Tuning drug release in polyester thin films: terminal end-groups determine specific rates of additive-free controlled drug release

Abstract

Modulating the drug release from polyester matrices independently of material properties would be beneficial to those designing biodegradable medical implants, such as drug delivery devices, stents and screws. However, the most common approaches use additives that often drastically alter the desired material properties. Recently, we have developed tools that allow gradient film formulations and high-throughput drug quantitation for the determination of parameter-specific correlations. We propose that modulated drug release can be obtained via additive-free mechanisms in polyesters by simply controlling polymer erosion through acidic terminal functional groups. Our results showed that drug release in poly(lactic-co-glycolic acid) (PLGA) formulations could be tuned to produce large ranges in drug release with relatively small changes in terminal acidic functional groups. For example, PLGA 53/47 thin films could be tuned to have 10–60% drug release at 14 days or 10–90% drug release at 20 days, depending on the PLGA/PLGA blend formulation and concentration of acidic terminal functional groups. A linear R-square correlation of up to 0.9 was observed for the acidic groups and percent drug release. Below a threshold of 1 part per thousand acidic groups, there was no increase in drug release, which has implications for polymer processing and film integrity. Biodegradable, biocompatible polyesters such as polyester poly(lactic-co-glycolic acid) (PLGA) are well suited to drug delivery: species ranging from small molecules to vaccines can be trapped within thin films or small particles of the material, and released on its degradation in the body. Control of the release rate is commonly achieved by incorporating additives to the polyester matrix, for example polyethylene glycol. However, this also affects other characteristics, such as the material's mechanical or swelling properties. To circumvent this issue, Terry Steele, Joachim Loo, Subbu Venkatraman and co-workers from Nanyang Technological University in Singapore have explored how the polyester's molecular weight and terminal functional groups could be used instead. Small variations in the PLGA terminal groups — replacing some of the standard ester group for more soluble carboxylic acid moieties — proved to have a significant effect on the material's degradation, and thus the release of drug molecules from thin films. Modulating the drug release from polyester matrices independently from the material properties would be beneficial to those designing biodegradable medical implants, such as drug delivery devices, stents and screws. We propose that modulated drug release can be obtained via an additive-free mechanism in polyesters by simply controlling polymer erosion through acidic terminal functional groups. The formulations can be tuned to produce large ranges in drug release with relatively small changes in terminal acidic functional groups. For example, poly(lactic-co-glycolic acid) (PLGA) 53/47 thin films could be tuned to have 10–90% drug release at 20 days, depending on the concentration of acidic terminal groups.