PLGA Conformational Behaviour Dependence of the Network Characterized by Rheological Study

The aim of the study was to investigate the organization and evolution of poly (lacticde-co-glycolide acid) (PLGA) network varied with the PLGA conformational behavior in different solvent systems. INTRODUCTION PLGA-based controlled release systems have been studied widely with the aim of sustained delivery of proteins. To date, many attempts have been made to understand the release mechanisms of PLGA-based controlled release systems in order to customize the release towards to the specific purpose. Despite this, the mechanisms of drug release from PLGAbased controlled release systems are still not fully understood. Especially, so-called ‘initial burst’ phenomenon poses a serious toxicity threat and is a major hurdle for the development of PLGA-based controlled release products. Furthermore, PLGA-based controlled release systems tend to have a very slow release period after the initial burst period. This period usually lasts for days to weeks and is often referred to as the lag time period. During this lag time, the patient may not be effectively treated due to the lack of sufficient drug release. Hence, it is necessary to understand the mechanisms in the initial burst period and lag time period. At present, it is only simply known that the initial burst release is related to the rapid release of drug from the surface of PLGA-based controlled release systems, and the lag time period starts from the depletion of drug at the surface and lasts until extensive degradation of the polymer. However, the delicate understanding of the mechanism of the initial burst and lag time in the molecular level is still scarce. In particular, the role of PLGA conformational structure in drug release process has not been fully explored. It is known that random coils of polymer molecules are very loose entities and occupy a large volume per mass. With increasing polymer concentration, the free space between the coils is decreasing, until the concentration is so high that they come into close contact and coil overlap occurs. At the concentration above the overlap concentration (c*), overlapping of molecules becomes so prominent that segments of different chains begin to entangle. Molecules sections between two entanglements behave as quasi-independent blobs. The diameter of a blob (the distance between two adjacent entanglements) is the mesh size of the network generated by entanglements, and the blobs in good solvents are more compressed. Hence, it is rational to speculate that the networks would be influenced by the PLGA conformational behaviour in the solutions, and thus, the different drug release kinetics would also be expected. In this study, we investigated the PLGA Conformational Behaviour Dependence of the Network Characterized by