Synthesis of biodegradable microparticles for controlled active ingredient release

Abstract

This thesis investigates the degradation and release of a fluorescent dye from biodegradable microparticles. Particular attention is given to determining the effect of polymeric properties on the subsequent microparticle degradation and release rate. Chapter 1 reviews the current polymerisation techniques for the synthesis of polyesters and introduces the synthetic procedures and degradability currently attainable for biodegradable microparticles. The concept of ‘smart’ release technology is introduced and the potential for using biodegradable ‘smart’ particles for enhanced agricultural formulations is explored. In Chapter 2, the ring-opening polymerisation (ROP) of a variety of polyesters is demonstrated, including an investigative study on the ROP of poly(3-hydroxybutyrate) (PHB) using magnesium 2,6-di-tert-butyl-4-methylphenoxide (Mg(BHT)2(THF)2). The polyesters are used to prepare microparticles via a single oil-in-water solvent evaporation technique, a range of formulation parameters are studied to enable optimisation of the subsequent particle size and stability. Chapter 3 investigates the encapsulation of a model fluorescent dye into poly(L-lactide) (PLLA) microparticles and the subsequent PLLA particle degradation and dye release under simulated environmental conditions is reported. Chapter 4 describes the degradation and release of 3-bromo-4-(butylamino)-2,5-dihydro-1H- pyrrole-2,5-dione (ABM) from a range of polyester microparticles, investigating the effect of polymer properties (e.g., molecular weight, crystallinity, etc.) on the particle degradation and release rate. In Chapter 5, the incorporation of a stimulus responsive polymer using optimised particle synthesis and degradation conditions (detailed in Chapter 2 and 3) is investigated. The successful tuneable microparticle degradation and release is described by incorporation of a light-responsive poly(nitrobenzyl malic acid) (PNO2BnMA) into homopolymer blends of PLLA microparticles. Chapter 6 explores the synthesis of degradable poly(vinyl acetate) (PVAc) microparticles by the incorporation of 2-methylene-1,3-dioxepane (MDO) degradable ester linkages into the polymer backbone via free radical ring-opening polymerisation (rROP) and post- polymerisation microparticle synthesis (using the optimised solvent evaporation technique detailed in Chapter 2). The successful encapsulation of ABM into P(MDO-co-VAc) microparticles is reported and compared to encapsulation into PVAc microparticles. In Chapter 7, the synthesis of poly(ω-pentadecalactone) (PPDL) microparticles using the optimised single oil-in-water emulsion technique (Chapter 2) is reported. Investigation into the synthesis and degradation of films prepared from random copolymers of PPDL and poly(ɛ- caprolactone) (PCL) is described. An attempt at polymerisation-induced self-assembly (PISA) using block copolymers of PPDL and poly(ɛ-decalactone) (PeDL) is demonstrated. In chapter 8, a general summary of Chapters 2-7 is presented and key findings and conclusions highlighted. Chapter 9 provides the experimental methods used throughout this thesis and Chapter 10 provides supporting degradation studies for Chapter 3 and 4