Synthesis of low molecular weight poly(lactide-co-caprolactone) as tissue adhesives and tetracycline drug release

Abstract

Lactide-based polymers are widely used in various biomedical applications including surgical fixation devices and controlled drug delivery system. An ideal tissue adhesive and drug release system must adhere to the tissue substrates and sustain drug throughout the wound healing process. Additionally, it should biodegrade without side effect or systematic toxicity. Ring-opening copolymerization of L-lactide and [Epsilon] -caprolactone using alcohols with different numbers of hydroxyl groups as co-initiator was prepared in the presence of Sn(Oct)[subscript 2]. Two series of low molecular weight copolymers with similar arm length and molecular weight were synthesized and characterized by [superscript 1]H NMR, GPC and DSC. Among all of the copolymers synthesized, D-sorbitol was not suitable to be used as co-initiator for copolymerization as tissue adhesive and drug release system and T[subscript g] of copolymers with similar arm length are controlled between 20-25°C. In film preparation, copolymer was incorporated to chitosan at suitable ratio (70/30, copolymer/chitosan, w/w). Blend film of copolymer using pentaerythritol as co-initiator and chitosan (CO-PTOL/CH) gave the highest adhesive property that measured by T-peel test. The tetracycline hydrochloride (TCH) release from blend film was investigated in phosphate buffer saline at 37°C. The CO-PTOL/CH (5% TCH) can prolong the release of TCH within 7 days compared with chitosan film which is consistent with swelling behavior. Furthermore, this film can release drug with high %drug release (84.08%). Therefore, it is the most suitable TCH drug release system.