Our research addresses two major challenges in achieving enhanced and modulated drug delivery:

       One major challenge in oral drug delivery has been the low bioavailability of many crystalline compounds exhibiting poor solubility characteristics. This challenge becomes more significant for controlled release delivery of such drugs where a combination of solubility enhancement and release modulation of the drug is required. Our research in this area is focused on the formation, characterization, and drug delivery applications of nanostructured drug-polymer composites. On one hand, we are interested in understanding the nucleation and crystallization kinetics in drug loaded hydrogels in both the swollen (rubbery) and dehydrated (glassy) states, as well as their effects on subsequent dissolution and release of the drug from such polymeric carriers. On the other hand, we are investigating physicochemical parameters that effectively retard such crystallization process in the solid state such that a stable solid solution or amorphous drug-polymer composite can be created in glassy hydrophilic polymer carriers. Such stabilized amorphous drug-polymer composites would increase and prolong the transient kinetic solubility and provide enhanced bioavailability of poorly soluble drugs. As a result, we are also elucidating the effect of rate of supersaturation generation on the evolution of such kinetic solubility profile during the dissolution of amorphous drug under non-sink finite volume conditions similar to that encountered in the GI tract. Additionally, we are interested in modulating the release of poorly soluble drugs from such nanostructured drug-polymer composites through direct modification of the spatial distribution of either the drug or the polymer structure

       Another major challenge is related to enhanced and modulated delivery of nitric oxide (NO). NO is a critical mediator for tissue repair. Studies have linked impaired wound healing in diabetic ulcer patients to NO deficiency at the wound site. Topical administration of NO or NO donors appears to be beneficial in promoting tissue repair and healing of diabetic ulcers in animal models. However, this mode of treatment is limited by the short duration of NO release, short half-life of NO in physiological fluid, and the intrinsic instability of available NO donors. Currently, clinical materials that can achieve prolonged release of NO at the wound site are still lacking. To overcome these deficiencies, we have developed a novel nitric oxide delivery system based on a new class of biocompatible supramacromolecular complexes potentially useful for treating chronic non-healing wounds such as diabetic ulcers. This system provides a controlled release NO for an extended duration of over 10 days generally not achievable by existing systems, and shows accelerated wound closure in a diabetic animal model from a single application. All components of the proposed NO delivery system have prior history of use in man and in approved drug products, thus potentially can avoid extensive toxicology studies & shortening time to the clinical testing. We are interested in demonstrating enhanced wound healing properties through histology assessment and gaining in-depth understanding of mechanisms of NO release and physicochemical parameters influencing the design of such NO delivery system.

Publications

 PIL Research Group 2014. Designed by Zheng Li.

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