AIChE 2015 Annual Student Conference
November 7th, 2015
“Evaluating Nanocomposite Microparticles for the Delivery of Therapeutics for Pulmonary Arterial Hypertension”
Julie L. Cuddigan1, Zimeng Wang1, Samantha A. Meenach1,2
1Department of Chemical Engineering, 2Department of Biomedical & Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881
Pulmonary arterial hypertension (PAH) is a chronic, incurable, and life-threatening disease that is characterized by abnormally high blood pressure in the arteries leading from the heart to the lungs. Patients with PAH often suffer from chest pain, shortness of breath, fainting, dizziness, and in many cases experience heart failure and ultimately death. The therapies currently approved to treat PAH are most commonly available in oral or intravenous form, but often result in undesirable systemic side effects. An effective treatment needs to be designed to deliver targeted therapeutics to the lung periphery to ensure maximum localized bioavailability and to decrease the side effects associated with systemic delivery. The goal of our research is to develop and evaluate dry powder aerosols comprised of nanocomposite microparticles (nCmP) containing the newly-investigated PAH drug tacrolimus to be delivered directly to the lung and surrounding arteries. These particles are designed to overcome mucociliary clearance in the lung and to avoid alveolar macrophages to allow for longer retention time in the lungs. The production of these aerosols began with synthesizing the biodegradable polymer, acetalated dextran (Ac-Dex), with an appropriate cyclic acetal conversion (65-75%). Then using a single emulsion evaporation method, Ac-Dex was used in the formation of drug-loaded nanoparticles, which were characterized for their size, charge, and drug encapsulation. The final step of synthesizing the nCmP consisted of spray drying a suspension of nanoparticles in mannitol (the excipient) and water. The nCmP were characterized for their size, morphology, drug loading, water content, and aerodynamic properties. The nanoparticles were successfully optimized to be of appropriate size to avoid macrophage uptake (150 - 230 nm). The drug-loaded particles had an encapsulation efficiency of 69.3%, resulting in a drug loading of 70.4 μg tacrolimus/mg nanoparticles. The spray dried nCmP were 2.1 μm in diameter and exhibited a mass median aerodynamic diameter of 3.6 μm, which is appropriate for deep lung deposition. The nCmP had less than 10% water content and tacrolimus encapsulation efficiency of 62.8%, resulting in a drug loading of 31.9 μg tacrolimus/mg nCmP. The development of the aforementioned nCmP could lead to the improved treatment of PAH for many patients afflicted by this life-threatening disease.
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