University Directory

Clyde M. Ofner III, PhD

Professor

Clyde M. Ofner III PhD

Department

Office

Robert McNeil Graduate Study and Research Center 109B

Phone

215-596-8881
Contact

Clyde M. Ofner III, PhD, RPh joined the Philadelphia College of Pharmacy (PCP) in 1987. He is a professor in the department of pharmaceutical sciences. His responsibilities include teaching courses in programs of Pharmacy, Pharmaceutical Sciences, Pharmacology/Toxicology, and the graduate Pharmaceutics, and Drug Development and Industrial Pharmacy (DDIP) programs. Research in his group has two themes. The first is macromolecular anti-cancer conjugates for breast cancer therapy. The second theme is intracellular lysosomes for anti-cancer research. See the section on Research for more information about his research. 

Dr. Ofner has directed the research of over a dozen graduate students and several dozen undergraduate students. He has over a hundred publications of research articles, research abstracts, and book chapters. His research has been funded by the NIH, several national and regional foundations, awards from SJU, PCP, and several pharmaceutical companies. He and his students have received over a dozen research fellowships for graduate and undergraduate students. Dr. Ofner received the FDA Commissioner’s Special Citation for his work on the Gelatin Capsule working group of the FDA (1995-1998). He served on NIH SBIR/STTR study sections for review of grants (2009, 2012). He received the USciences Founders Day Faculty Award of Merit (2016). He received the PCP Dean’s Award in Research (2013), in Teaching (2020), and in Service (2023). He and his students have patents on a high molecular weight biodegradable gelatin-doxorubicin conjugate in the US, Europe, Canada. 

Dr. Ofner is a licensed pharmacist in the state of Pennsylvania, and is the faculty advisor to the student chapter of the honor society of pharmacy (Rho Chi), a member of the American Association for Pharmaceutical Scientists (AAPS), and the American Association for Cancer Research (AACR).

    • BS, Temple University
    • PhD, Temple University

  • R.E. Nicoletto and C.M. Ofner III, “Lysosome-mediated cytotoxicity in breast cancer subtype cells treated with doxorubicin.” submitted, J. Pharm Pharmacology
     
    R.E. Nicoletto and C.M. Ofner III, “Cytotoxic mechanisms of doxorubicin at clinically relevant concentrations in breast cancer cells”. Cancer Chemotherapy and Pharmacology, 89:285-311 (2022). https://doi.org/10.1007/s00280-022-04400-y
     
    M.M. Alvi, R.E. Nicoletto, B.A. Eshmawi, H.K. Kim, C.R. Cammarata, C.M. Ofner III, “Intracellular trafficking and cytotoxicity of a gelatin-doxorubicin conjugate in two breast cancer cell lines.” J. Drug Target., 28(5):487-499 (2020). DOI:10.1080/1061186X.2019.1679820
     
    C.R. Cammarata, M.E. Hughes and C.M. Ofner III, “Carbodiimide Induced Crosslinking, Ligand Addition, and Degradation in Gelatin.” Mol. Pharmaceutics, 12:783-793 (2015).
     
    D.C. Wu, C.R. Cammarata, H.J. Park, B. Rhodes, C.M. Ofner III, “Preparation, Drug Release, and Cell Growth Inhibition of a Gelatin Doxorubicin Conjugate.” Pharm. Res, 30(8):2087-2096 (2013). DOI: 10.1007/s11095-013-1065-9.
     
    D.C. Wu and C.M. Ofner III, “Adsorption and Degradation of Doxorubicin from Aqueous Solution in Polypropylene Containers.” AAPS PharmSciTech, 14(1):74-77 (2012). DOI: 10.1208/s12249-012-9885-1.
     
    B. Shank and C.M. Ofner III, “Multi-Temperature Stabililty and Degradation Characteristics of Pergolide Mesylate Oral Liquid.” J. Pharm. Pract, 23(6):570-574 (2010).
     
    B. Shank and C.M. Ofner III, “Determination of the Stability of Pergolide Mesylate Oral Liquid at Room Temperature.” Int. J. Pharm. Comp., 13(3):254-258 (2009).

    • C.S. Chen and C.M. Ofner III. "The Effect of Charge, Drug Load, and Molecular Weight of Gelatin-Methotrexate Conjugates on Cytoxicity in HL60 Leukemia Cells." Pharm. Res., 26:338-345 (2009).
    • D.C. Wu, G. Williams, M. Tasheva, B. Rhodes, C.M. Ofner III. "Preliminary Evaluation of pH Controlled Drug Release from a Gelatin – Doxorubicin Conjugate." The AAPS Journal, 11(S2): Abstract #T3409, 2009.
    • C.M. Ofner III, C.S. Chen, K. Pica. "Macromolecular Conjugates for Passive Tumor Targeting: In Vitro Studies with a Gelatin-Methotrexate Conjugate." EHRLICH II-2nd World Conference on Magic Bullets, Nurnberg, Germany, October 4, 2008.
    • R. Desai, N. Patel, C.S. Chen, C.M. Ofner III. "Cytostatic and Cytocidal Effects of a Gelatin-Methothrexate Conjugate and Free Methotraxate on HL60 Leukemia Cells." The AAPS Journal, 9(S2): Abstract T3366 (2007).
    • C.M. Ofner III. "Soluble Macromolecular Conjugates for Passive Tumor Targeting." Philadelphia Pharmaceutical Forum, North Wales, P.A., January 11, 2007
    • C.M. Ofner III, K. Pica, B.J. Bowman, C.S Chen. "Growth Inhibition, Degradation, and Methotrexate Release Studies of Gelatin/Methotrexate Conjugates." Int.J.Pharm., 308: 90-99 (2006)
    • J.W. Mwangi and CM Ofner III. "Crosslinked Gelatin Matrices: Release of a Random Coil Macromolecular Solute." Int. J. Pharm. 278:319-327 (2004)
    • C.M. Ofner III, Y.E. Zhang, V.C. Jobeck, B.J. Bowman. "Crosslinking Studies in Gelatin Capsules Treated with Formaldehyde and in Capsules Exposed to Elevated Temperature and Humidity." J. Pharm. Sci., 90(1):79-87 (2001).

  • Our research began with a chemistry focus in drug delivery. While it has shifted to a cellular focus, we have continued an interest in drug delivery. We published results of a macromolecular methotrexate conjugate in HL60 leukemia cells in 2009. Next, we published results of a macromolecular doxorubicin (DOX) conjugate in EL4 mouse lymphoma and PC3 human prostate cells in 2013. Following that, we published results of a second macromolecular DOX conjugate in breast cancer cells in 2019. Currently, we are investigating a macromolecular paclitaxel complex in breast cancer cells. 
     
    Within our cellular focus, we are investigating intracellular lysosomes for anti-cancer research. Lysosome membrane permeabilization (LMP) induces translocation of active lysosomal enzymes to the cytoplasm which can produce apoptotic cell death or more broadly, lysosome dependent cell death (LDCD). This cell death pathway has received attention to potentially treat cancer because it may evade the well-known toxic side effects with current chemotherapy. In addition, cancer lysosomes may be more fragile than lysosomes in normal cells which raises the possibility of only inducing LMP in cancer cells without harm to non-cancerous cells and tissues. Our first lysosome investigation involved the second DOX conjugate noted above and it induced substantial LMP and cytotoxicity in triple negative breast cancer (TNBC) cells.
     
    In a recent investigation with lysosomes, we found a previously unidentified LMP from free DOX (unconjugated) that induced cytotoxicity in breast cancer cells and that it involved reactive oxygen species (ROS) and p53 pathways. Interestingly, we found greater DOX induced LMP and apoptosis in wild type p53 compared to mutant p53 breast cancer cells. We are also investigating a novel fluorescent methodology to evaluate lysosome swelling as a precursor to LMP. These results have led us to investigate a potential anti-cancer approach with LMP and LDCD in wild type p53 breast cancer cells. This approach has the potential to selectively treat breast cancer cells without harm to healthy tissue which is a highly desirable outcome