We are developing technologies to tackle some of the major problems in human health
Breast cancer is the most common malignancy among women between 20 to 59 years of age in the United States. According to the American Cancer Society, about 226,870 new cases and 39,510 deaths are associated with breast cancer annually. Current methods of breast cancer treatment are largely limited by non-specificity and toxicity.Therefore, there is a pressing need for newer and even more effective therapies. Our laboratory is harnessing nanotechnology to tackle this challenge. We synthesize pure drug nanoparticles to improve the effectiveness and specificity against breast cancer cells. We particularly focus on engineering the shape of nanoparticles to enhance their targeting ability. We expect that these shape-engineered pure drug nanoparticles willhave the potential to effectively treat breast cancer while minimizing side effects. We also develop combination drug therapies for the treatment of breast cancer. We also focus on identification of drug combinations that operate synergistically and use polymeric nanoparticles to deliver these drugs at their synergistic proportions in the tumor.
Diabetes is a highly prevalent chronic metabolic disorder which impairs body’s glucose metabolism. The Center for Disease Prevention and Control (CDC) estimates that around 26 million Americans have diabetes with an estimated mortality of 231,000 in 2007. Current therapy for diabetes primarily relies on administration of insulin by injections. However, the current therapeutic regimen has several limitations including invasive multiple injections, dose overshooting, postprandial hyperglycemia and weight gain. Our laboratory is developing approaches for oral delivery of insulin for Type I diabetes. We have developed multilayered mucoadhesive intestinal patches that enable sustained release of clinically relevant doses of insulin into the blood stream. Using the same platform, we are also exploring oral delivery of exenatide for Type II diabetes, thus facilitating a better and streamlined control over blood glucose concentration over a prolonged period of time. We have also developed technologies to allow continuous non-invasive glucose monitoring through skin as an alternative to painful finger-sticks, a technology that has advanced into the clinic.
Osteoporosis is a disease of bones resulting from drastic reduction in bone mineral density, and deteriorated bone micro-architecture, leading to an increased risk of bone fractures. Approximately 28 million individuals, primarily the elderly, have or are at the risk for osteoporosis in the U.S. Primary therapeutic regimen for osteoporosis includes injections of salmon calcitonin, a naturally occurring linear polypeptide hormone. It directly inhibits the osteoclastic bone resorption activity in bone remodeling and thus reduces the rate of bone thinning. However, this peptide has to be injected using needles. We are developing technologies to facilitate oral delivery of calcitonin by enhancing its systemic absorption across the intestine.
Cardiovascular diseases remain among the leading causes of death worldwide. Atherosclerosis, the formation of vascular plaque is a common manifestation of cardiovascular disease and can be lethal, especially when the plaque is unstable, which also acts as a risk factor for stroke. Thrombosis, including deep vein thromobosis and pulmonary embolism, are common disorders affecting about 1 in 1000 patients. A common culprit in these varied cardiovascular diseases is the presence of thrombus. Our laboratory has developed strategies to target thrombus using artificial platelets. Our platelets mimic the size, shape and flexibility of natural platelets and demonstrate remarkable ability to target the thrombus just like their natural counterparts. Our thrombus-targeting artificial platelets can be used to detect the presence of thrombus for diagnostic purposes as well as treat them by delivering thrombolytic agents. Our artificial platelets can also be potentially used as hemostatic agents to prevent severe blood loss during trauma and surgeries.
Pulmonary arterial hypertension (PAH) is a rare and chronic disorder of the pulmonary microvasculature, which is characterized by increased mean pulmonary arterial pressure (MPAP) of >25mm Hg at rest and >30mm Hg after exercise. PAH is a rare disease with 50,000-100,000 patients in the U.S. Current therapeutic regimen for PAH includes use of mostly injectable prostacyclin analogs including iloprost, and treprostinil; and certain oral endothelin receptor antagonists such as bosentan. However, the limitations of current therapy make it indispensable to use a continuous subcutaneous infusion and/or multiple administrations a day. At the same time, the non-selectivity of the current regimen is responsible for severe systemic hypotension and hepatotoxicity. In our laboratory, we are exploring novel approaches of lung targeting via cellular hitchhiking to treat pulmonary vasculature in PAH. Our targeted approach is expected to minimize the systemic side-effects and toxicity while reducing the dosing frequency, so as to utilize the currently approved regimen to its full therapeutic potential.
Psoriasis is a chronic and autoimmune skin disease. In the United States, about 7.5 million people suffer from psoriasis. Many treatments are available, but because of its chronic recurrent nature, psoriasis remains a challenge to treat. Typically topical agents are used for mild cases of psoriasis (affecting less than 3% of the body), phototherapy for moderate disease (affecting 3–10% of the body) and systemic agents for severe disease (affecting more than 10% of the body). Since 4 out of 5 patients suffering from psoriasis have the mild version, our lab primarily focuses on topical treatment. We have developed topical formulations to deliver cyclosporine into the skin for psoriasis treatment. We also develop formulation for the treatment of eczema, a condition that affects 5-20% of children worldwide. Here, we are developing topical formulations that deliver siRNA into the skin for knocking down key inflammatory proteins that are involved in manifestation of eczema.
Skin cancer is the most common class of malignancy in humans. In the United States, there are over 3 million cases of skin cancer a year. The vast majority of these skin cancers arise in keratinocytes, though melanoma accounts for the majority of skin cancer-related mortality. Worldwide, the incidence of skin cancers continues to rise. Inappropriate UV radiation is well established as the single most important environmental risk factor for skin cancers. Our laboratory is developing a non-invasive test to detect UV-induced DNA damage in the skin. This test will provide a means to detect skin cancer before its visual manifestation and serve as a method of screening patients to identify risk of developing skin cancer.
Preventable infectious diseases are responsible for about two third of deaths in children worldwide. Vaccines remain the primary tool in the fight against infectious disease. Most vaccines are given by needles and syringes. About 12 billion injections are given annually worldwide, most of which are related to vaccines. In spite of their common use, needles are limited by pain, discomfort and improper use. Every year millions of new infections of hepatitis and HIV are blamed on use of infected needles. Our laboratory is addressing this challenge by developing needle-free means of vaccination by using skin patches. Skin is a highly active immunesurveillant agent and delivery of vaccines into skin generates a robust systemic and mucosal immune response. Our laboratory is developing formulations to enhance delivery of vaccines into skin and simultaneously serve as adjuvants.
Acute and Chronic pain is one of the most prevalent health condition in the U.S. and worldwide. An estimated 50 million individuals suffer from chronic pain in the U.S. arising from various underlying causes including cancer and arthritis. Pain is the second leading cause of medically related causes of lost work leading to 50 million lost days each year. While excellent analgesic and anesthetic drugs exist to treat pain, many of them suffer from systemic toxicity, gastrointestinal damage and abuse. Our laboratory is addressing these challenges by developing novel drug delivery technologies focused primarily on topical delivery of medications at the site of pain, thus avoiding systemic and gastro-intestinal toxicity. These technologies include devices that include for example ultrasound and formulations to enhance penetration of pain analgesics into the skin. An ultrasound-based device for inducing local anesthesia has already been advanced to the clinic.