Abstract
Poly(glycerol adipate) (PGA) is a biodegradable, biocompatible, polymer with a great deal of potential in the field of drug delivery. Active drug molecules can be conjugated to the polymer backbone or encapsulated in self-assembled nanoparticles for targeted and systemic delivery. Here, a range of techniques have been used to characterise the enzymatic degradation of PGA extensively for the first time and to provide an indication of the way the polymer will behave and release drug payloads in vivo. Dynamic Light Scattering was used to monitor change in nanoparticle size, indicative of degradation. The release of a fluorescent dye, coupled to PGA, upon incubation with enzymes was measured over a 96 h period as a model of drug release from polymer drug conjugates. The changes to the chemical structure and molecular weight of PGA following enzyme exposure were characterised using FTIR, NMR and GPC. These techniques provided evidence of the biodegradability of PGA, its susceptibility to degradation by a range of enzymes commonly found in the human body and the polymer’s potential as a drug delivery platform.
Highlights
Poly(glycerol adipate) (PGA) is synthesised by enzymatic polymerisation from glycerol and either divinyl adipate, dimethyl adipate or adipic acid, using Novozym 435 lipase as the catalyst, allowing a high degree of control over the final product [1,2,3,4]
Dynamic Light Scattering (DLS) showed that the size of PGA nanoparticles increases after the addition of a range of enzymes, with the extent of this change differing depending on the enzyme and polymer modifications
Nuclear Magnetic Resonance (NMR), FourierTransform Infra-Red (FTIR) and Gel Permeation Chromatography (GPC) were used to confirm the breakdown of the polymer in the presence of lipase, elastase and esterase; complete breakdown was seen with lipase whereas partial breakdown could be seen with the other two enzymes
Summary
Poly(glycerol adipate) (PGA) is synthesised by enzymatic polymerisation from glycerol and either divinyl adipate, dimethyl adipate or adipic acid, using Novozym 435 lipase as the catalyst, allowing a high degree of control over the final product [1,2,3,4]. The presence of the pendant eOH group in the polymer backbone allows for the conjugation of molecules with a variety of functional groups through simple coupling reactions, influencing the physicochemical properties of PGA and its ability to encapsulate a variety of drugs [6,8,9,10]. These changes to the polymer as a result of the modifications suggest the enzymatic degradation will be affected due to the enhanced stability, altered hydrophobicity and increased steric hindrance, leading to a potential for tunable breakdown and release in vivo. The low toxicity of PGA coupled with the ease with which it can be synthesised, functionalised with drug molecules and formulated into nanoparticles means it shows great potential as a polymeric platform for both targeted and systemic drug delivery
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