Characterization of Synthesized NANO-encapsulated Drug for Bone Loss on Hind Limb Suspension Rat Model by NMR and Micro-CT
Advances in Bioscience and Bioengineering
Volume 1, Issue 1, June 2013, Pages: 1-7
Received: Apr. 17, 2013;
Published: Jun. 14, 2014
Views 3160 Downloads 116
Qingwen Ni, Southwest Research Institute, San Antonio, TX, USA;Texas A&M International University, Laredo, TX, USA
Hong Dixon, Southwest Research Institute, San Antonio, TX, USA
Gloria Gutierrez, Southwest Research Institute, San Antonio, TX, USA
Long Bi, Southwest Research Institute, San Antonio, TX, USA
Yi-Xian Qin, State University of New York at Stony Brook, Stony Brook NY, USA
A formulation of nano-encapsulated enantiomer of (+) promethazine with desired release rate has been synthesized for establish a localized drug delivery system. It was tested on a hind limb suspension (HLS) disuse rat model, and by using a non-destructive Nuclear Magnetic Resonance (NMR) relaxation technique, and micro computed tomography (Micro-CT) analysis technique to qualitatively evaluate the effectiveness of the new bone formations as well as to compare the current commercial anti-bone loss drug Alendeonate. Our studies suggest that nano-encapsulated (+) promethazine in controlled release formulations conjugating bone-targeting functional groups are effective in promoting bone growth in a disuse rat model
Characterization of Synthesized NANO-encapsulated Drug for Bone Loss on Hind Limb Suspension Rat Model by NMR and Micro-CT, Advances in Bioscience and Bioengineering.
Vol. 1, No. 1,
2013, pp. 1-7.
B. L. Riggs and L. J. Melton, III. The prevention and treatment of osteoporosis. N.Engl.J.Med. 327:620-627,8-27-1992.
B. L. Riggs and L. J. Melton, III. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone. 17:505S-511S,1995.
Grigoriev, V. S. Oganov, A. V. Bakulin, V. V. Poliakov, L. I. Voronin, V. V. Morgun, V. S. Shnaider, L. V. Murashko, V. E. Novikov, A. LeBlanc, and L. Shackelford. Clinical and Psychological Evaluation of Bone Changes Among Astronauts after Long Term Space Flights (Russian). Aviakosmicheskaia I Ekologicheskaia Meditsina. 32:21-25,1998.
LeBlanc, V. Schneider, and L. Shackelford. Bone Mineral and Lean Tissue Loss after Long Duration Spaceflight. Trans.Amer.Soc.Bone Min.Res. 11S:567-1996.
LeBlanc, L. Shackelford, A. Feiveson, and V. Oganov. Bone Loss in Space: Shuttle/Mir Experience and Bed-Rest Counter Measure Program. 1:17-1999.
S. B. Arnaud. J. S. Harper, and M. Navidi. Mineral distribution in rat skeletons after exposure to a microgravity model.J.Gravit.Physiol. 2:115-116,1995.
H. Uludag, T. Gao, G. R. Wohl, D. Kantoci, and R. F. Zernicke. Bone affinity of a bisphosphonate-conjugated protein in vivo. Biotechnol.Prog. 16:1115-1118,2000.
H. Uludag and J. Yang. Targeting systemically administered proteins to bone by bisphosphonate conjugation. Biotechnol.Prog. 18:604-611,2002.
J. E. Wright, L. Zhao, P. Choi, and H. Uludag. Simulating hydroxyapatite binding of bone-seeking bisphosphonates. Adv.Exp.Med.Biol. 553:139-148,2004.
S.A. Gittens, G. Bansal, C. Kucharski, M. Borden, and H. Uludag. Imparting mineral affinity to fetuin by bisphosphonate conjugation: a comparison of three bisphosphonate conjugation schemes. Mol.Pharm. 2:392-406,2005
S. Zhang, J. E. Wright, G. Bansal, P. Cho, and H. Uludag. Cleavage of disulfide-linked fetuin-bisphosphonate conjugates with three physiological thiols. Biomacromolecules. 6:2800-2808,2005.
J. E. Wright, S. A. Gittens, G. Bansal, P. I. Kitov, D. Sindrey, C. Kucharski, and H. Uludag. A comparison of mineral affinity of bisphosphonate-protein conjugates constructed with disulfide and thioether linkages. Biomaterials. 27:769-784,2006.
T.J. Hall, H. Nyugen, M. Schaeublin, M. Michalsky, and M. Missbach. Phenothiazines are potent inhibitors of osteoclastic bone resorption. Gen.Pharmacol. 27:845-848,1996.
E. J. Boland, US patent application 2006/0258650 A1. Phenothiazine enantiomers as agents for the prevention of bone loss.2006
D. P. Gallegos, Munn, K., Smith, D. M., and Stermer, D. L. A NMR Technique for the Analysis of Pore Structure: Application to Materials with Well-Defined Pore Structure, J. Colloid Interface Sci 119 127.1987
C.L.Glaves and Smith D.M. Membrane Pore Structure Analysis Via NMR Spin-Lattice Relaxation Experiments, J. Member. Sci. 46 167. 1989
M.M. Chui, Philips, R.J., and McCarthy, M.Measurement of the Porous Microstructure of Hydrogels by Nuclear Magnetic Resonance, J. Colloid Interface Sci. 174 336.1995
W. E. Kenyon. Petrophysical Principles of Applications of NMR Logging, The Log Analyst, Mar.-Apr. 21.1997
X. Wang, and Ni, Q. 2003. Determination of Cortical Bone Porosity and Pore size Distribution Using a Field NMR Approach, J. Orthop. Res. 21(2): 312-319.
Q. Ni, King, J.D. and Wang, X.Characterization of Human Bone Structure Changes By Low Field NMR, Measurement Science and Technology, 15, 58 – 66. 2004.
P. Fantazzini, Bortolotti, V., Brown, R.J.S., Garavaglia, C., Viola, R., Giavaresi, G.Two 1H-nuclear magnetic resonance methods to measure internal porosity of bone trabeculae: By solid-liquid signal separation and by longitudinal relaxation. Journal of Applied Physics Vol 95, 339-343. 2004.
Q. Ni, and Nicolella, D.P. The Characterization of Human Cortical Bone Microdamage by Nuclear Magnetic Resonance. Measurement Science and Technology, 16, 659-668.2005
Q. Ni, Nyman, J., Wang, X., De Los Santos, A. and Nicolella, D.Assessment of Water Distribution Changes in Human Cortical Bones by Nuclear Magnetic Resonance. Measurement Science and Technology, 18, 715-723.2007
E. R. Morey-Holton, B. P. Halloran, L. P. Garetto, and S. B. Doty. Animal housing influences the response of bone to spaceflight in juvenile rats. J.Appl.Physiol. 88:1303-1309,2000
H.Y. Carr, and Purcell, E. M. Effects of Diffusion on Free Precession in Nuclear Magnetic Resonance Experiments. Phys. Rev. 904, No.3 630. 1954
S. Meiboom, and Gill, D. Modified Spin-Echo Method for Measuring Nuclear Relaxation Times. Rev. Sci. Inst. 29, 688. 1958
K.R. Broenstein and C.E. Tarr. Importance of Classical Difussion in NMR Studies of Water in Biological Cells. Phys Rev. A 19, 2446, 1979.
J. Kluge, F. Fusaro, N. Casas, M. Mazzotti, G. Muhrer. Production of PLGA micro- and nanocomposites by supercritical fluid extraction of emulsions: I. Encapsulation of lysozyme. The Journal of Supercritical Fluids, Volume 50, Issue 3, 327-335, 2009.