Respiratory diseases represent a significant public health challenge owing to their frequency and challenges in treatment. In particular, pulmonary fibrosis (PF) occurs when lung tissue becomes damaged and scarred and the thickened, stiff tissue decreases lung function so that afflicted patients become more progressively short of breath. Idiopathic pulmonary fibrosis (IPF), in which the cause of the disease is unknown, is on the rise and is projected to impact more than 17 per 100,000 persons in the U.S. in the near future.1 IPF is a particularly deadly form of the disease involving chronic, progressive fibrosis of the lungs. IPF is highly variable and unpredictable, and treatment options for this disease are limited, and none are curative.2 Due to the lack of effective treatments, this condition is characterized by a median life expectancy of about 3 years and until the last decade, lung transplantation was the only option available to alter the course of this disease. In 2014, two anti-fibrotic drugs, pirfenidone and nintedanib, were approved by the FDA for treatment as they were shown to slow down functional decline and progression of IPF.3 However, the effects of these drugs are moderate as they do not reverse disease progression and cause severe adverse skin and gastrointestinal effects due to high, chronic dosing and non-specific, inefficient delivery to the lungs.2,4 In addition, these drugs are limited by a repetitive treatment regimen requiring multiple daily doses to ensure efficacy. Therefore, there is an urgent need for more effective therapeutics in addition to more effective methods/carriers to deliver PF-related drugs to the lungs. Thus, the objective of this proposal is to develop and validate particle-based therapeutics based on cell membrane-coated nanoparticles (CMCNP) for the attenuation of pulmonary fibrosis via the following Specific Aims:

Aim 1. Formulate platelet membrane coated-nanoparticles (PCNP) containing various therapeutics and evaluate their physicochemical and in vitro properties.

1. Formulate PCNP and evaluate their physicochemical and cell membrane properties.
2. Analyze in vitro NP internalization, binding, and toxicity in PF-related cells and collagen-NP binding.

Aim 2. Investigate the biodistribution and efficacy of PCNP as drug delivery vehicles for the attenuation of mouse model of PF.

1. Determine the biodistribution of PCNP in the bleomycin-induced lung fibrosis model.
2. Evaluate the efficacy of PCNP using the bleomycin-induced lung fibrosis model.