Tolerogenic cargo delivery via polymeric microparticles in reducing autoimmune-specific inflammation

s are below: 2019 Mid-Atlantic Biomaterials Day February 23, 2019 Translational Biomaterials: Closing the Gap from Bench to Bedside Saturday February 23rd, 2019 From 10 AM to 5 PM University of Maryland, College Park A. James Clark Hall 8278 Paint Branch Dr., College Park, MD 20740 Keynote Address Dr. Chris Jewell – University of Maryland , College Park Speakers Dr. Emily English – Gemstone Therapeutics Dr. Stephen Horrigan – Noble Life Sciences Dr. Qijin Lu – US FDA Dr. Hai-Quan Mao – Johns Hopkins Sean Virgile – Diagnostic anSERS Inc. Leah Kesselman – Rheolution Inc. Networking Opportunities! Prizes for Best Research! Catered Food! Hosted by the SFB Chapters at University of Maryland and Johns Hopkins To submit an abstract or register for tickets, visit: https://midatlanticbiomaterialsday 2019.squarespace.com We are now accepting abstracts for rapid fire talks and posters for the 3rd annual Mid-Atlantic Biomaterials Day! Nanoparticle Multi-Drug Delivery Platform for the Treatment of Breast Cancer Kisha Patel, Dr. Stephany Tzeng, Dr. Jordan Green Johns Hopkins University Whiting School of Engineering, Johns Hopkins Medical Institute Wilmer Eye Institute Statement of Purpose: Breast cancer (BC) is the second leading cause of cancer related death in the United States. Every year there are over 200 thousand new cases of BC and approximately 40 thousand BC deaths annually in the United States alone. [1] BC is particularly deleterious because of its potential to metastasize and spread through the circulatory system. The key challenges in BC research are gaining the ability to selectively target tumor cells without harming healthy cells, improving the ease of application of the treatment, reducing the required frequency of the treatment, and personalizing treatments to suit the patients’ individual needs, such as the stage of cancer development. In order to overcome these challenges, a systemic nanoparticle multidrug delivery system is required, which would allow for the administration of various therapeutic agents via a subcutaneous injection to facilitate a multifaceted treatment plan. The backbone of this platform relies on the Enhanced Permeability and Retention (EPR) effect which allows for increased accumulation and release of nanoparticles and agents at the tumor site. Anti-Hypoxia Inducing Factors (anti-HIF) agents will be use do decrease the ability of the tumor tissue to promote angiogenesis. Such agents include doxorubicin, acriflavine, and digoxin.[3] In order to increase the serum half-life of such therapeutic agents, we propose encapsulating each drug in nanoparticles made of a triblock co-polymer of poly(lactic-coglycolic acid) (PLGA) and poly(ethylene glycol) (PEG). PEG would increase the half-life by coating the nanoparticle, thus decreasing uptake by macrophages and other surveillance cells and PLGA would allow for a sustained release kinetics which allows for fewer individual doses to be administered. Methods: PLGA is the primary polymer to be used because it is a component of many FDA-approved devices and applications and has been proven to have low immunogenicity.[2] Its hydrophobicity can be altered to alter release kinetics of the therapeutic agents therefore allowing increased freedom in optimization of a treatment regimen for patients with varying degrees of cancer progression. The nanoparticles are fabricated through a nanoprecipitation process in which the polymer is dissolved in a water-miscible solvent, such as DMSO, and the drug is dissolved in another water-miscible solvent, such as acetone, and they are mixed and added to an aqueous poly(vinylalcohol) (PVA) solution under sonication. These components are then placed on a stir plate for three hours for the particles to harden and the organic solvents to diffuse away or evaporate. The release of the drugs from the particles has also been studied and is important in understanding the length of time of effective treatment. The particles will be optimized to release for a two-week window. Cell studies have already been done to verify the biological effect of these therapeutic agents on HIF-1 signaling. After the optimization of the nanoparticle coating and dosage levels, they are injected via the tail vein into mice to better understand the biodistribution of the particles in the body. This can be done through the use of an In Vivo Imaging System (IVIS) and fluorescence measurements of blood samples taken at various time points from the treated mice. Because the particles are also loaded with Cy7.5 fluorescent dye, we will be able to track the circulation of the particles within the mouse body. The fluorescence of each major organ and tumor is analyzed in order to understand the accumulation of the nanoparticles in the body. Results: The size of the fabricated nanoparticles was analyzed by dynamic light scattering (DLS). The optimal diameter of these particles is under 200 nm to prevent blockage in blood vessels and to exploit the EPR effect was reached. Biodistribution studies were also performed and showed upwards of 15% accumulation at the tumor site which is significant. Conclusions: The nanoparticle synthesis process has been optimized and methods to increase targeted accumulation of particles are underway. In order to increase the longevity of the particles in the circulatory system, a red blood cell coating can also be added to avoid immune surveillance. In the future, the loading of digoxin, an anti-HIF agent, must be optimized. Digoxin is about a hundred-fold more potent than doxorubicin and acriflavine, therefore increasing the need to optimize its encapsulation efficacy.[3] Acriflavine biodistribution studies will also be essential in understanding how effective the treatment method is. This will be performed within upcoming months. All biodistribution studies will also have to be repeated with a larger sample size. Once biodistribution studies have been completed, the nanoparticles will be injected in varying combinations in order to optimize the treatment and the tumor regression will be tracked through IVIS imaging, protein assays to analyze HIF activity, etc. References: [1] Ma J., Jemal A. (2013) Breast Cancer Statistics. In: Ahmad A. (eds) Breast Cancer Metastasis and Drug Resistance. Springer, New York, NY. [2] Jain R. (2000) The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials. 21(23): 2475-2490. [3] Zhang H. (2008) Digoxin and other cardiac glycosides inhibit HIF-1α synthesis and block tumor growth. PNAS. 105(50): 19579-19586. Inkjet-Printed Scalable Electrocorticography Sensor Alana Tillery1, Jia Hu2, Mathew Rynes2, Suhasa B. Kodandaramaiah2,3 1 Department of Bioengineering, University of Maryland, College Park, MD 2 Department of Biomedical Engineering, University of Minnesota, Twin Cities, MN 3 Department of Mechanical Engineering, University of Minnesota, Twin Cities, MN Statement of Purpose: Brain-computer interfaces (BCI) have vast potential to augment and repair cognitive ability. Further, a class of BCI device which measures neural activity by flexibly conforming to the 3D topology of the brain is the electrocorticogram (ECoG) electrode array. Neural interfacing utilizing electrocorticography (ECoG) devices has been used to restore communication to individuals affected by latestage amyotrophic lateral sclerosis [1] and to control a prosthetic limb [2]. In a minimally invasive manner, placement of ECoG arrays directly on the cortical surface avoids the diminished biocompatibility of implanting needle-like penetrating electrodes [3] while coupling high-resolution neural signal acquisition. The literature supports fabrication of an ECoG array requires microfabrication techniques, which can prove an insurmountable expense and barrier to entry into ECoG research [4]. To lessen the use of remote techniques, inkjet printing of conductive traces [5] and use of few microfabrication techniques has been published in the context of customizable, flexible neural interfaces [6]. In this work, we present a novel desktop ECoG array fabrication process entirely using commonly available desktop laboratory tools. We characterized arrays by conducting in vivo experiments in mouse models. Methods: We began electrode array fabrication with 1) inkjet printing conductive electrode designs using silver nanoparticle (AgNP) ink on photo paper (Fig.2), as described in the literature [5]. To increase the biocompatibility and improve the neural signal acquisition of the AgNP traces, we 2) added a protective layer of the conductive biopolymer polyethylene dioxythiophene polystyrene sulfonate (PEDOT:PSS) [6] and sintered the AgNPs and PEDOT:PSS at 135°C. Through 3) coating the electrode traces between the rectangular pads and circular contacts with UV-curable polymethyl methacrylate (PMMA) and subsequent UVtreatment, we prevented interelectrode shorting and increased the durability and adhesion while maintaining the flexibility of the array. The durability of printed ECoG arrays was measured by a) mimicking neural conditions by immersing arrays in 1x phosphate-buffered saline (PBS) solution for five days as described previously [7] for a satisfactory electrochemical impedance of under 1 MΩ [3] at a sampling frequency of 1 kHz and b) adhering Scotch tape and a 200 g mass to the array as published previously as an adhesion test[8] and upon pull-off assessing endurance of the electrodes against delamination. To collect neural signals in vivo, we designed a custom 12-channel printed circuit board (PCB) with a molex connection and clamping mechanism to interface with an amplifier. Results: Following five-day submergence in 1x PBS, electrode arrays had a range of impedances of 0.876 – 3.11 kΩ. After the Scotch tape adhesion test, arrays showed limited fracturing or discontinuities in Ag nano and PEDOT:PSS traces. We conducted in vivo experiments with head-fixed mice anesthetized