Colloidal Delivery Systems

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Abstract

In this project we aim to produce a thermally triggered PLGA particulate gel, which is injectable and biocompatible. This will act as a scaffold for soft tissue repair.Three coating polymers were tested; Pluronics (PEG-PPG-PEG), poly(PPGMA-co-PEGMA) and poly(PNIPAm-DMA+). These were first tested as a dilute solution for clouding behaviour and then added to PLGA nanoparticles dispersions and tested rheologically for gel behaviour. These three polymers were chosen for their amphiphilic nature which may allow for surface attachment and decreasing miscibility with temperature.The PLGA copolymer in this work contained 75 % lactic acid and 25 % glycolic acid, and was made into a nanoparticle dispersion by interfacial deposition.The Pluronic L62 showed a promising cloud point temperature (Tclpt) of 37 °C, but did not show gel behaviour with the PLGA dispersions. It conferred thermally triggered aggregation, which may be useful as a drug delivery system. The poly(PPGMA-PEGMA) was synthesised using a free radical polymerisation feed method. These copolymers showed promising Tclpt values (20-37 °C) but only showed increased viscosity when heated at high concentration and when mixed with a PLGA dispersion. The structure-property relationships for these copolymers were analysed. Poly(NIPAM-DMA+) showed gelation at low concentrations without the particles, when the particle dispersion was added the gel maintained its strength up to 300% strain. This is unlike most particulate gels which tend to be brittle. Using cell culture the biocompatibility of these gels was tested. After 72 hours the cells appeared healthy and to be proliferating.

Keyword(s)

Colloid; Gelation; PEGMA; PLGA; PPGMA; Temperature; Thermal

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