Drug delivery systems for wound healing treatment of upper airway injury

Abstract

Introduction: Endotracheal intubation is a common procedure to maintain an open airway with risks for traumatic injury. Pathological changes resulting from intubation can cause upper airway complications, including vocal fold scarring, laryngotracheal stenosis, and granulomas and present with symptoms such as dysphonia, dysphagia, and dyspnea. Current intubation-related laryngotracheal injury treatment approaches lack standardized guidelines, relying on individual clinician experience, and surgical and medical interventions have limitations and carry risks.

Areas covered: The clinical and preclinical therapeutics for wound healing in the upper airway are described. This review discusses the current developments on local drug delivery systems in the upper airway utilizing particle-based delivery systems, including nanoparticles and microparticles, and bulk-based delivery systems, encompassing hydrogels and polymer-based approaches.

Expert opinion: Complex laryngotracheal diseases pose challenges for effective treatment, struggling due to the intricate anatomy, limited access, and recurrence. Symptomatic management often requires invasive surgical procedures or medications that are unable to achieve lasting effects. Recent advances in nanotechnology and biocompatible materials provide potential solutions, enabling precise drug delivery, personalization, and extended treatment efficacy. Combining these technologies could lead to groundbreaking treatments for upper airways diseases, significantly improving patients' quality of life. Research and innovation in this field are crucial for further advancements.

Keywords: Drug delivery; biomaterials; endotracheal intubation; larynx; nanotechnology; trachea; vocal folds; wound healing.

Figure 1.

(a) Areas of potential injury along the upper airway during endotracheal intubation/extubation. Endoscopic view of (b) vocal fold scarring, (d) laryngotracheal stenosis, and (f) laryngeal granuloma. Histological images of (c) vocal fold scarring, (e) laryngotracheal stenosis, and (g) laryngeal granuloma, which are adapted from [26,32,34]. Copyright Elsevier, Wiley, and InTechOpen. Created with BioRender.com.

Figure 2.

Localization of nanoparticle-encapsulated contents in 3T3 fibroblast cells. (a) Cellular uptake of Texas Red dye encapsulated in PLGA nanoparticles (b) Cellular uptake of FITC-HGF (c) Prolonged localization of Texas Red dye in a mouse vocal fold and table comparing the testing groups of sustained fluorescence. Adapted from [81]. Copyright Wiley.

Figure 3.

(a) Immunohistochemical analysis demonstrating improved ECM remodeling in rabbit vocal folds using HGF-HA/ALG in comparison to normal, PBS-treated, and HGF-treated groups. Tissue samples stained with hematoxylin and eosin (H&E) are shown with stains using Masson’s trichrome, collagen type I and fibronectin, where the areas were quantified by pixel density in positively stained areas. Scale bars represent 30 µm. Biomechanical evaluation shows better vocal fold functionality in (b) mucosal wave oscillations using high-speed cameras and (c) viscoelasticity changes with elastic and viscous moduli following injury and subsequent treatment in HGF-HA/ALG over normal, PBS-treated, and HGF-treated groups. The immunohistochemical analysis and mucosal wave oscillations were compared using Kruska-Wallis test with Dunns’ post hoc test, while the viscoelastic properties were compared using two-way ANOVA with Bonferroni’s post hoc test. All results were evaluated at 3 months post-injury. Adapted from [82]. Copyright Springer.

Figure 4.

(left) General schematic of electrospinning DDP and AgNPs onto a polymer-coated metal stent, with the goal of preventing trachea stenosis. (right) (a) X-ray and (b,c) endoscopic images were taken following stent implantation in a rabbit model. (d) Comparison of stent-induced granulation among harvested rabbit tracheas 10 days after implantation without a stent, with an uncoated stent, and the experimental stent coated with 3 types of polymers eluting methylprednisolone. Adapted from [103] and [132]. Copyright Elsevier and MDPI.

Figure 5.

(a) Comparing the in vitro rapamycin release for 6 weeks between the PDLGA stent and the PLLA-PCL stent. (b) Exposure to physiological conditions for 21 days demonstrates that the PDLGA stent (bottom images) degrades more than the PLLA-PCL stent (top images), eventually losing its structural integrity. The stents’ compressive strength were measured using Young’s Modulus when applied with a 1-N force. (c) Initially, the PLLA-PCL stent elicits greater stiffness. (d) After 3 weeks, a reduction of Young’s Modulus was present in both groups, but the PLLA-PCL stent maintains its cylindrical stability while the PDLGA stent completely collapses. These measurements were taken at 37°C. Adapted from [96]. Copyright Royal Society of Chemistry.