Assistant Professor, Physiological Sciences
Research Focus: Image Guided Drug Delivery
Cancer chemotherapy employs systemic delivery of antitumor drugs with limited specificity, causing toxic side effects in normal tissues and inefficient/insufficient drug delivery to tumor cells that leads to recurrence. To address these problems, liposomal stealth drug delivery systems (e.g. Doxil) have been developed to selectively accumulate tumors, permitting enhanced intratumoral drug delivery while reducing drug exposure and toxicity to normal tissue. However, available clinically-approved nanocarriers release their payload only within the perivascular space of tumors, impeding or preventing distribution to poorly-perfused remote cells in the tumor core that contribute to drug resistance and tumor recurrence. Thus the tumor-directed dose escalations achieved to date via stealth liposome technology have not yet improved treatment efficacy. To overcome these limitations, the long-term goal of our laboratory is to optimize and provide uniform intratumoral delivery of antitumor drugs with real-time control, thereby providing clinical more precise dosing control. Ongoing projects are focused on development of drug encapsulated thermosensitive nanocarriers that can achieve homogeneous, tightly-controlled intratumoral delivery of antineoplastic drugs. Parallel efforts are centered on utilizing thermoregulatory-mediated elevations of blood flow in vascular beds proximal and distal to the tumor vasculature under image guidance that may improve blood flow through the tumor, perhaps in part by drawing excess fluid from tumor stroma and thereby relieving interstitial pressure, and decompressing tumor vasculature.
Selected peer-reviewed publications
- Partanen A., Yarmolenko P.S., Viitala A., Appanaboyina S., Haemmerich D.,Enholm J., Ranjan A., Jacobs G., Woods D., Wood B.J., Dreher M.R, Mild hyperthermia with magnetic resonance guided high-intensity focused ultrasound for drug delivery, Int J Hyperthermia. 2012;28(4):320-36
- Ranjan, A. Pothayee N., Seleem M., Boyle SM., Kasimanickam R, Riffle J. S., Sriranganathan N. Nanomedicine for Intracellular therapy, FEMS Microbiol Lett. 2012 Jul;332(1):1-9
- Ranjan A, Jacobs GC, Woods DL, Negussie AH, Partanen A, Yarmolenko PS, Gacchina CE, Sharma KV, Frenkel V, Wood BJ, Dreher MR, Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model, J Control Release. 2012 Mar 28;158 (3):487-94
- Negussie A.H., Yarmolenko P.S., Partanen A., Ranjan A., Bryant H., Thomasson D., Dewhirst M.W., Dreher M.R., Wood B.J. Formulation and characterization of Magnetic Resonance Image-able thermally sensitive liposomes for use with magnetic resonance guided high intensity focused ultrasound, International Journal of Hyperthermia, 2011; 27(2):140-55. (Cover Page)
- Ranjan, A., Seleem M.N., Pothayee N., Restis E., Sriranganathan N., Riffle J. S., Kasimanickam R. Efficacy of amphiphilic core-shell nanostructures encapsulating gentamicin in an in-vitro Salmonella and Listeria intracellular infection model , Antimicrobial Agent & Chemotherapy. 2010; Aug; 54(8):3524-6.
- Ranjan A., Seleem M., Jain N., Pothayee N., Sriranganathan N., Riffle J. S., Kasimanickam R., Drug delivery using novel nanoplexes against a Salmonella mouse infection model, Journal of Nanoparticle Research. 2010; 12:905–914
- Ranjan, A., Seleem M., Jain N., Pothayee N., Sriranganathan N., Riffle J. S., Kasimanickam R., In-vitro trafficking and efficacy of core-shell nanostructures fortreating intracellular Salmonellosis, Antimicrobial Agents and Chemotherapy.2009; Vol.53 (9); 3985-3988
- Ranjan A., Seleem M., Pothayee N., Tyler Jr R., Brenseke B., Sriranganathan N., J. S. Riffle, R. Kasimanickam. Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in-vivo intracellular Salmonella model, International Journal of Nanomedicine. 2009; Vol.4:289-97
- Seleem M., Munusamy P., Ranjan A., Alqublan H., Pickrell G., Sriranganathan N. Silica-antibiotic hybrid nanoparticles for targeting intracellular pathogens. Antimicrobial Agent and Chemotherapy, 2009; Vol. 53(10): 4270-4274
- Seleem M., Jain N., Pothayee N., Ranjan A., Sriranganathan N., Riffle J. S. Streptomycin-Doxycycline nanoparticles for targeting Brucella melitensis infection. FEMS Microbiology Letters. 2009; Vol.294:24-31
- Pothayee, N., Vadala M., Ranjan A., Jain N., Seleem M., Sriranganathan N., Riffle J.S. Aminoglycoside-ionopolymeric nanoplexes for treating intracellular bacterial pathogens. Abstracts of papers of the American Chemical Volume. 2008; Vol.236:237
- Pothayee N., Vadala M. L., Ranjan A., Jain N., Seleem M., Sriranganathan N, Riffle J.S. Aminoglycoside-ionopolymeric nanoplexes for treating intracellular pathogens intracellular pathogens, Polymer Preprints 2008; Vol. 49:1037