Biocompatibility and sub-chronic toxicity studies of phlorotannin/polycaprolactone coated trachea tube for advancing medical device applications

Abstract

The phlorotannin-polycaprolactone-coated endotracheal tube (PP tube) has been developed with the aim of preventing tracheal stenosis that can result from endotracheal intubation, a factor that can lead to a serious airway obstruction. Its preventive efficacy has been assessed through both in vitro and in vivo investigations. However, there is a lack of studies concerning its biocompatibility and sub-chronic toxicity in animal models, a crucial factor to ensure the safety of its usage as a functional endotracheal tube. Thus, this study aimed to evaluate the biocompatibility and sub-chronic (13 weeks) toxicity of the PP tube through L929 cell line and diverse in vivo models. The cytotoxicity testing was performed using the extracts of PP tube on L929 cells for 72 h. Furthermore, other tests conducted on animal models, including ICR mice (acute systemic toxicity), New Zealand white rabbit (intradermal reactivity and pyrogen tests), guinea pig (maximization sensitization), and Sprague Dawley rats (sub-chronic toxicity). In both biocompatibility and sub-chronic toxicity analyses, no significant adverse effects are observed in the groups exposed to the PP tube, when compared to control group. Altogether, the findings suggested that the PP tube exhibits relative non-toxic and safety, supporting its suitability for clinical usage. However, extended periods of intubation may produce mild irritant responses, highlighting the clinical caution of limiting intubation duration to less than 13 weeks.

Keywords: Biocompatibility; Endotracheal tube; Medical device; Phlorotannin; Sub-chronic toxicity.

Figure 1

In vitro cytotoxicity of extracts of PE tube, PF, and HDPF for 48 h on L929 mouse fibroblast. N.S. Non-significant.

Figure 2

Effect on body weight change of injection of extracts from PP tube in (a) saline and (b) CSO in female mouse for a period of 3 days to evaluate acute systemic toxicity. (c) Temperature changes in rabbits following injection (10 mL/kg) of extract from PP tube in saline to evaluate pyrogenicity effect. N.S. Non-significant.

Figure 3

Effect on body weight of (a) female guinea pig after intracutaneous injection of extract from PP tube in saline and CSO and DNCB (in ethanol, negative control) in female mouse for a period of 48 h to evaluate maximization sensitization and rats after implantation on gluteal muscle of PE (N.C.) and PP tubes in (b) male and (c) female rats for a period of 13 weeks (n = 10, respective). (b). N.S. Non-significant.

Figure 4

Effect on (a,b) food intake and (c,d) water consumption after implantation on gluteal muscle of the PE (negative control) and PP tubes in (a,c) male and (b,d) female rats for a period of 13 weeks of the sub-chronic toxicity study (n = 10, respective). ^*p < 0.05 indicates significant difference compared to negative control group. N.S. Non-significant.