Education:

B.Pharm., 1997
The Tamil Nadu Dr. M.G.R. Medical University, India

M.Pharm. in Pharmaceutics, 1999
Banaras Hindu University, India

Ph.D. in Pharmaceutical Sciences, 2003
University of Nebraska Medical Center

Research Interests:

TUMOR DRUG RESISTANCE.  Despite advances in diagnostic techniques and discovery of potent anticancer agents, cancer remains the second leading cause of death in the United States.  Development of resistance to multiple drugs is a major hurdle to the success of anticancer therapies.  Current treatment approaches are not successful in overcoming the multifactorial nature of tumor drug resistance.  We are currently investigating two different approaches to overcome drug resistance:

• Dual gene silencing and drug delivery.  Overexpression of specific cellular proteins such as drug transporters, drug metabolizing enzymes, anti-apoptotic factors or other cellular proteins results in the development of drug resistance.  Inhibition or a reduction in the expression of these proteins in tumor cells could increase the sensitivity of resistant tumor cells to chemotherapeutic agents such as paclitaxel.  In this project, we are investigating dual gene silencing and drug delivery using nanoparticles to overcome drug resistance.  Two cellular proteins (P-glycoprotein and Heat shock protein 70) that contribute to the development of drug resistance will be targeted for gene silencing.  Gene silencing will be achieved using short interfering RNA (siRNA)-mediated RNA interference.  The central hypothesis of the proposed research is that dual-agent nanoparticles will sustain the cellular delivery of siRNA and paclitaxel, resulting in enhanced paclitaxel accumulation and cytotoxicity, and ultimately, regression of resistant tumor.  Nanoparticles formulated using the biocompatible polymer poly(D,L-lactide-co-glycolide) are used to deliver both paclitaxel and P-gp or Hsp70– targeted siRNA to resistant tumor cells.
• Combination photodynamic therapy and chemotherapy.  The objective of this project is to demonstrate the effectiveness of nanotechnology-mediated combination photodynamic therapy (PDT) and chemotherapy against drug-resistant cancer. Nanoparticles formulated using a biocompatible surfactant Aerosol OT (AOT) and a polysaccharide polymer alginate will be used for tumor-targeted delivery of the combination therapy. The hypothesis of the proposed research is that nanoparticle-mediated simultaneous PDT and chemotherapy will target multiple mechanisms of tumor drug resistance, resulting in effective inhibition of resistant tumor.  Enhanced accumulation of anticancer drug at the site of action, additive cytotoxicity, inhibition of drug efflux, release of sequestered drug from acidic endosomes, vascular shutdown, induction of anti-tumor immunity are the expected benefits of the proposed combination approach. Initial studies with doxorubicin as a model anticancer drug and methylene blue as a model photosensitizer demonstrate that nanoparticle-mediated combination therapy effectively overcomes drug resistance in vitro and in vivo. We believe that this approach has the potential to trigger the immune system to destroy not only the primary tumor but also distant micrometastases.

TARGETING CHLAMYDIAL INFECTIONS.  Human infections by the intracellular bacterial pathogens Chlamydia trachomatis and C. pneumoniae present an enormous health care problem.  The former is the most prevalent sexually transmitted bacterium and is associated with blinding trachoma, while C. pneumoniae is a respiratory pathogen responsible for a significant proportion of community-acquired pneumonia.  Both pathogens often enter an unusual biologic state designated “persistence”, and in this form have been associated with engendering several chronic diseases.  Persistent infections by both organisms have proved to be refractory to antibiotic therapy.  The lack of therapeutic efficacy results from the attenuated metabolic rate of persistently infecting chlamydiae in combination with the modest intracellular concentrations achievable by normal delivery of such drugs to the inclusions within which chlamydiae reside in the host cell cytoplasm.  A major therapeutic goal of this research is to develop a means by which antibiotics or other therapeutic agents can be delivered in a targeted manner to the intracellular chlamydial inclusion at effective concentrations without toxicity to the host cell or infected tissue.  Our initial studies indicate that chlamydial infection elicits increased expression of specific host cell receptors, and targeting these receptors may provide a novel and highly effective means of intracellular delivery of therapeutic agents to Chlamydia-infected cells.  We are currently pursuing studies in mice to determine if delivery of antibiotics to Chlamydia-infected mice using targeted nanoparticles clears persistent synovial infection in vivo. If successful, results of this research will suggest a novel nanotechnology-based therapeutic regimen for effective treatment of an important health care problem. (Co-Investigators: Dr. Judith Whittum-Hudson and Dr. Alan P. Hudson, Wayne State University)

Selected Publications:

Chavanpatil M., Khdair A., and Panyam J. (2006) Nanoparticles for cellular drug delivery: mechanisms and factors influencing delivery.  J. Nanosci. Nanotech. 6: 2651-63.

Chavanpatil M., Patil Y., and Panyam J. (2006) Susceptibility of nanoparticle-encapsulated paclitaxel to P-glycoprotein-mediated drug efflux.  Int. J. Pharm. 320: 150-156.

Chavanpatil M., Khdair A., Patil Y., and Panyam J. (2007) Surfactant-polymer nanoparticles: A novel platform for sustained and enhanced cellular delivery of water-soluble molecules.  Pharm. Res. 24: 803-10.

Chavanpatil M., Handa H., Mao G., and Panyam J. (2007) Incorporation of phospholipids enhances cellular uptake and retention of surfactant-polymer nanoparticles.  J. Biomed. Nanotech. (in press).

Chavanpatil M., Khdair A., Patil Y., Handa H., Mao G., and Panyam J. (2007) Polymer-surfactant nanoparticles for sustained release of water-soluble drugs.  J. Pharm. Sci. (PubMed).

Chavanpatil M., Khdair A., Gerard B., Bachmeier C., Shekar M., Miller D.W., and Panyam J. (2007) Surfactant-polymer nanoparticles overcome P-glycoprotein-mediated drug efflux.  Mol. Pharm. (PubMed).

Shahani K., Jonnalagadda K., Handa H., Mao G. and Panyam J. (2007) Phospholipid nanoparticles: process optimization using factorial design and atomic force microscopy. (communicated)