Peripheral artery disease (PAD) affects over 200 million people worldwide and can result in life-threating complications. Currently, drug-coated balloons (DCBs) are used to treat lesions in the peripheral arteries. However, commercially available DCBs are designed to treat only a single blockage site. In PAD patients, complex lesions involving long, diffuse, and/or multiple blockages are often found resulting in the use of multiple DCBs. With each DCB being very expensive and the procedure time consuming, there is a need in the market for a multiple-release DCB that can release the drug at multiple arterial locations which can reduce the number of DCBs needed for a procedure. This will ultimately result in the reduction of cost, time, and complications of DCB procedures involving complex lesions. A single release DCB was recently developed by Tailored Medical Devices, Inc. using polyethylene oxide (PEO) as a platform to control the release of the drug paclitaxel (PAT). The developed PEO balloon has shown to be safe and effective in a pre-clinical setting for the treatment of a single blockage. With modifications in the single-release PEO balloon formulation and coating strategy, a multiple-release PEO DCB (MR-PEO- DCB) has been developed. A recent pilot study showed that equivalent drug uptake and retention can be achieved in two arteries using a MR-PEO DCB. The goal of this project is to develop a sterile and biocompatible MR-PEO-DCB that can deliver PAT for the treatment of complex lesions and investigate the reproducibility of the drug retention in two different arterial locations for up to 7 days using a porcine model. Specific Aim 1: Develop reproducible and sterile MR-PEO-DCBs in a cGMP facility The MR-PEO-DCBs will be developed in a GMP facility through the use of sterile instruments and solutions used to produce the formulations. The physical, thermal, chemical, and drug-release properties of the MR- PEO-DCB coating will be tested using imaging, calorimetric techniques, and an established in vitro flow model. The developed devices will then be tested for sterility according to established USP testing methods. Specific Aim 2: Test the cytotoxicity and hemocompatibility of the MR-PEO-DCB The cytotoxicity and hemocompatibility testing will be conducted as per the FDA guidelines for the short exposure (< 24 h) blood circulation devices. Cyotoxicity, hemolysis, and complement activation will be assessed by the exposure of the device or its extracts to the appropriate cell lines. Specific Aim 3: Test the drug retention and plasma drug levels after MR-PEO-DCB treatments in vivo In vivo swine studies will be performed to test the reproducibility of drug retention at day-1 and day-7. A successful outcome of this proposal will be to develop a sterile and biocompatible multiple-release DCB that can obtain therapeutic and equivalent amounts of drug in two arterial locations. Future phase II studies would include long-term animal studies on tissue retention and healing responses.
Project Terms: Affect; Aftercare; Amputation; Animals; antiproliferative drugs; Arterial Fatty Streak; Arteries; Balloon Angioplasty; biomaterial compatibility; Blood; Blood Circulation; Cell Line; Chemicals; Cicatrix; Clinical Research; Complement; Complement Activation; Complex; cost; cytotoxic; cytotoxicity; cytotoxicity test; design; Devices; Diffuse; Dissection; Drug Delivery Systems; drug testing; effective therapy; elastomeric; Erythrocytes; Excipients; Family suidae; Fibroblasts; Formulation; Foundations; Future; Goals; Guidelines; healing; Hemolysis; Human; Hydrophobicity; Image; improved; In Vitro; in vivo; innovation; instrument; Kidney Failure; Lesion; Licensing; Life; Location; Measures; Medical; Medical Device; Methods; Miniature Swine; Modeling; Modification; multiple drug use; Mus; Myocardial Infarction; new technology; novel therapeutics; Operative Surgical Procedures; Outcome; Paclitaxel; Pain; Particulate; Patients; Perforation; Peripheral; Peripheral arterial disease; Pharmaceutical Preparations; Phase; phase 2 study; Pilot Projects; Plasma; Polyethylene Glycols; pre-clinical; Procedures; Process; Property; Publishing; Reproducibility; response; restenosis; Role; Serum; Site; Small Business Innovation Research Grant; Sterility; sterility testing; Stroke; Syringes; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Treatment Cost; United States; uptake; Work;
