Extemporaneously preparative biodegradable injectable polymer systems exhibiting temperature-responsive irreversible...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Biodegradable injectable polymer (IP) systems are crucial for clinical applications, with rapid preparation and prolonged gelation time being key development targets.
• Previous work established temperature-responsive covalent gelation systems using a bio-orthogonal thiol-ene reaction and a 'freeze-dry with PEG/dispersion' method for rapid IP formulation.
• The amphiphilic biodegradable tri-block copolymer (tri-PCG) with terminal acryloyl groups (tri-PCG-Acryl) was identified as a key component in these systems.

Purpose of the Study:

• To apply the 'freeze-dry with PEG/dispersion' method to a temperature-triggered covalent gelation system for injectable polymers.
• To evaluate the preparation speed, gelation properties, and in vivo performance of the newly developed instant formulation.
• To assess the potential clinical convenience of this rapid preparation method for IP systems.

Main Methods:

• Development of an instant formulation (D-sample) using the 'freeze-dry with PEG/dispersion' method, involving mixing micelle dispersions of tri-PCG-Acryl and tri-PCG/DPMP with PEG.
• Preparation of the D-sample formulation within 30 seconds from dried components at room temperature.
• Comparison of the D-sample's gelation behavior and duration with a standard formulation (S-sample) prepared by conventional heating dissolution.
• Evaluation of biocompatibility and gel state duration after subcutaneous implantation.

Main Results:

• The instant formulation (D-sample) was prepared rapidly (30 seconds) using the 'freeze-dry with PEG/dispersion' method.
• The D-sample exhibited irreversible gelation and a long gel state duration, comparable to the conventionally prepared S-sample.
• Notably, the D-sample maintained a sol state for a significantly longer period (24 hours) at room temperature compared to the S-sample (3 hours).
• Subcutaneous implantation demonstrated good biocompatibility and sustained gel state duration for the IP system.

Conclusions:

• The 'freeze-dry with PEG/dispersion' method enables quick extemporaneous preparation of temperature-triggered covalent gelation systems for injectable polymers.
• The developed instant formulation offers enhanced stability in the sol state before injection and a prolonged gel state in vivo.
• These characteristics significantly improve the convenience and potential clinical applicability of biodegradable injectable polymer systems.