Poster N4 - Precision Drug Delivery Using Near-Infrared Activated Ethyl Cellulose Micro/Nanoparticles

Introduction: Drug delivery systems are a key part of modern medical research, especially for treating tough diseases like cancer and neurological disorders. Current treatments often harm healthy cells, highlighting the need for more targeted delivery methods. Microparticles and nanoparticles (MPs/NPs), have shown promise for precise drug delivery because they can be made in different ways and have adjustable properties. This study focuses on creating, testing, and evaluating ethyl cellulose (EC) MPs/NPs as effective drug carriers, enhanced by adding materials that respond to specific triggers to control drug release. EC polymer is known to be biocompatible 𝑖𝑛 𝑣𝑖𝑣𝑜 with relatively low immune reaction, substantiated by the superiority in attachment, and viability. Due to their biocompatibility, EC has been used in the fabrication of films, microspheres, and microcapsules. In general, EC microspheres are a helpful material because of their capability to boost the performance of active ingredients, their adaptability, and the control that they have over the release of drugs and other active components. Stimulus responsive materials, such as silver NPs and Indocyanine Green were added to further control drug release. While various stimuli can be used, this paper focuses on the use of Near Infrared Light (NIR) to accelerate drug release.

Materials and

Methods: Poly (vinyl alcohol) (PVA) (87-90% hydrolyzed with an avg. molecular weight of 30,000-70,000), dichloromethane (DCM), Ethyl Cellulose (EC) (48.0-49.5% (w/w) ethoxyl basis), Gentamicin Sulfate (GS), Silver (Ag) NPs, Indocyanine Green (ICG) were used for the experiments. Escherichia coli (E. coli) was used for anti-bacterial testing of MPs/NPs. The EC microparticles were fabricated using the double emulsion methodology. 1wt% EC was weighed and dissolved in nitrogen purged DCM. The solution was added dropwise to a 1% PVA dissolved in distilled water and homogenized for 3mins at ~18,000rpm. GS dissolved in distilled water was incorporated in the initial process by homogenizing to create water in oil emulsion. The NIR responsive materials were mixed with the oil phase directly as they were dissolved in organic solvents. To test for drug release from the microspheres, 10 mg of fabricated EC microspheres containing Gentamicin and NIR responsive materials were placed into a 2 ml solution of phosphate-buffered saline (PBS) with a pH of 7.4 inside a Cytivia dialysis kit with a cut-off of 8 kDa. The particles were exposed to NIR light (808nm) at different powers. The quantification of percent drug content and encapsulation efficiency for the prepared microspheres involved weighing samples of the microspheres and dissolving them in a 0.1 N HCl buffer. An antibacterial test (Kirby-Bauer Test) was conducted to qualitatively evaluate the drug release effectiveness of the microparticle. Multiple samples were tested, including differing drug concentrations and silver NP infused microparticles. All experiments were repeated three times and subsequently analyzed.

Results, Conclusions, and Discussions: The EC carriers were fabricated using a double emulsion method and are loaded with the antibiotic gentamicin, as well as materials that respond to near-infrared (NIR) light, like indocyanine green and silver NPs. The carriers are activated using a focused laser beam at 808 nm, and the results show that the drug is released faster when the carriers are exposed to NIR light. The results showed that optimum drug release at lower powers (~350mW) can also be achieved with no significant difference when compared to higher powers. Results from antibacterial experiments further substantiated the use of NIR light for quicker drug release. All samples were subjected to NIR light before the antibacterial test was conducted. The EC microparticles demonstrated various desired properties in the conducted Kirby-Bauer Tests; firstly, they demonstrated a sustained release where the antibiotic was continually being released in all time intervals, increasing the rate of release as time passes. Most importantly, the EC + Ag NPs sample subjected showed a faster rate of release supporting the idea that silver can be used as a stimulus responsive material. The physical, chemical characterization of the carriers were done using the scanning electron microscopy, infrared spectroscopy, differential scanning calorimeter, and thermal gravimetric analysis.
The main goal of this research was to develop a system that can release drugs on demand and target specific areas. To improve functionality, the carriers will further be coated with chitosan and cell-targeting peptides. The findings highlight the potential of these drug carriers to change medical treatments. Additionally, this research paves the way for more studies and improvements in this field. By showing how effective MPs/NPs are for drug delivery, this study helps advance treatments and improve patient outcomes. In the future we plan to insert the fabricated NPs into 3D printed microbots that our lab is currently working on. Furthermore, the addition of chitosan and cell targeting peptides allows for on-demand drug release and target specific therapy. The research provides a good background for the delivery of drugs and biological micro/macromolecules.

Acknowledgements (Optional): I would like to extend my deepest gratitude to Dr. Tracie Ferreira for her invaluable assistance and guidance with the bacterial experiments. Her expertise and support have been instrumental in the successful completion of this work. I would also like to express my sincere thanks to Dr. Dapeng Li for his significant contributions in the areas of Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). His insights and technical support have greatly enhanced the quality and depth of this research.