Development of Drug-Eluting Surgical Sutures for the Wound-Healing Process Using Melt Extrusion Technology

Abstract

Incorporation of an anti-inflammatory drug with polymer materials to produce suture products is important especially when the suture is used for internal organs and/or tissues. In this work, poly(ε-caprolactone) (PCL), polyethylene glycol 400 (PEG400), chitosan and keratin were used as biopolymer matrix to encapsulate 5, 15, 30 wt% diclofenac potassium (DP) to achieve controlled drug release. At first, polymer alone was extruded by hot-melt extrusion technique under various temperatures and at different PCL/PEG400/chitosan-keratin ratios. The products were analysed in terms of FTIR characterization, thermal properties and mechanical properties. According to the characterization analysis of polymer sutures, the optimal polymer formulation (PCL: PEG400: chitosan/keratin= 80:19:1 wt%) (Group 1) was chosen to manufacture sutures with drug DP content at 5, 15, 30 wt%. In addition, PCL/PEG400/chitosan (Group 2) and PCL/PEG400/keratin (Group 3) were also fabricated with drug DP to create sutures, the polymer and drug weight ratios were 95:5, 85:15 and 70:30 wt%. Drug release features were investigated via the drug dissolution test. MTT assay, live/dead assay and scratch assay were also applied to study the biocompatibility of drug embedded sutures. Results showed that sutures can be extruded with a smooth surface and uniform thickness under the temperature of 63 ± 1 °C. It was observed from DSC and TGA studies that completely amorphous and miscible solid dispersions were prepared. FTIR analysis indicated that the presence of hydrogen bonds between the polymers improved material miscibility. Tensile properties of the sutures were clearly affected by PEG400, chitosan and keratin addition. The optimal formulation of tensile strength was obtained when PEG400: chitosan/keratin was 19:1 wt%. The rapid drug release rate was observed at different stages of group 1, 2, 3. For group 1, the release occurred rapidly occurred after 1 h 45 mins, whereas group 2 exhibited fast release between 1 h 45 mins and 3 h 45 mins. Group 3 displayed a sustained release where a fast release occurred from the onset to 3 h 45 mins. However, the final concentration of drug release in group 1 was lower than the other two groups, which can be predicted that a longer drug release time would be in an extended period compared to the other two groups. According to biocompatibility test, group 1 demonstrated very high cell viability at 72 h. Especially sample F3, which contained 30 wt% drug, and the ratio of PCL/PEG/chitosan-keratin was 80/19/1 w/w. It achieved the highest wound healing rate in the scratch assay.