Pharmacology Core Facility
This newly established core aims to provide consultation, services and trainings on validation, formulation, chemical analysis and characterization, nano-system delivery and pharmacokinetic studies of potential drug candidates that can treat or cause diseases that disproportionately impact minority health, especially cancer and cardiovascular diseases.
The projects at the Pharmacology Core will provide necessary data for internal investigators to apply for subsequent funding, to generate publications, to increase academic competitiveness of the investigators, and to improve biomedical research atmosphere at Texas Southern University. We aim to:
- Upgrade research infrastructure to enhance the university’s biomedical research in cancer and cardiovascular disease research which will help promote a research rich environment.
- Assist investigators in obtaining competitive extramural support to conduct biomedical research primarily in the areas of cardiovascular disease and cancer.
- Foster professional development in biomedical science research.
We will provide core’s user community with pharmacology-related services, including high-throughput drug screening, nanotech-based drug formulation and delivery, pre-formulation and formulation, mass spectrometry services and small animal studies. Internal investigators will be helped to build research capacity and provided networking opportunities.
Currently, we are also collaborating with many external researchers at major institutions and biotech companies, including UT-M.D. Anderson Cancer Center, UT at El Paso, National Cancer Institution, University of Houston, UT Health Science Center at Houston, Clark Atlanta University, Nanospectra Biosciences, Inc. etc. Several patents and publications have been generated and more are on the way. In summary, this Pharmacology Core is essential for the further development of biomedical research at TSU.
Available Services and Resources
Current available equipment: Titertek liquid handling system and Beckman Multimode plate reader for high-throughput screening; Labconco freeze dryer for lyophilizing drug formulation; Malvern Nano Zetasizer, Cytoviva imaging system and Varian UV-Vis spectrometer for formulation and characterization of nanodrug delivery systems; 3200 QTRAP LC-MS/MS, Thermo DSQ GC-MS for sensitive quantification analysis; and a small animal facility for preclinical and clinical pharmacokinetics and pharmacodynamics studies.
Nanotech-based Drug Formulation and Delivery component will initially focus on three aspects: nanodrug conjugation, in vitrodrug delivery and in vivodrug delivery. We will invest proposed RCMI funds in the acquisition of new instrumentation and material and supplies for existing infrastructure. For the nanodrug conjugation studies, the exiting equipment are Malvern Zetasizer Nano ZS, UV-Vis spectrometer, microplate reader, Cytoviva nano-imaging system, centrifuge, rotator, which are available at Gray Hall 216 in TSU campus. These instruments and equipment will be used to provide quantification and verification during each step of the conjugation process. We will provide consultation and research support on advanced nanoconjugation formulation for potential drug candidate and find the most stable and efficient formulation. We will also help to study the in vitro and in vivobinding affinity, efficiency and dosage. For the in vitrodrug delivery, cell culture and ELISA assays will be conducted in the Molecular Biology core facility. TSU also have a core facility will support the nanodrug research with high-resolution imaging (Scanning Electron Microscopy—SEM and Transmission Electron Microscopy—TEM)
Pre-formulation and Formulation can be performed with currently available instrumentation: liquid chromatography with mass spectrometry, ultra performance liquid choromatography, gas chromatograph-mass spectrometer, etc. Upon receiving a request from investigator, we will seek an analytical method that is capable of determining the molecule concentrations in different dosage forms as well as biological samples. A sensitive and specific high performance liquid chromatography (HPLC) assay will be developed. Different solvents will be used to find the proper formulation for the specific compound and their solubility and stability will be evaluated to get the best formulation for the compound’s application.
Mass Spectrometry Services will be offered to assist investigators with qualitative and quantitative measurement of small molecules. Typically these consist of drugs, metabolites, and related compounds. Specific small molecules of interest such as bioactive lipids and nutrients can also be easily measured. Services provided include the following: 1) Quantification of drugs and drug metabolites for pharmacokinetic analysis (LC-MS/MS); 2) Determination of drug metabolites; 3) Identification of complex unknown compounds (i.e., impurities, metabolites, small proteins); 4) Quantification of volatile drug and metabolites such as fatty acids, steroids (GC/MS). The currently available equipment are 3200 QTRAP LC-MS/MS for determination of mass weight of compounds and quantification of drugs and drug metabolites for pharmacokinetic analysis; thermo DSQ GC-MS instrument for identification of complex unknown compounds (i.e., impurities, metabolites, proteins), performance on unlimited fragmentation of compounds and quantification of volatile drugs and drug metabolites for pharmacokinetic analysis.
Small Animal Study: For the in vivo drug delivery and pharmacokinetics studies, the existing animal care facility (2,085 sq. ft.) located in Gray Hall is available to house and perform studies on mice and rats. In addition, screening experimental protocol services will be provided using zebrafish as a vertebrate animal model: zebrafish apoptosis assays for drug discovery, zebrafish angiogenesis bioassays, general toxicity, and specific toxicity.
High-Throughput Drug Screening component will have the following capabilities: (I) assay development and drug screening; (II) lead optimization; and (III) target identification and validation. We currently have DTX Beckman Coulter Multimode plate reader for spectrophotometric assays and a Titertek liquid handling system for high throughput drug screening compound libraries on specific drug targets as needed. We have procured two compound libraries from Sigma Aldrich which will be used in the initial drug screens. We also propose to purchase a third library from Chembridge in order to diversify our compound collection for drug screens. We are also affiliated with GCC-CG at the Texas Medical Center. We will obtain larger compound libraries from the GCC-CG. We will screen for potent and selective inhibitors using a high throughput drug screening approach with our liquid handling system. Once we identify “hits”, we will determine the IC50 of the most potent lead compounds, and then further determine their activity in cellular and toxicity assays. The compounds with the best pharmacological profiles will be further pursued in in vivo animal models. We will also validate the target using a chemical genetics approach by overexpression or knock down of the gene of interest.
Huan Xie, Ph.D.
Associate Professor of Pharmaceutical Sciences
Gray Hall 219
Yuan Chen, PhD
Jing Ma, MD