An official website of the United States government
Tracheobronchial tumors, while uncommon, are often malignant in adults. Surgical removal is the primary therapy for non-metastatic lung malignancies, but it is only possible in a small percentage of non-small-cell lung cancer patients and is limited by the number and location of tumors, as well as the patient’s overall health. This study proposes an alternative treatment: administering aerosolized chemotherapeutic particles via the pulmonary route using endotracheal catheters to target lung tumors. To improve delivery efficiency to the lesion, it is essential to understand local drug deposition and particle transport dynamics. This study uses an experimentally validated computational fluid particle dynamics (CFPD) model to simulate the transport and deposition of inhaled chemotherapeutic particles in a 3-dimensional tracheobronchial tree with 10 generations (G). Based on the particle release maps, targeted drug delivery strategies are proposed to enhance particle deposition at two lung tumor sites in G10. Results indicate that controlled drug release can improve particle delivery efficiencies at both targeted regions. The use of endotracheal catheters significantly affects particle delivery efficiencies in targeted tumors. The parametric analysis shows that using smaller catheters can deliver more than 74% of particles to targeted tumor sites, depending on the location of the tumor and the catheter diameter used, compared to less than 1% using conventional particle administration methods. Furthermore, the results indicate that particle release time has a significant impact on particle deposition under the same inhalation profile. This study serves as a first step in understanding the impact of catheter diameter on localized endotracheal injection for targeting tumors in small lung airways.
more »
« less
A user-centered smart inhaler algorithm for targeted drug delivery in juvenile onset recurrent respiratory papillomatosis treatment integrating computational fluid particle dynamics and machine learning
Recurrent respiratory papillomatosis (RRP) is a chronic condition primarily affecting children, known as juvenile onset RRP (JORRP), caused by a viral infection. Antiviral medications have been used to reduce the need for frequent surgeries, slow the growth of papillomata, and prevent disease spread. Effective treatment of JORRP necessitates targeted drug delivery (TDD) to ensure that inhaled aerosolized drugs reach specific sites, such as the larynx and glottis, without harming healthy tissues. Using computational fluid particle dynamics (CFPD) and machine learning (ML), this study (1) investigated how drug properties and individual factors influence TDD efficiency for JORRP treatment and (2) developed personalized inhalation therapy using an ML-empowered smart inhaler control algorithm for precise medication release. This algorithm optimizes the inhaler nozzle position and diameter based on drug and patient-specific data, enhancing drug delivery to the larynx and glottis. CFPD simulations show that particle size significantly affects deposition fractions in the upper airway, emphasizing the importance of particle size selection. Additionally, optimal nozzle diameter and delivery efficiency depend on particle size, inhalation flow rate, and release time. The ML-based TDD strategy, employing a classification and regression tree model, outperforms conventional inhalation therapy by achieving a higher delivery efficiency to the larynx and glottis. This innovative concept of an ML-empowered smart inhaler represents a promising step toward personalized and precise pulmonary healthcare through inhalation therapy. It demonstrates the potential of AI-driven smart inhalers for improving the treatment outcomes of lung diseases that require TDD at designated lung sites.
more »
« less
- Award ID(s):
- 2120688
- PAR ID:
- 10507965
- Publisher / Repository:
- AIP Publishing
- Date Published:
- Journal Name:
- Physics of Fluids
- Volume:
- 36
- Issue:
- 2
- ISSN:
- 1070-6631
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
This article belongs to the Special Issue Hydrogels with Appropriate/Tunable Properties for Biomedical Applications (Ed.)Pulmonary drug delivery via microspheres has gained growing interest as a noninvasive method for therapy. However, drug delivery through the lungs via inhalation faces great challenges due to the natural defense mechanisms of the respiratory tract, such as the removal or deactivation of drugs. This study aims to develop a natural polymer-based microsphere system with a diameter of around 3 μm for encapsulating pulmonary drugs and facilitating their delivery to the deep lungs. Pectin was chosen as the foundational material due to its biocompatibility and degradability in physiological environments. Electrospray was used to produce the pectin-based hydrogel microspheres, and Design-Expert software was used to optimize the production process for microsphere size and uniformity. The optimized conditions were determined to be as follows: pectin/PEO ratio of 3:1, voltage of 14.4 kV, distance of 18.2 cm, and flow rate of 0.95 mL/h. The stability and responsiveness of the pectin-based hydrogel microspheres can be altered through coatings such as gelatin. Furthermore, the potential of the microspheres for pulmonary drug delivery (i.e., their responsiveness to the deep lung environment) was investigated. Successfully coated microspheres with 0.75% gelatin in 0.3 M mannitol exhibited improved stability while retaining high responsiveness in the simulated lung fluid (Gamble’s solution). A gelatin-coated pectin-based microsphere system was developed, which could potentially be used for targeted drug delivery to reach the deep lungs and rapid release of the drug.more » « less
-
Recently, nano-based cancer therapeutics have been researched and developed, with some nanomaterials showing anticancer properties. When it comes to cancer treatment, graphene quantum dots (GQDs) contain the ability to generate 1O2, a reactive oxidative species (ROS), allowing for the synergistic imaging and photodynamic therapy (PDT) of cancer. However, due to their small particle size, GQDs struggle to remain in the target area for long periods of time in addition to being poor drug carriers. To address this limitation of GQDs, hollow mesoporous silica nanoparticles (hMSNs) have been extensively researched for drug delivery applications. This project investigates the utilization and combination of biomass-derived GQDs and Stöber silica hMSNs to make graphene quantum dots-hollow mesoporous silica nanoparticles (GQDs-hMSNs) for fluorescent imaging and dual treatment of cancer via drug delivery and photodynamic therapy (PDT). Although the addition of hMSNs made the newly synthesized nanoparticles slightly more toxic at higher concentrations, the GQDs-hMSNs displayed excellent drug delivery using fluorescein (FITC) as a mock drug, and PDT treatment by using the GQDs as a photosensitizer (PS). Additionally, the GQDs retained their fluorescence through the surface binding to hMSNs, allowing them to still be used for cell-labeling applications.more » « less
-
Patient management is not based on a single decision. Rather, it is dynamic: based on a sequence of decisions, with therapeutic adjustments made over time. Adjustments are personalized: tailored to individual patients as new information becomes available. However, strategies allowing for such adjustments are infrequently studied. Traditional antibiotic trials are often nonpragmatic, comparing drugs for definitive therapy when drug susceptibilities are known. COMparing Personalized Antibiotic StrategieS (COMPASS) is a trial design that compares strategies consistent with clinical practice. Strategies are decision rules that guide empiric and definitive therapy decisions. Sequential, multiple-assignment, randomized (SMART) COMPASS allows evaluation when there are multiple, definitive therapy options. SMART COMPASS is pragmatic, mirroring clinical, antibiotic-treatment decision-making and addressing the most relevant issue for treating patients: identification of the patient-management strategy that optimizes the ultimate patient outcomes. SMART COMPASS is valuable in the setting of antibiotic resistance, when therapeutic adjustments may be necessary due to resistance.more » « less
-
Abstract Chronic wounds present significant therapeutic challenges due to prolonged inflammation and bacterial infections, impeding healing. Conventional medicinal dressings typically deliver a single drug with a fixed release profile and lack responsiveness to variations in wound size, nature, or severity. This study introduces an innovative microneedle (MN) patch designed with different microneedle geometries and capable of dual‐drug delivery to address irregular wounds and complex therapeutic requirements. Utilizing CO₂ laser lithography, microneedle molds are fabricated with diverse geometries by precisely controlling laser parameters such as speed, power, and focus, achieving needle heights ranging from 162 ± 30 µm to 1570 ± 40 µm. The patch facilitates simultaneous delivery of simvastatin (SIM) for anti‐inflammatory and tetracycline hydrochloride (TH) for antibacterial properties, targeting different skin depths. In vitro diffusion studies confirm geometry‐dependent drug release profiles, with SIM achieving controlled release over three days and TH exhibiting sustained release over four days. Biocompatibility assays confirmed safety and enhanced fibroblast migration is noted in wound‐healing studies. Antimicrobial testing reveals a 99.9% reduction in bacterial viability. This cost‐effective and scalable approach enables precise, localized delivery and customization of MN arrays to match various wound geometries, offering a versatile platform for personalized medicine and improved chronic wound management.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1063/5.0186786
