Construction of soluble sufentanil microneedles and their analgesic effects in a mouse model of cancer pain

Abstract

Background: Cancer pain severely compromises patients’ quality of life and treatment outcomes, with opioids remaining the mainstay of pharmacological therapy. Soluble microneedle (MN) patches offer a minimally invasive and efficient transdermal drug delivery alternative. This study aims to develop a novel sufentanil-loaded microneedle system (named MN-SF) for the effective and safe management of cancer pain. Methods: Soluble microneedle–hyaluronic acid composite patches were prepared using microforming technology with hyaluronic acid as the matrix material. Microneedles were characterized using optical microscopy and scanning electron microscopy (SEM), and their mechanical strength was evaluated via axial compression testing. The hyaluronic acid concentration was optimized based on microneedle morphology, mechanical hardness, and solubility. A cancer-induced bone pain (CIBP) mouse model was established by intra-femoral injection of 4T1-luc cells into Balb/c mice. Hyperalgesia responses were evaluated in CIBP and sham-operated groups, and CIBP mice received either MN-SF or needle-free patch (NFP) treatment. Analgesic effects were assessed by measuring behavioral responses to thermal and mechanical stimuli. Biocompatibility and safety assessments included histopathological H&E staining, hemolysis tests, serum ALT/AST activity assays, and spontaneous behavior observations. Results: MN-SF patches prepared with 0.1 g mL⁻¹ hyaluronic acid exhibited a uniform 10 × 10 conical array structure with excellent morphological integrity and mechanical strength. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) of sufentanil blood concentrations demonstrated that MN-SF enables effective transdermal penetration and rapid dissolution. In the CIBP model, the MN-SF-administered group demonstrated significantly elevated thermal pain thresholds and mechanical pain thresholds at 30 minutes compared with the control group (P < 0.0001). Hemolysis assays, H&E staining, liver enzyme levels, and spontaneous animal behavior post-administration collectively demonstrated the patch's exceptional biocompatibility. Conclusion: This study developed a sodium hyaluronate-based soluble sufentanil microneedle patch with strong mechanical properties and rapid dissolution, which demonstrated effective analgesic efficacy in a model of breast cancer bone metastasis pain, demonstrating its potential as a novel delivery strategy for the future management of breakthrough cancer pain.