Rohan Research Group

Principal Investigator: Lisa Rohan, PhD

The focus of the Pharmaceutics Laboratory lies in the area of design of drug delivery and targeting systems. Several research topics are being pursued. The primary focus of the research in the lab is centered on the design of drug delivery systems for application in the areas of infectious disease and gynecologic oncology.

A major research program in the lab focuses on the development of microbicide products. HIV infection is a significant health problem worldwide with infection rates reaching pandemic levels. Heterosexual transmission has become a predominant route of infection for this disease. In heterosexually acquired cases of HIV, women are more susceptible to infection than men. Women account for nearly 50% of the people worldwide who are infected with HIV.

Microbicides are topical drug delivery systems that can be used to prevent transmission of sexually transmitted infections (STIs) including Human Immunodeficiency Virus (HIV). One important facet of such a product is that it would provide a female controlled method of prevention. There are approximately 19 million new cases of STIs reported in the US each year with nearly half of these infections being in youths between the ages of 15 and 24. UNAIDS predicts that an additional 45 million people will become infected with HIV by the year 2010 unless prevention efforts are achieved. Men and women urgently need infection prevention technology that is within their personal control. Microbicides would provide such a technology. The research in the Pharmaceutics lab focuses on the development of delivery systems for microbicide drug candidates including small molecules, natural products, peptides & proteins, as well as genetically altered bacteria. These systems range from traditional pharmaceutical products to novel vaginal drug delivery systems, which incorporate nanoparticulate technology or quick dissolve polymeric films. The lab currently collaborates to develop these microbicide products with groups around the world. In addition, the lab is currently studying the role of the chemical, physical, and biological properties of vaginal and cervical tissues and fluids in the development of vaginal and cervical products and developing in vitro model systems for use in the design of microbicide products. Other projects in the lab include the development and optimization of imaging techniques for sentinel node identification in cervical cancer as well as the development of novel delivery systems for chemotherapeutic agents.

Dr. Rohan is actively involved in several programs focused on the formulation of vaginal or rectal microbicide products for potential active agents encompassing small molecules including antiretrovirals, natural products, peptides and proteins, and genetically modified bacteria. In addition to her work in formulation development, Dr. Rohan’s research has also included establishing background data required for successful development of vaginal products.

This includes the evaluation of baseline activity of excipients on Lactobacillus, and STI’s including HIV, determination of permeability profiles for vaginal and cervical tissues, evaluation of toxicity of both formulated product and excipients, and rheological characterization of both marketed products and products developed in our laboratory for the delivery of pharmacologically active agents to the vagina. Prior to her academic career, Dr. Rohan was employed in the pharmaceutical industry. Her experience there covered all aspects of product development including preformulation, formulation development and assessment, scale up, and clinical studies. She has been working in the area of microbicide product development for the past 10 years. Her expertise lies in the design of drug delivery systems and the assessment of such systems with respect to safety, functionality, and efficacy.

Research Projects

The pharmaceutics laboratory at Magee is dedicated to identifying essential criteria for the design of drug delivery systems specific for women’s health issues. We are using this information to develop new products for women. Pharmaceutics involves the development of essential information that can be used to design drug delivery systems or dosage forms. Our focus is to get drugs to their target for action in a patient acceptable and safe manner while enhancing drug efficacy.

Drug delivery research in the pharmaceutics laboratory has been primarily focused in the areas of gynecologic oncology and infectious disease. A major focus of research in the lab has been toward the development of microbicide products.A microbicideis a chemical entity that can prevent or reduce transmission of sexually- transmitted infections when applied to the vagina or rectum.” Microbicide products would offer a female controlled method for prevention. HIV infection is a significant health problem worldwide with infection rates reaching pandemic levels. It has been shown that heterosexual transmission has become a predominant route of infection for this disease.

AIDS 2006 Video

In order to successfully design such drug delivery systems it is essential to have a full understanding of the female genital mucosa (vagina and ectocervix). Due to the anatomy and physiology of the female reproductive tract, women are twice as likely to become infected with the HIV/AIDS virus. It is estimated that women will account for 70-90% of new infections as a result of heterosexual intercourse. The Pharmaceutics Laboratory is conducting research in this area to better understand aspects which are needed for development of safe and effective vaginal products.

The Pharmaceutics Laboratory is currently working on a number of funded research projects in the area of microbicide product development. Several of these projects are listed below.

  • U19 AI065430 (PI Gupta P) NIH/NIAID “CV-N-secreting Lactobacilli and Retrocyclin Microbicides”

This program is centered on the development of a retrocyclin analog and genetically modified innate bacteria which secrete an antiHIV protein into separate safe and effective drug delivery systems.

  • U01 AI068633 (PI Hillier, SL)NIH/NIAID  “Microbicide Trials Network”

The mission of the MTN is to reduce the sexual transmission of HIV through the development and evaluation of products, which reduce the transmission of HIV when applied topically to mucosal surfaces. The goal is to conduct scientifically rigorous and ethically sound clinical trials of microbicide safety and effectiveness, which will support licensure of these products.

  • U19 AI060614 (PI Anton, P.) NIH/NIAID “Compartment-Specific Topical Microbicide Formulations”

The Pharmaceutics Lab is responsible for directing the pre-formulation, formulation development, and formulation assessment components of the project for rectal formulation of UC-781.

  • GMDC-08-04 (PI Rohan, L.) CONRAD/EVMS and Gates Foundation “Development of Quick Dissolve Film Drug Delivery Platforms for UC781, Tenofovir (TFV), and a Combination Product”

The aims of this study are 1) to develop a quick dissolve film dosage form for the delivery of UC781 as a single entity, 2) to develop quick dissolve film dosage forms for the delivery of tenofovir as a single entity, and 3) initiate development of a quick dissolve film dosage form for the combined delivery of UC781 and tenofovir.

  • GMDC-09-20 (PI Rohan, L.) CONRAD/EVMS and Gates Foundation “Evaluation of Permeability and HIV Efficacy in an Excised Human Tissue Model”

The following specific aims are being studied, 1) determine the release of UC781 and/or TFV from gel formulated products, 2) determine the permeability coefficient for UC781 and/or TFV through excised human cervical tissues when delivered in a gel dosage form, and 3) test the HIV-1 efficacy of UC781 and/or TFV formulated in a polarized human ectocervical tissue explant culture.

  • IPM  (PI Rohan, L.) International Partnership for Microbicide “Development of Vaginal Quick Dissolve Films Containing the Combinations of: Maraviroc/Tenofovir and Dapivirine/Maraviroc”

The primary objective of this project is to develop an R&D quality quick dissolve vaginal film dosage form containing a combination of maraviroc and tenofovir and a second product containing a combination of dapivirine and maraviroc.

  • 1 U19 AI082637  (PI McGowan, I.) NIH/NIAID “Combination HIV Antiretroviral Rectal Microbicide Program”

The specific aims of this project are: 1) to determine the potential protective effect of UC781 to prevent rectal HIV-1 infection; 2) to determine the efficacy of topically administered 9-R-2-phosphonylmethoxypropyl-adenine (PMPA) to prevent rectal HIV-1 transmission; and 3) to determine the protective effect of a combination of PMPA and UC781 to prevent rectal HIV-1 transmission.

  • RFA-AI-09-057 (PI Gupta, P.) NIH/NIAID  Formulation Core

The pharmaceutics lab is responsible for directing the pre-formulation, formulation development, and formulation assessment components of the project development of CSIC, RC-101, and the combination.

  • AI076169 (PI Palmer, K.) NIH/NIAID   “Antiviral Lectins as Microbicides”

Within the scope of this project is the proposed design of a formulation for delivery of Griffithsin (GRFT) to the vagina.

  • 1 U19 AI082639  (PIs Hillier, S & Rohan, L.) NIH/NIAID “Alternative Formulations of Tenofovir and UC781”

This project seeks to perform formulation research, preclinical and animal model testing and early (exploratory IND) clinical studies supporting development of film formulations of the nonnucleoside reverse transcriptase inhibitor (NNRTI), UC781 and the nucleoside reverse transcriptase inhibitor, tenofovir.

  • PATH (PI Rohan, L.) “Combining Microbicide Films and the Female Condom”

This study involves the preliminary study to evaluate the combination of microbicide loaded films with the PATH Women’s Condom. The goal is to increase the protective benefits of these two methods.

  •  Anonymous Donor (PI Rohan, L) “Development of a Film for HSV Prevention”

The aim of this project is to develop vaginal products that women can be used prior to sexual intercourse to prevent the transmission of herpes simplex virus (HSV).

Lab Members

Marilyn (Lyn) Cost, MS MBA

Senior Research Associate
Email

Philip Graebing, BS

Chemistry, Research Assistant
Email

Lin Wang, MS

Pharmaceutical Science, Research Assistant
Email

Ayman Akil, BS

Pharmacy - Graduate Student, School of Pharmacy, University of Pittsburgh
Email

Lindsay Ferguson

Pharm D Graduate Student, School of Pharmacy, University of Pittsburgh
Email

Tia Kimbro, BS

Chemistry - Graduate Student, School of Pharmacy, University of Pittsburgh
Email

Tian Tian Gong, BS

Visiting Scholar
Email

Michelle Chopra, BS

Chemical Engineering
Email

Lab Alumni - Visiting Scientists

2009

Christine Mesanga

Wageningen University, The Netherlands
University of Dar Es Salaam, Tanzania

2001                  

Alexandra B. Sassi

Uniao Quimica Farmaceutica Nacional, SP, Brazil

Lab Alumni - Residents

2006                                   

Amanda Nickles Fader, MD

Obstetrics & Gynecology Resident

Kathleen Moore MD

Obstetrics & Gynecology Resident

Lab Alumni - Postdoctoral Fellows

2008-present                 

Rama Mallipeddi, PhD

2007-2009                 

Mingguang Li, PhD

Current Position: Postdoctoral Fellow, Wayne State University

2007-2009                 

Anthony Ham, PhD

Current Position: Director of Formulation Sciences, ImQuest Pharmaceuticals

2004                                   

Tanuja Thakur, PhD

2003-04                   

Alexandra B. Sassi, Pharm D

Current Position: Principal Scientist, GlaxoSmithKline R&D

Medical Students

2006                                   

XiXi Wong

MD/PhD Candidate, University of Pittsburgh School of Medicine

1999                                     

Jodie Alton

University of Pittsburgh School of Medicine

Lab Alumni - Graduate Students

PhD Candidates

2008 - 2009

Gitanjali Sharma – University of Pittsburgh School of Pharmacy

2007                                    

Lilly Roy – University of Michigan School of Pharmacy
Jeremiah Momper – University of Pittsburgh School of Pharmacy
Mark Donnely – University of Pittsburgh School of Pharmacy

2006 - 2007                  

Claire Chen - University of Pittsburgh School of Pharmacy

2005- 2008                 

Alexandra B. Sassi – University of Pittsburgh School of Pharmacy
Current Position: Principal Scientist, GlaxoSmithKline R&D

2004 - 2005                 

Shringi Sharma - University of Pittsburgh School of Pharmacy

2003- 2009                 

Haitao Yang – University of Pittsburgh School of Pharmacy
Current Position – Senior Research Investigator; HIV and AIDS Program; Population Council

2000                                   

Deepali Vartak, PhD - Duquesne University School of Pharmacy

MS Candidates

2006 - 2007                                   

Megan Klamerus – Biology; Chatham College

PharmD Candidates

2008                                   

Michael Smith – University of Pittsburgh – START UP – CTSI Fellow

2007                                   

Lindsay Fergusan – University of Pittsburgh, CTSI Fellow
Yardlee Kaufmann – University of Pittsburgh

2005                                   

Katherine Francis – University of Pittsburgh
Toshiko L. Yamatani - University of Pittsburgh

2003                 

Nicole Whitehurst – Shenandoah University, VA – GEAR UP Program
Nicole Bruxvoort – Creighton University – GEAR UP Program

2002                                   

Babatunde Oyediran – Texas Southern University – GEAR UP Program

2001                                   

Carolyn Brisar – University of Pittsburgh

Undergraduate Students

2009                 

Aditee Shinde – University of Pittsburgh 
Jalal Aref – Pennsylvania State University

2008                 

Indrani Kar – University of Pittsburgh
Elina Mukherjee – University of Michigan

2006                 

Kelly Forney – University of Pittsburgh – GEAR UP Program

2005                 

Mahesh Madhavan – University of Pennsylvania

2004                 

Vanessa Haushalter – John Carroll University, Cleveland (Received Charles J. Stilwell Scholarship)
Courtney Adams – University of Pittsburgh

2002                 

Lyn Dudash – Georgia Tech

2001                                   

Meghan Roe – Notre Dame University

2000                                   

Kim Goldby-Reffner – Carlow College

High School Students

2006 & 2007                 

Matthew Swisher – Fox Chapel High School

2005                                   

Ang Li – Ellis School

2002 & 2003                 

Annie Gitomer – Ellis School

2002                                   

Jennifer Ng
Katie Horvath

2001                                   

Kira Dietz

2000                                   

Meghan Roe

1999                                   

Pradeep Vengetti
Kelly Van den Bosche

Selected Publications

  1. Rohan LC, Moncla BJ, Kunjara RP, Cost M, Huang Y, Gai F, BillottoN,  Lyman JD, Pryke K, Graebing P, Hopkins N, Rooney J,  Friend D, & Dezzutti CS.  In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide. PloS ONE, 5(2), Feb. 2010. e9310
  2. Ham AS, Cost M, Graebing P, Patton DL, Lederman M, Rohan LC. Targeted delivery of PSC-RANTES for HIV-1 prevention using biodegradable nanoparticles. Pharm Res, 26(3):502, 2009.
  3. Yang H, Parniak MA, Isaacs CE, Hillier SL, Rohan LC. Characterization of cyclodextrin inclusion complexes of the anti-HIV non-nucleoside reverse transcriptase inhibitor UC781. The AAPS J, 10(4):606, 2008.
  4. Mu Y, Klamerus M, Miller T, Rohan LC, Graham SH, & Poloyac SM. Intravenous Formulation of HET0016 for selective inhibition of rat brain 20-hydroxyeicosatetraenoic acid (20-HETE) formation. Drug Metabolism and Disposition, 36(11): 2324-30, Nov. 2008.
  5. Fader AN, Edwards RP, Cost M, Kanbour-Shakir A, Schwartz J, Kelley J, Comerci P, Sukumvanich P, Sumkin RP, & Rohan LC. Sentinel lymph node biopsy in early stage cervical cancer: Utility of intraoperative versus postoperative assessment. Gynecol Oncol, 111(1):13-7, Oct. 2008.
  6. Sassi AC, Isaacs B, Moncla B, Gupta P, Hillier SL, & Rohan LC. Effects of physiological fluids on physical chemical characteristics and activity of topical vaginal microbicide products. J Pharm Sci, 97(8):3123-39, Aug. 2008.
  7. Isaacs CE, Xu W, Jia JH, Rohan LC, Wen G, & Hillier SL. Epigallocatechin gallate inactivates clinical isolates of herpes simplex virus. Antimicrobial Agents and Chemotherapy, 52(3):962-70, 2008.
  8. Patton DL, Cosgrove SYT, Balkus JE, Rohan LC, Moncla BJ, Parniak MA, & Hillier SL. Preclinical  safety assessments of UC781 anti-HIV topical microbicide formulations. Antimicrobial Agents and Chemotherapy, 51:1608-15, 2007.
  9. Gupta PD, Dampf BK, Patterson, Rohan L, Parniak M, Isaacs CE, & Hillier SL. Use of frozen-thawed cervical tissues in the organ culture system to measure anti-HIV activities of candidate microbicides. AIDS Research & Human Retroviruses, 22(5):419-24, May 2006.
  10. Isaacs CE, Rohan LC, Xu W, Jia JH, Mietzner T, & Hillier SL. Inactivation of herpes simplex virus clinical isolates using a combination microbicide. Antimicrobial Agents and Chemotherapy, 1063-6, 2006.
  11. Poloyac SM, Rohan LC, Janjic JM, Gibbs RB, Kroboth PD, & Smith RB. GEAR-UP (Graduate Education And Research at the University of Pittsburgh): A program for educating students about pharmaceutical research. Amer J Pharm Educ, 69(5), 2005.
  12. Lampe ML, Rohan LC, Skinner MC, & Stamm WE. Susceptibility of chlamydia trachomatis to excipients commonly used in topical microbicide formulations. Antimicrobial Agents and Chemotherapy, 48(8): 3200-02, 2004.
  13. Sassi AB, McCullough KD, Cost MR, Hillier SL, & Rohan LC. Permeability of tritiated water through human cervical and vaginal tissue. J Pharm Sci, 93(8): 2009-16, 2004. Corresponding Author
  14. Rohan LC, Ratner D, McCullough K, Hillier SL, & Gupta P. Measurement of anti-HIV activity of marketed cream/gel vaginal products and excipients using a PBMC-based in vitro assay. Sexually Transmitted Diseases, 31(3):143-48, 2004.
  15. Olmsted SS, Meyn LA, Rohan LC, & Hillier SL. Glycosidase and proteinase activity of anaerobic gram-negative bacteria isolated from women with bacterial vaginosis. Sexually Transmitted Diseases, 30(3): 257-61, 2003.
  16. Rohan LC, Edwards RP, Kelly L, Colonello K, & Crowley-Nowick PA. Optimization of the wek-cel collection method for the quantification of cytokines in mucosal secretions. Clinical and Diagnostic Laboratory Immunology, 45-48, 2000.
  17. Black CA, Rohan LC, Cost M, Watkins S, Draviam R, Alber S, & Edwards RP. Induction of mucosal tolerance using vaginal suppositories in a mouse model. J Immunol, 165:5077-83, 2000.
  18. Rohan LC & Silvestri S. Effect of solvent system on microfluidization-induced mechanical degradation. Inter J Pharm, 95, 23-28, 1994.
Reviews, invited published papers, proceedings of conference and symposia, monographs, books and book chapters:
  1. Mallipeddi R & Rohan LC. Antiretroviral drug delivery using nanotechnology: Progress and perspective. Accepted for publication in Journal of Nanomedicine.
  2. Mallipeddi R & Rohan, LC. Nanoparticle based vaginal drug delivery systems for HIV prevention. Expert Opinionin Drug Delivery. 7(1):37-48, Jan. 2010.
  3. Rohan LC & Sassi AB. Vaginal drug delivery systems for HIV prevention. The AAPS Journal. 11(1):78, 2009.
  4. Romano J, Malcolm RK, Garg S, Rohan LC, & Kaptur PE. Microbicide delivery: Formulation technologies and strategies. Current Opinion in HIV and AIDS, 3:558-66, 2008.
  5. Pickett J, LeBlanc MA, Anton P, Carballo-Dieguez A, Gorbach P, Harrison P, Hendrix C, McCormack S, McGowan I, Phillips D, & Rohan L. Less silence, more science: Advocacy to make rectal microbicides a reality. Released at the 2008 Microbicides Conference, Capetown, South Africa. Available IRMA Report online (International Rectal Microbicides Advocates).
  6. Rohan LC, Hillier SL, & Dezzutti CS. Preventing the sexual transmission of HIV-1 with topical microbicides: Another piece of the equation. J Infec Dis, 196:1285-7, 2007.
  7. Schnaare RL, Block LH, & Rohan LC. Rheology. In Remington: The science and practice of pharmacy, 21st edition, Popovich, N (eds); Advanced Concepts Institute, University of the Sciences in Philadelphia, Philadelphia, PA. pp. 338-357, 2005.

Services & Protocols

The pharmaceutics laboratory has an open IRB protocol for the collection of vaginal fluids from women (IRB number PRO07050142). This study provides essential biological fluids to assist in the design of safe and effective vaginal products for women.

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