Analysis of the sol-to-gel transition behavior of temperature-responsive injectable polymer systems by fluorescence resonance energy transfer

Abstract

Amphiphilic triblock copolymers of poly(ethylene glycol) (PEG) and aliphatic polyesters such as poly(ɛ-caprolactone-co-glycolide) (PCGA) are typical examples of thermogelling polymers. In the gelation mechanism of these polymers, polymer chain transfer between the micelles, and subsequent aggregation of the micelles are important steps. We previously reported IP systems exhibiting temperature-responsive irreversible sol-gel transition that formed covalently cross-linked hydrogels. The IP formulation prepared by the ‘freeze–dry with PEG/dispersion’ method (D-sample) retained its sol state at r.t. longer than a formulation prepared by the usual dissolution method (S-sample). We hypothesized that polymer chain transfer between micelles was suppressed in the D-samples, because the micelle cores were in a solid-like state. In this study, we investigated polymer chain transfer by the fluorescence resonance energy transfer (FRET) method to reveal its role in the sol-to-gel transition. We synthesized a triblock copolymer of PCGA and PEG (tri-PCG) with attached naphthalene or dansyl groups at termini, tri-PCG-nap and tri-PCG-dan, as FRET donors and acceptors, respectively. The FRET behavior of the mixture of tri-PCG-nap/tri-PCG micelles and tri-PCG-dan/tri-PCG micelles was investigated. It was revealed that polymer chain transfer between micelles was strongly accelerated at the gelation temperature, and polymer chain transfer in D-samples was suppressed compared to S-samples. On the gelation of thermogelling polymer solutions, polymer chain transfer between the micelles and subsequent aggregation of the micelles are important steps. In this study, we investigated polymer chain transfer by the fluorescence resonance energy transfer (FRET) method to reveal its role in the sol-to-gel transition. We synthesized amphiphilic triblock copolymer attaching naphthalene or dansyl groups at termini, tri-PCG-nap and tri-PCG-dan. The FRET behavior of the mixture of tri-PCG-nap/tri-PCG micelles and tri-PCG-dan/tri-PCG micelles was investigated.