You are here:

Hamid Ghandehari

Professor of Pharmaceutics and Pharmaceutical Chemistry
and Professor of Bioengineering

Ghandehari Photo

B.S. University of Utah

Ph.D. University of Utah

Research

References

hamid.ghandehari@pharm.utah.edu

Hamid Ghandehari's Lab Page

Hamid Ghandehari's PubMed Literature Search

Biological Chemistry Program

Nanomedicine and Drug Delivery

Research

The main focus of research in our laboratory is the development of novel methods for controlled delivery of bioactive agents. Four areas are being explored:

1. Genetically engineered polymers for gene delivery
Recombinant DNA technology has enabled the synthesis of protein-based polymers with precisely controlled structures. Control over polymer structure at the molecular level has important implications for controlled delivery applications. The potential of recombinant silk-elastinlike protein polymers (SELPs) for matrix-mediated gene delivery is being explored. The idea is that by using recombinant techniques it is possible to systematically correlate polymer structure with gene release and transfer. Our main focus is on gene therapy applications in the treatment of head and neck cancer. For a recent article see [J.Gustafson, H. Ghandehari, Advanced Drug Delivery Reviews,  62:1509-1523, 2010]. More recent efforts focus on design of recombinant polymers with sequences responsive to matrix-metalloproteinases [J. Gustafson, R. Price, J. Frandsen, C.R. Henak, J. Cappello, and H. Ghandehari, Biomacromolecules, 14:618-625, 2013].

2. Water-soluble polymers for targeted delivery
Targeted delivery of bioactive agents by water soluble polymers can increase efficacy and reduce toxicity. The synthesis, characterization and biological evaluation of targetable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers for targeted delivery to angiogenic blood vessels of solid tumors have been investigated [D. Pike, H. Ghandehari, Advanced Drug Delivery Reviews, 62:167-183, 2010]. More recent efforts focus on gold nanorod-mediated hyperthermia for enhanced delivery of macromolecular therapeutics to solid tumors [A.J. Gormley, N. Larson, S. Sadekar, R. Roinson, A. Ray, and H. Ghandehari, Nano Today, 7:158-167, 2012; N. Larson, A. Gormley, N. Frazier, and H. Ghandehari, Journal of Controlled Release, 170:41-50, 2013].

3. Poly(amidoamine) dendrimers for oral delivery
Due to their large size water soluble polymers generally need to be administered intravenously. It would be desirable to develop polymeric carriers that are orally bioavailable. Nano-scale poly(amidoamine) (PAMAM) dendrimers of appropriate size, charge and concentration can be transported across the gastrointestinal epithelial cells with minimal or no toxicity. The influence of variables such as size, charge, surface functionality and drug loading on the mechanism and rate of transport of PAMAM dendrimers across epithelial  barriers has been investigated. More recent efforts focus onin vivo oral bioavailability of PAMAM dendrimers and their transepithelial transport across isolated intestinal tissue.  For a recent article on this topic see [S. Sadekar and H. Ghandehari, Advanced Drug Delivery Reviews, 64:571-88, 2012].

4. Nanotoxicology of dendritic and inorganic constructs
Recent advances in nanotechnology have enabled the fabrication of inorganic nanoconstructs with defined shape, size, and surface functionality. Examples of such constructs include inorganic nanorods and nanospheres. Efforts are directed at evaluating the influence of geometry and surface functionality on biocompatibility and biodistribution of silica and gold nanoparticles, as well as poly(amido amine) dendrimers. For recent articles see [K. Greish, G. Thiagarajan, H. Herd, R. Price, H. Bauer, D. Hubbard, A. Burckle, S. Sadekar, T. Yu, A. Anwar, A. Ray, and H. Ghandehari, Nanotoxicology, 6:713-723, 2012; T. Yu, K. Greish, L. McGill, A. Ray, and H. Ghandehari, ACS Nano, 6:2289-2301, 2012; H. Herd, N. Daum, A. Jones, H. Huwer, H. Ghandehari, and C.M. Lehr, ACS Nano, 7:1961-1973, 2013].

References

  1. Price R, Poursaid A, Cappello J, Ghandehari H (2015) In vivo evaluation of matrix metalloproteinase responsive silk-elastinlike protein polymers for cancer gene therapy. Journal of Controlled Release, Jun 18. pii: S0168-3659(15)00629-X. doi: 10.1016/j.jconrel.2015.06.022. [Epub ahead of print]
  2. Frazier N, Ghandehari H. (2015) Hyperthermia approaches for enhanced delivery of nanomedicines to solid tumors. Biotechnology and Bioengineering, May 20. doi: 10.1002/bit.25653. [Epub ahead of print]
  3. Poursaid A, Price R, Tiede A, Olson E, Huo E, McGill L, Ghandehari H, Cappello J (2015) In situ gelling silk-elastinlike protein polymer for transarterial chemoembolization. Biomaterials, 57:142-52
  4. Herd HL, Bartlett KT, Gustafson JA, McGill LD, Ghandehari H (2015) Macrophage silica nanoparticle response is phenotypically dependent. Biomaterials, 53:574-82
  5. Jung SH, Choi JW, Yun CO, Kim SH, Kwon IC, Ghandehari H (2015) Direct observation of interactions of silk-elastinlike protein polymer with adenoviruses and elastase.  Molecular Pharmaceutics, 12(5):1673-9
  6. Frazier N, Robinson R, Ray A, Ghandehari H (2015) Effects of heating temperature and duration by gold nanorod mediated plasmonic photothermal therapy on copolymer accumulation in tumor tissue. Molecular Pharmaceutics, 12(5):1605-14
  7. Larson N, Roberts S, Ray A, Buckway B, Cheney DL, Ghandehari H (2014) In vitro synergistic action of geldanamycin- and docetaxel-containing HPMA copolymer-RGDfK conjugates against ovarian cancer. Macromolecular Bioscience, 14(12):1735-47
  8. Price R, Poursaid A, Cappello J, Ghandehari H (2014) Effect of shear on physicochemical properties of matrix metalloproteinase responsive silk-elastinlike hydrogels. Journal of Controlled Release, 195:92-8
  9. Hubbard D, Ghandehari H, Brayden DJ (2014) Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers. Biomacromolecules, 15(8):2889-95
  10. Jung SH, Choi JW, Yun CO, Yhee JY, Price R, Kim SH, Kwon IC, Ghandehari H (2014) Sustained local delivery of oncolytic short hairpin RNA adenoviruses for treatment of head and neck cancer. Journal of Gene Medicine, 16(5-6):143-52
  11. Price R, Poursaid A, Ghandehari H (2014) Controlled release from recombinant polymers. Review. Journal of Controlled Release, 190:304-13
  12. Astashkina AI, Jones CF, Thiagarajan G, Kurtzeborn K, Ghandehari H, Brooks BD, Grainger DW (2014) Nanoparticle toxicity assessment using an in vitro 3-D kidney organoid culture model. Biomaterials, 35(24):6323-31
  13. Buckway B, Frazier N, Gormley AJ, Ray A, Ghandehari H (2014) Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer-90Y conjugates in treatment of prostate tumors. Nuclear Medicine and Biology, 41(3):282-9
  14. Buckway B, Wang Y, Ray A, Ghandehari H (2014) In vitro evaluation of HPMA-copolymers targeted to HER2 expressing pancreatic tumor cells for image guided drug delivery. Macromolecular Bioscience, 14(1):92-9
  15. Varongchayakul N, Johnson S, Quabili T, Cappello J, Ghandehari H, Solares Sde J, Hwang W, Seog J (2013) Direct observation of amyloid nucleation under nanomechanical stretching. American Chemical Society Nano, 7(9):7734-43
  16. Buckway B, Wang Y, Ray A, Ghandehari H (2013) Overcoming the stromal barrier for targeted delivery of HPMA copolymers to pancreatic tumors. International Journal of Pharmaceutics, 456(1):202-11
  17. Sadekar S, Thiagarajan G, Bartlett K, Hubbard D, Ray A, McGill LD, Ghandehari H (2013) Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin. International Journal of Pharmaceutics, 456(1):175-85
  18. Larson N, Yang J, Ray A, Cheney DL, Ghandehari H, Kopeček J (2013) Biodegradable multiblock poly(N-2-hydroxypropyl)methacrylamide gemcitabine and paclitaxel conjugates for ovarian cancer cell combination treatment. International Journal of Pharmaceutics, 454(1):435-43
  19. Moos PJ, Honeggar M, Malugin A, Herd H, Thiagarajan G, Ghandehari H (2013) Transcriptional responses of human aortic endothelial cells to nanoconstructs used in biomedical applications. Molecular Pharmacology, 10(8):3242-52
  20. Sadekar S, Linares O, Noh G, Hubbard D, Ray A, Janát-Amsbury M, Peterson CM, Facelli J, Ghandehari H (2013) COMPARATIVE PHARMACOKINETICS OF PAMAM-OH DENDRIMERS AND HPMA COPOLYMERS IN OVARIAN-TUMOR-BEARING MICE. Drug Deliv Transl Res, 3(3):260-271
  21. Larson N, Gormley A, Frazier N, Ghandehari H (2013) Synergistic enhancement of cancer therapy using a combination of heat shock protein targeted HPMA copolymer-drug conjugates and gold nanorod induced hyperthermia. Journal of Controlled Release, 170(1):41-50
  22. Thiagarajan G, Greish K, Ghandehari H (2013) Charge affects the oral toxicity of poly(amidoamine) dendrimers. European Journal of Pharmaceutics and Biopharmaceutics, 84(2):330-4
  23. Herd H, Daum N, Jones AT, Huwer H, Ghandehari H, Lehr CM (2013) Nanoparticle geometry and surface orientation influence mode of cellular uptake. American Chemical Society Nano, 7(3):1961-73
  24. Gustafson JA, Price RA, Frandsen J, Henak CR, Cappello J, Ghandehari H (2013) Synthesis and characterization of a matrix-metalloproteinase responsive silk-elastinlike protein polymer. Biomacromolecules, 14(3):618-25
  25. Thiagarajan G, Sadekar S, Greish K, Ray A, Ghandehari H (2013) Evidence of oral translocation of anionic G6.5 dendrimers in mice. Molecular Pharmacology, 10(3):988-98
  26. Gormley AJ, Larson N, Banisadr A, Robinson R, Frazier N, Ray A, Ghandehari H (2013) Plasmonic photothermal therapy increases the tumor mass penetration of HPMA copolymers. Journal of Controlled Release, 166(2):130-8
  27. Lee VH, Ghandehari H (2013) Advanced drug delivery perspectives and prospects. Preface. Advanced Drug Delivery Reviews, 65(1):1-2
  28. Jones CF, Campbell RA, Brooks AE, Assemi S, Tadjiki S, Thiagarajan G, Mulcock C, Weyrich AS, Brooks BD, Ghandehari H, Grainger DW (2012) Cationic PAMAM dendrimers aggressively initiate blood clot formation. American Chemical Society Nano, 6(11):9900-10
  29. Johnson S, Ko YK, Varongchayakul N, Lee S, Cappello J, Ghandehari H, Lee SB, Solares SD, Seog J (2012) Directed patterning of the self-assembled silk-elastin-like nanofibers using a nanomechanical stimulus. Chemical Communications (Cambridge), 48(86):10654-6
  30. Greish K, Thiagarajan G, Ghandehari H (2012) In vivo methods of nanotoxicology. Methods Molecular Biology, 926:235-53
  31. Gormley AJ, Larson N, Sadekar S, Robinson R, Ray A, Ghandehari H (2012) Guided Delivery of Polymer Therapeutics Using Plasmonic Photothermal Therapy. Nano Today, 7(3):158-167
  32. Larson N, Ghandehari H (2012) Polymeric conjugates for drug delivery. Chemistry of Materials, 24(5):840-853
  33. Yu T, Hubbard D, Ray A, Ghandehari H (2012) In vivo biodistribution and pharmacokinetics of silica nanoparticles as a function of geometry, porosity and surface characteristics. Journal of Controlled Release, 163(1):46-54
  34. Jones CF, Campbell RA, Franks Z, Gibson CC, Thiagarajan G, Vieira-de-Abreu A, Sukavaneshvar S, Mohammad SF, Li DY, Ghandehari H, Weyrich AS, Brooks BD, Grainger DW (2012) Cationic PAMAM dendrimers disrupt key platelet functions. Molecular Pharmacology, 9(6):1599-611
  35. Yu T, Greish K, McGill LD, Ray A, Ghandehari H (2012) Influence of geometry, porosity, and surface characteristics of silica nanoparticles on acute toxicity
  36. their vasculature effect and tolerance threshold. American Chemical Society Nano, 6(3):2289-301
  37. Frandsen JL, Ghandehari H (2012) Recombinant protein-based polymers for advanced drug delivery. Chemical Society Reviews, 41(7):2696-706
  38. Sadekar S, Ghandehari H (2012) Transepithelial transport and toxicity of PAMAM dendrimers implications for oral drug delivery. Advanced Drug Delivery Reviews, 64(6):571-88
  39. Price R, Gustafson J, Greish K, Cappello J, McGill L, Ghandehari H (2012) Comparison of silk-elastinlike protein polymer hydrogel and poloxamer in matrix-mediated gene delivery. International Journal of Pharmaceutics, 427(1):97-104
  40. Greish K, Thiagarajan G, Herd H, Price R, Bauer H, Hubbard D, Burckle A, Sadekar S, Yu T, Anwar A, Ray A, Ghandehari H (2012) Size and surface charge significantly influence the toxicity of silica and dendritic nanoparticles. Nanotoxicology, 6(7):713-23
  41. Gormley AJ, Malugin A, Ray A, Robinson R, Ghandehari H (2011) Biological evaluation of RGDfK-gold nanorod conjugates for prostate cancer treatment. Journal of Drug Targeting, 19(10):915-24
  42. Larson N, Greish K, Bauer H, Maeda H, Ghandehari H (2011) Synthesis and evaluation of poly(styrene-co-maleic acid) micellar nanocarriers for the delivery of tanespimycin. International Journal of Pharmaceutics, 420(1):111-7
  43. Gormley AJ, Greish K, Ray A, Robinson R, Gustafson JA, Ghandehari H (2011) Gold nanorod mediated plasmonic photothermal therapy a tool to enhance macromolecular delivery. International Journal of Pharmaceutics, 415(1-2):315-8
  44. Yu T, Malugin A, Ghandehari H (2011) Impact of silica nanoparticle design on cellular toxicity and hemolytic activity. American Chemical Society Nano, 5(7):5717-28
  45. Herd HL, Malugin A, Ghandehari H (2011) Silica nanoconstruct cellular toleration threshold in vitro. Journal of Controlled Release, 153(1):40-8
  46. Arnida, Janát-Amsbury MM, Ray A, Peterson CM, Ghandehari H (2011) Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. European Journal of Pharmaceutics and Biopharmaceutics, 77(3):417-23
  47. Gustafson JA, Ghandehari H (2010) Silk-elastinlike protein polymers for matrix-mediated cancer gene therapy. Advanced Drug Delivery Reviews, 62(15):1509-23
  48. Goldberg DS, Ghandehari H, Swaan PW (2010) Cellular entry of G3.5 poly (amido amine) dendrimers by clathrin- and dynamin-dependent endocytosis promotes tight junctional opening in intestinal epithelia. Pharmaceutical Research, 27(8):1547-57
  49. Pike DB, Ghandehari H (2010) HPMA copolymer-cyclic RGD conjugates for tumor targeting. Advanced Drug Delivery Reviews, 62(2):167-83
  50. Borgman MP, Ray A, Kolhatkar RB, Sausville EA, Burger AM, Ghandehari H (2009) Targetable HPMA copolymer-aminohexylgeldanamycin conjugates for prostate cancer therapy. Pharmaceutical Research, 26(6):1407-18
  51. Nan A, Bai X, Son SJ, Lee SB*, Ghandehari H* (2008) Cellular uptake and cytotoxicity of silica nanotubes. Nano Letters, 8(8):2150-4
  52. Dandu R, Ghandehari H (2007) Delivery of Bioactive Agents from Recombinant Polymers. Progress in Polymer Science, 32:1008-1030
  53. Kitchens KM, Foraker AB, Kolhatkar RB, Swaan PW, Ghandehari H (2007) Endocytosis and interaction of poly (amidoamine) dendrimers with Caco-2 cells. Pharmaceutical Research, 24(11):2138-45
  54. Mitra A, Coleman T, Borgman M, Nan A, Ghandehari H, Line BR (2006) Polymeric conjugates of mono- and bi-cyclic alphaVbeta3 binding peptides for tumor targeting. Journal of Controlled Release, 114(2):175-83
  55. Son SJ, Bai X, Nan A, Ghandehari H, Lee SB (2006) Template synthesis of multifunctional nanotubes for controlled release. Journal of Controlled Release, 114(2):143-52

to page top

Last Updated: 11/2/16