for recent literature was undertaken in July 2021 using the databases of MEDLINE, Scopus and Web of Science. The article search restrictions were set to publication since the year 2010, English language and peer review. Evidence was appraised using the principles of the Critical Appraisal Skills Program (CASP) and analysed using narrative synthesis due to the significant inter-study heterogeneity that precluded meta-analysis. A total of 11 evidence sources were found to be eligible for review, of which all 11 comprised in vitro studies. Narrative synthesis revealed that bottom-up techniques using varied manufacturing methods generated nanoparticles of varying size (10-300 nm) within an accepted nanometre range and with adequate drug delivery profiles based on loading capacities (1.8-11.4%), encapsulation efficiencies (40-96% w/w) and release and uptake assays within in vitro models. The aim of this project was to systematically explore and critically evaluate manufacturing process used to generate silk nanoparticles. Overall, this thesis highlights the potential value of silk nanoparticles in drug delivery for a range of drug compounds and for a broad range of diseases and conditions, although ongoing research is critical to advancing the evidence to allow human trials and in turn, approval by drug authorities.