Thermosensitive Gel Nasal Spray With Stem Cell Exosomes, Mupirocin, and DNase I for Chronic Sinusitis

Overview

This study tests a new nasal spray for adults (18-65 years) with chronic rhinosinusitis (CRS) without nasal polyps. The spray contains a temperature-sensitive gel (thermosensitive gel) that turns into a soft gel inside the nose to slowly release three active ingredients: human umbilical cord mesenchymal stem cell exosomes (hUC-MSC-Exo) to help heal the nasal lining, mupirocin (an antibiotic that kills Staphylococcus aureus bacteria), and DNase I (an enzyme that breaks down thick mucus). The study aims to check the safety of this triple combination and see if it can reduce infection, clear mucus, and improve symptoms. Participants will be randomly assigned to one of three groups: triple spray, a dual spray (without exosomes), or a placebo (gel only). The treatment is used twice daily for 4 weeks, with follow-up visits up to day 90. The study is single-centre, double-blind, and placebo-controlled. Outcome measures include safety (adverse events graded by Common Terminology Criteria for Adverse Events version 5.0, CTCAE v5.0), bacterial clearance rate, changes in nasal endoscopy score (Lund-Kennedy), quality of life (Sino-Nasal Outcome Test-22, SNOT-22), and nasal symptom visual analog scale (VAS).

This is an exploratory, single-centre, randomised, double-blind, placebo-controlled clinical study. A total of 108 participants (allowing for 20% dropout) will be enrolled and allocated in a 1:1:1 ratio to three parallel groups: * Group A (triple combination): thermosensitive gel + human umbilical cord mesenchymal stem cell exosomes (hUC-MSC-Exo, 1×10\^10 particles/mL) + mupirocin (2%) + DNase I (0.1%). * Group B (dual control): gel + mupirocin (2%) + DNase I (0.1%). * Group C (placebo): blank gel matrix only. The gel matrix consists of Poloxamer 407 (18%) and chitosan hydrochloride (0.5%) in sterile phosphate-buffered saline (PBS, pH 6.4-6.8). At room temperature it is a liquid; upon contact with the nasal mucosa (33-35°C) it forms a semi-solid gel within 30 seconds, enabling sustained release. Participants aged 18-65 years with diagnosed chronic rhinosinusitis (CRS) without polyps (duration \>12 weeks), Lund-Kennedy secretion score ≥1, positive nasal culture for Staphylococcus aureus, and Sino-Nasal Outcome Test-22 (SNOT-22) score ≥30 are eligible. Key exclusion criteria include sinus surgery within 6 months, nasal polyps, Pseudomonas aeruginosa as the primary pathogen, use of systemic antibiotics/immunosuppressants within 4 weeks, and pregnancy. The treatment period is 28 days, with twice-daily dosing (morning and evening). Each dose: 2 sprays per nostril (50 microlitres per spray). Single-spray dose: exosomes 2×10\^9 particles, mupirocin 4 mg, DNase I 0.2 mg. Daily total doses are doubled. Study visits include screening (day -7 to 0), treatment (days 1, 7, 14, 21), end-of-treatment (day 29±2), short-term follow-up (day 42±3), and long-term follow-up (day 90±7). Primary outcome: safety assessed by adverse events (Common Terminology Criteria for Adverse Events version 5.0, CTCAE v5.0). Secondary outcomes: bacterial clearance rate of Staphylococcus aureus, change in neutrophil extracellular traps (NETs) levels measured by MPO-DNA enzyme-linked immunosorbent assay (ELISA), mucus viscosity (rheometer), endoscopic Lund-Kennedy score (0-20, higher=worse), SNOT-22 score (0-110, higher=worse), visual analog scale (VAS) symptom diary (0-10, higher=worse), and number of acute exacerbations. Exploratory outcomes include biofilm disruption (electron microscopy), inflammatory cytokines (interleukin-8, IL-8; interleukin-17, IL-17; tumour necrosis factor-alpha, TNF-α; interleukin-10, IL-10), tight junction proteins (zonula occludens-1, ZO-1; occludin), 16S ribosomal RNA (rRNA) microbiome diversity, and mupirocin susceptibility testing. The trial will be conducted at The First Affiliated Hospital of Henan Medical University (Zhongyuan Regenerative Medicine Laboratory). It has received ethical approval from the Ethics Committee of The First Affiliated Hospital of Henan Medical University (approval number: 2026-30). The study will adhere to Good Clinical Practice (GCP), the Declaration of Helsinki, and local regulations. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publications.