Drug delivery

Broad objective is to develop strategies to delivery drugs by different routes and approaches. Few projects are described below 

Delivery vehicles.  Many therapeutic molecules have short half-lives and one way to extend their life span is encapsulation.  Encapsulating regulatory factors and delivering them at a controlled rate provide opportunities: i) to create heterogeneous microenvironments within the matrix, unlike exogenous supplementation which creates a homogeneous microenvironment; ii) to continuously deliver regulatory factor, minimizing the time dependent variation in concentration, attributed to the frequency of the media change and half-lives of different growth factors; iii) to address the concerns related to incomplete secretion of growth factors into the cell culture medium in addition to the efficacy of genetically modified cellular components. Optimization of growth factor delivery and evaluation of cellular interactions in the matrices will help their usage in tissue healing.

Nanoparticle-based delivery.  Nanoparticles are employed in various therapeutic approaches for innovative drug delivery strategies. Various techniques exist to form nanoparticles from biodegrable polymers to liposomes with selective targeting.  We use double emulsion technique to form PLGA and PCL nanoparticles.  We form chitosan nanoparticles using tripolyphosphate (TPP) anions. Similar technology also exists to form gelatin nanoparticles. In addition, we form liposomes and derivatize with holo-transferrin and polyethylene glycol.   We use these particles in combination with various porous templates in tissue regeneration.

Microfiber-based delivery.  Alternative to nanoparticle-based encapsulation is to form drug-containing micro or nanofibers.  We work on using novel electrospinning technology to form various drug-containing fibers.  In order to control the release rate, we create co-axial and triaxial fibers from combinations of polymers that possess both required mechanical properties and biological properties.  One could use these mats of fibers along with hydrogels and create a heterogeneous environment.  Further, we can release various molecules selectively and sequentially for the differentiation of cells.

Transdermal drug delivery. Development of transdermal drugs requires the identification of suitable delivery mechanisms. Much effort has been directed towards the search for specific chemical or chemical combinations that could enhance drug penetration. However, effective chemical penetration enhancers (CPE) themselves permeate skin thereby eliciting some undesired reactions. Reliable and quantitative models for predicting precutaneous penetration and irritation as a function of chemical structure are required. The development of these models enables us to virtually screen for viable penetration enhancers thereby reducing the need for expensive experiments. The major goal of this project is to integrate non-linear, theory-based quantitative-structure-property-relationship (QSPR) modeling and robust genetic algorithms (GAs) to facilitate the design of improved CPEs. This is a collaborative project with Dr. Khaled Gasem at OSU.  Currently, a project assessing the transdermal delivery of insulin is pending in NIH.  If successful, this will have a significant impact on delivery systems.

Oral delivery.  In this cutting edge technology, pH-sensitive hydrogels are loaded with insulin and can be administered through the oral cavity. Unique feature of these hydrogels are that they form interpolymer complexes in an acidic environment and protect the insulin from the harsh stomach environment, a challenge to overcome for oral drug delivery. Insulin is safely released in the intestine due to the swelling of the carrier matrix at high pH and the delivery rate is influenced by particle size. Oral administration of insulin showed responses similar to subcutaneous delivery, suggesting the successful delivery of insulin orally.