Development of Highly Porous Large Polymeric Microparticles for Sustained Local Drug Delivery to the Lung
Inhalable dry-powder systems are an attractive modality for the treatment of many pulmonary disorders, such as cystic fibrosis, asthma, airway and pulmonary infections, pulmonary hypertension, and lung cancers. For these diseases, targeted medication delivery to the lung is highly desirable because it results in effective drug concentrations at the site of the pathology with minimal systemic toxicity. For effective intrapulmonary drug delivery physical properties of the particles are crucial. First, the optimal particle size for adults or older children should fall within the range of 1-5 µm. Second, for the powders to provide the sustained local effect, they should avoid phagocytosis by alveolar macrophages. Unfortunately, the particle size range optimal for inhalation (1-5 µm) is also ideal for phagocytosis. Third, while ideal dry-powder particles should maintain the same aerodynamic diameter during storage, particles with a mean diameter of 1-5 µm tend to agglomerate. Large porous microparticles, characterized by large geometric diameters but low density and small aerodynamic diameters, have been explored to address these conflicting requirements. Such microparticles could be produced by different methods including spray-drying or the double emulsion method, with excipients or additional procedures to increase the porosity and size of the particles. While these methods may provide particles with favorable physical properties for inhalation, many limitations still exist, especially if sustained pulmonary drug delivery is intended. Spray-dried particles composed of a mixture of drug and excipients imparting aerodynamic properties do not control drug release well enough to provide sustained effects. Polymeric microparticles may control drug release better; however, the use of porogenic excipients compromises the drug encapsulation efficiency.
In this presentation, I will introduce a new way of making highly porous large polymeric microparticles recently developed in my lab. These microparticles exhibited desirable aerodynamic properties, reduced macrophage uptake, encapsulated a drug efficiently, and provided sustained drug release over 12 hours. This is a simple and efficient method of producing highly porous large particles, which are a promising drug carrier for local inhalational therapy of pulmonary infections often associated with chronic lung disorders, such as cystic fibrosis.
Dr. Yeo has published 25 peer-reviewed papers and 4 book chapters in these fields and received various awards from professional organizations including CRS-3M Drug Delivery Systems Graduate Student/Post-Doc Outstanding Drug Delivery Paper Award (2003) and AAPS Outstanding Graduate Student Research Award in Pharmaceutical Technologies (2004). Dr. Yeo has 2 U.S. Patents and 2 pending patents.
Since her arrival at Purdue in January 2007, she has established an interdisciplinary research program that focuses on engineering therapeutic particles for drug delivery and tissue engineering. As of spring 2008, 12 researchers (1 post-doctoral, 3 graduate, 2 visiting scholars, and 6 undergraduate students) are working in her lab. Dr. Yeo’s research interest spans three areas: (i) Microparticle engineering for pulmonary drug delivery, which is funded by the Cystic Fibrosis Foundation and 3M Drug Delivery Systems; (ii) Developing microcapsules and hydrogels for tissue engineering applications; and (iii) Nanoparticle engineering for tumor-targeted delivery of therapeutic agents. She is actively exploring domestic and international collaboration with physicians, engineers, and industrial researchers.
Researchers should cite this work as follows:
Centre for Cellular and Molecular Biology, Hyderabad, India