Yeo lab:Projects

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One of the major obstacles in translating potent drug candidates from bench to bedside is their spatiotemporally adequate delivery. For example, small interfering RNA (siRNA) has been recognized as a promising new class of drugs for viral infections, neurodegenerative diseases, and cancer; however, its therapeutic potential has not been realized because of the instability in circulation and inefficient delivery to the target cells. Target-specific delivery of anti-cancer drugs with minimal side effects on normal tissues has long been a goal for cancer therapy, but their clinical application remains challenging.  
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We strive to make a significant impact in public health through research. The goal of our research is to develop new drug delivery systems and biomaterials, which will enable a safe, efficient, and clinically viable delivery of drugs, genes, and/or cells in a target-specific manner.  
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We are interested in developing drug/gene delivery systems which can address these challenges in ‘delivery.’ Research projects will focus on i) addressing the obstacles in siRNA delivery using formulation approaches, (ii) developing nanoparticles which mimic leukocyte-rolling behavior for tumor targeting, and (iii) developing inhalable microparticles which allows for delivering combinations of drugs for cystic fibrosis therapy.  
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== Tumor Targeted Drug Delivery ==
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In developing safe and effective chemotherapy, it is critical to engineer a targeted drug delivery system that can selectively deliver cytotoxic drugs to tumor cells without affecting normal cells. While extensive efforts are made to enhance recognition of the drug carriers by tumor tissues (i.e., “active targeting”), the targeting effect is mostly achieved by the enhanced permeability and retention (EPR) effect, irrespective of the strategy. The limited success of the active targeting strategy is due in part (i) to the diversity and heterogeneity of the tumor cells and (ii) to the fact that the tumor cells expressing the target molecules may not necessarily be exposed to circulating nanocarriers. We hypothesize that nanocarriers can be designed in such a way that they remain inert in normal tissues but are activated to a cell-interactive form in a tumor-specific manner.  Our laboratory is utilizing common microenvironmental features of tumors, such as a high level of proteinases and weakly acidic pH, as molecular cues to trigger activation of the nanocarriers.  
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Under construction... more to come...
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== Inhalational Drug Delivery for Chronic Pulmonary Diseases ==
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Inhalable microparticles are an attractive treatment option for chronic pulmonary diseases such as cystic fibrosis, asthma, or chronic obstructive pulmonary disease, because they can provide efficient local medication with minimal systemic side effects, a prolonged therapeutic effect, and an easy way of administration. Recent advances in particle technology have overcome a number of hurdles in achieving microparticles with favorable aerodynamic properties. However, existing technologies do not adequately address biological barriers specific to the pulmonary diseases. We recognize that mucus layer on the lung epithelium is a significant barrier for pulmonary drug delivery, especially in therapy of cystic fibrosis and obstructive lung diseases. When this barrier is effectively overcome, inhalational drug delivery systems will open up new opportunities for these devastating diseases. With this challenge in mind, our laboratory has recently produced and evaluated a spray-dried powder containing both DNase and ciprofloxacin. We now have a proof of principle that simultaneous delivery of a drug along with a mucolytic agent can facilitate diffusion of the drug and enhance its efficacy and, consequently, reduce the dose requirement for inhaled powder. Our goal is to extend this principle to develop inhalable gene delivery system consisting of mucolytic sugars and a new gene-polymer complex recently developed in our lab for gene therapy of cystic fibrosis.
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==Biomaterials and Drug Delivery Systems for Functional Repair of Damaged Tissues ==
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Two research endeavors are made in the area of in-situ tissue regeneration. One is to engineer functional cardiac tissues in situ by delivering microencapsulated growth factors and cardiomyocytes using an in-situ crosslinkable hydrogel. The lack of success in cell therapy of myocardial infarction (MI) is attributed to the significant cell loss following transplantation, resulting from limited cell survival and maintenance of surviving cells. We hypothesize that timely supply of essential combinations of growth factors will improve the survival and functional development of implanted cardiomyocytes and increase the success rate of the cell-based MI therapy. The other application is to utilize the in-situ crosslinkable hydrogel for assisting in fusion of severed spinal cords. While no effective therapies to treat nerves that are completely severed currently exist, it is shown that function of transected nerves can be immediately restored ex vivo by application of polyethylene glycol.  However, the nerve repair technique has not been successful in vivo. One of the reasons may be that the bond reconnecting nerves is easily damaged by tissue micromotion. We hypothesize that a bioadhesive chitosan hydrogel would stabilize the severed nerves and facilitate functional recovery.
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Current revision

Laboratory for Therapeutic Particle Engineering

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We strive to make a significant impact in public health through research. The goal of our research is to develop new drug delivery systems and biomaterials, which will enable a safe, efficient, and clinically viable delivery of drugs, genes, and/or cells in a target-specific manner.

Tumor Targeted Drug Delivery

In developing safe and effective chemotherapy, it is critical to engineer a targeted drug delivery system that can selectively deliver cytotoxic drugs to tumor cells without affecting normal cells. While extensive efforts are made to enhance recognition of the drug carriers by tumor tissues (i.e., “active targeting”), the targeting effect is mostly achieved by the enhanced permeability and retention (EPR) effect, irrespective of the strategy. The limited success of the active targeting strategy is due in part (i) to the diversity and heterogeneity of the tumor cells and (ii) to the fact that the tumor cells expressing the target molecules may not necessarily be exposed to circulating nanocarriers. We hypothesize that nanocarriers can be designed in such a way that they remain inert in normal tissues but are activated to a cell-interactive form in a tumor-specific manner. Our laboratory is utilizing common microenvironmental features of tumors, such as a high level of proteinases and weakly acidic pH, as molecular cues to trigger activation of the nanocarriers.

Inhalational Drug Delivery for Chronic Pulmonary Diseases

Inhalable microparticles are an attractive treatment option for chronic pulmonary diseases such as cystic fibrosis, asthma, or chronic obstructive pulmonary disease, because they can provide efficient local medication with minimal systemic side effects, a prolonged therapeutic effect, and an easy way of administration. Recent advances in particle technology have overcome a number of hurdles in achieving microparticles with favorable aerodynamic properties. However, existing technologies do not adequately address biological barriers specific to the pulmonary diseases. We recognize that mucus layer on the lung epithelium is a significant barrier for pulmonary drug delivery, especially in therapy of cystic fibrosis and obstructive lung diseases. When this barrier is effectively overcome, inhalational drug delivery systems will open up new opportunities for these devastating diseases. With this challenge in mind, our laboratory has recently produced and evaluated a spray-dried powder containing both DNase and ciprofloxacin. We now have a proof of principle that simultaneous delivery of a drug along with a mucolytic agent can facilitate diffusion of the drug and enhance its efficacy and, consequently, reduce the dose requirement for inhaled powder. Our goal is to extend this principle to develop inhalable gene delivery system consisting of mucolytic sugars and a new gene-polymer complex recently developed in our lab for gene therapy of cystic fibrosis.

Biomaterials and Drug Delivery Systems for Functional Repair of Damaged Tissues

Two research endeavors are made in the area of in-situ tissue regeneration. One is to engineer functional cardiac tissues in situ by delivering microencapsulated growth factors and cardiomyocytes using an in-situ crosslinkable hydrogel. The lack of success in cell therapy of myocardial infarction (MI) is attributed to the significant cell loss following transplantation, resulting from limited cell survival and maintenance of surviving cells. We hypothesize that timely supply of essential combinations of growth factors will improve the survival and functional development of implanted cardiomyocytes and increase the success rate of the cell-based MI therapy. The other application is to utilize the in-situ crosslinkable hydrogel for assisting in fusion of severed spinal cords. While no effective therapies to treat nerves that are completely severed currently exist, it is shown that function of transected nerves can be immediately restored ex vivo by application of polyethylene glycol. However, the nerve repair technique has not been successful in vivo. One of the reasons may be that the bond reconnecting nerves is easily damaged by tissue micromotion. We hypothesize that a bioadhesive chitosan hydrogel would stabilize the severed nerves and facilitate functional recovery.

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