Modeling the molecular interactions of budesonide with bovine serum albumin guides the rational preparation of nanoparticles for pulmonary delivery

doi:10.5246/jcps.2018.06.042

Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (6): 415-428.DOI: 10.5246/jcps.2018.06.042

• Original articles • Previous Articles Next Articles

Modeling the molecular interactions of budesonide with bovine serum albumin guides the rational preparation of nanoparticles for pulmonary delivery

Shuai Meng¹, Wei Cui², Shaohui Lin¹, Guiling Wang¹, Yu Hei¹, Bo Deng¹, Shuang Ma¹, Zhan Zhang¹, Yingchun Liu³, Ying Xie^1*

1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
3. Soft Matter Research Center and Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, China

Received:2018-04-13 Revised:2018-05-18 Online:2018-06-30 Published:2018-05-23
Contact: Tel.: +86-010-82805351; Fax: +86-010-82802745, E-mail: bmuxieying@bjmu.edu.cn
Supported by:
The National Natural Science Foundation of China (Grant No. 81202469) and Founder of new drug research fund (Grant No. 20130527).

Abstract

Abstract:

Large Hollow nanoparticulate aggregates (LHNAs) based on albumin nanoparticles is a promising technology for developing dry powder inhaler (DPI) with good aerodynamic properties in order to provide a new drug delivery system (DDS) for the treatment of lung disease. Improved understanding of molecular interactions could lead to prepare the DDS rationally. Therefore, this investigation utilized computations and experiments to reveal the mechanisms of budesonide (BUD) interactions with bovine serum albumin (BSA) at the molecular level. The molecular dynamics (MD) simulation revealed that there were three critical stable binding sites of BUD on BSA (P1, P2, P3) mainly by hydrophobic interaction and hydrogen bond. The energydecomposition of each residue to the whole BUD-BSA complex system in P1-P3 showed that nonpolar residues in or around the binding site played an important role in the binding of BUD to BSA. The molar ratio was close to 3 in preparations in drug-loading efficiency experiment, which was confirmed to the simulation results. The details of the binding sites from computation provided a guideline for the design of the BSA nanoparticles carrying BUD, which was prepared successfully at last. Combination of the MD simulation and experiment as well as the mechanism of the molecular interaction provided a solid theoretical basis for the preparation of BSA-LHNAs for DPI in the future.

Key words: Molecular dynamics, Interaction mechanism, BSA nanoparticles, Budesonide, Rational preparation

CLC Number:

R943

Supporting:

Shuai Meng, Wei Cui, Shaohui Lin, Guiling Wang, Yu Hei, Bo Deng, Shuang Ma, Zhan Zhang, Yingchun Liu, Ying Xie. Modeling the molecular interactions of budesonide with bovine serum albumin guides the rational preparation of nanoparticles for pulmonary delivery[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(6): 415-428.

References

[1] Nicolai, T. Environmental air pollution and lung disease in children. Monaldi. Arch. Chest Dis. 1999, 54, 475-478.

[2] Katikireddi, S.V. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2015, 388, 1545-1602.

[3] Jones, M. Tailoring of corticosteroids in COPD management. Curr. Respir. Care Rep. 2014, 3, 121-132.

[4] Elks, J. The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 2014, 186, 1011.

[5] Azouz, W.; Chetcuti, P.; Hosker, H.S.; Saralaya, D.; Stephenson, J. The inhalation characteristics of patients when they use different dry powder inhalers. J. Aerosol Med. Pulm. D. 2015, 26, 35-42.

[6] Zhang, P.R.; Tu, Y.F.; Wang, S.; Wang, Y.H.; Xie, Y.; Li, M.; Jin, Y.G. Preparation and characterization of budesonide-loaded solid lipid nanoparticles for pulmonary delivery. J. Chin. Pharm. Sci. 2011, 20, 361-368.

[7] Hadinoto, K.; Phanapavudhikul, P.; Kewu, Z.; Tan, R.B. Dry powder aerosol delivery of large hollow nanoparticulate aggregates as prospective carriers of nanoparticulate drugs: effects of phospholipids. Int. J. Pharm. 2007, 333, 187-198.

[8] Gelamo, E.L.; Silva, C.H.; Imasato, H.; Tabak, M. Interaction of bovine (BSA) and human (HSA) serum albumins with ionic surfactants: spectroscopy and modelling. Biochim. Biophys. Acta. 2002, 1594, 84.

[9] Sung, J.C.; Pulliam, B.L.; Edwards, D.A. Nanoparticles for drug delivery to the lungs. Trends Biotechnol. 2007, 25, 563-570.

[10] Xie, Y.; Wang, Y.H.; Liu, C.; Tu, Y.F.; Ding, Y.; Xu, H.F. One interferon for pulmonary administration - a hollow nano-albumin aggregated particles. China: ZL 201310141203.8[P].

[11] Alder, B.J.; Wainwright, T.E. Studies in Molecular Dynamics. I. General Method. J. Chem. Phys. 1959, 31, 459.

[12] Lin, S.H.; Cui, W.; Wang, G.L; Meng, S.; Liu, Y.C.; Jin, H.W.; Zhang, L.R.; Xie, Y. Combined computational and experimental studies of molecular interactions of albuterol sulfate with bovine serum albumin for pulmonary drug nanoparticles. Drug Des. Devel. Ther. 2016, 10, 2973-2987.

[13] Luo, Q.; Wang, Y.H.; Yang, H.G.; Liu, C.; Ding, Y.; Xu, H.F.; Wang, Q.; Liu, Y.C.; Xie, Y. Modeling the Interaction of Interferon α-1b to Bovine Serum Albumin as a Drug Delivery System. J. Phys. Chem. B. 2014, 118, 8566-8574.

[14] Duan, Y.; Wu, C.; Chowdhury, S.; Lee, M.C.; Xiong, G.; Zhang, W.; Yang, R.; Cieplak, P.; Luo, R.; Lee, T.; Caldwell. J.; Wang, J.; Kollman, P. A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J. Comput. Chem. 2003, 24, 1999-2012.

[15] Jorgensen, W.L.; Chandrasekhar, J.; Madura, J.D.; Impey, R.W.; Klein, M.L. Comparison of Simple Potential Functions for Simulating Liquid Water. J. Chem. Phys. 1983, 79, 926-935.

[16] Kumari, R.; Kumar, R.; Lynn, A. g_mmpbsa-A GROMACS Tool for High-Throughput MM-PBSA Calculations. J. Chem. Inf. Model. 2014, 54, 1951-1962.

[17] Wang, Y.B.; Wang, J.C.; Meng, M.; Zhang, H. Preparation and evaluation of docetaxel-loaded albumin nanoparticles for intravenous administration. J. Chin. Pharm. Sci. 2010, 19, 214-222.

[18] Hao, H.; Ma, Q.; Huang, C.; He, F.; Yao, P. Preparation, characterization, and in vivo evaluation of doxorubicin loaded BSA nanoparticles with folic acid modified dextran surface. Int. J. Pharm. 2013, 444, 77-84.

[19] Weber, C.; Coester, C.; Kreuter, J.; Langer, K. Desolvation process and surface characterisation of protein nanoparticles. Int. J. Pharm. 2000, 194, 91-102.

[20] Volkamer, A.; Kuhn, D.; Rippmann, F.; Rarey, M. DoGSiteScorer: a web server for automatic binding site prediction, analysis and druggability assessment. Bioinformatics. 2012, 28, 2074-2075.

[21] Lobanov, M.; Bogatyreva, N.S.; Galzitskaia, O.V. Radius of gyration is indicator of compactness of protein structure. Mol. Biol. 2008, 42, 701-706.

[22] Falsafi-Zadeh, S.; Karimi, Z.; Galehdari, H. VMD DisRg: New User-Friendly Implement for calculation distance and radius of gyration in VMD program. Bio. Information. 2012, 8, 341-343.

[23] Grater, F.; Schwarzl, S.M.; Dejaegere, A.; Fischer, S.; Smith, J.C. Protein/ligand binding free energies calculated with quantum mechanics/molecular mechanics. J. Phys. Chem. B. 2005, 109, 10474-10483.

[24] Shooshtary, S.; Behtash, S.; Nafisi, S. Arsenic trioxide binding to serum proteins. J. Photochem. Photobiol. B. 2015, 148, 31-36.

[25] Yang, F.; Zhang, Y.; Liang, H. Interactive Association of Drugs Binding to Human Serum Albumin. Int. J. Mol. Sci. 2014, 15, 3580-3595.

[26] Joseph, K.S.; Moser, A.C.; Basiaga, S.B.G.; Schiel, J.E.; Hage, D.S. Evaluation of alternatives to warfarin as probes for Sudlow site I of human serum albumin Characterization by high-performance affinity chromatography. J. Chromatogr. A. 2009, 1216, 3492-3500.

[27] Conrad, M.L.; Moser, A.C.; Hage, D.S. Evaluation of indole-based probes for high-throughput screening of drug binding to human serum albumin: Analysis by high-performance affinity chromatography. J. Sep. Sci. 2009, 32, 1145-1155.

[28] Simard, J.R.; Zunszain, P.A.; Ha, C.E.; Yang, J.S.; Bhagavan, N.V.; Petitpas, I.; Curry, S.; Hamilton, J.A. Locating high-affinity fatty acid-binding sites on albumin by x-ray crystallography and NMR spectroscopy. P. Natl. Acad. Sci. 2005, 102, 17958-17963.

[29] Simard, J.R.; Zunszain, P.A.; Hamilton, J.A.; Curry, S. Location of high and low affinity fatty acid binding sites on human serum albumin revealed by NMR drug-competition analysis. J. Mol. Biol. 2006, 361, 336-351.

[30] Freitas, C.; Müller, R.H. Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN™) dispersions. Int. J. Pharm. 1998, 168, 221-229.

[31] Vishnu, P.; Roy, V. Safety and efficacy of nab-paclitaxel in the treatment of patients with breast cancer. Breast Cancer (Auckl). 2011, 5, 53-65.

[32] Edwards, D.A; Hanes, J.; Caponetti, G.; Hrkach, J.; Ben-Jebria, A.; Eskew, M.L; Mintzes, J.; Deaver, D.; Lotan, N.; Langer, R.; Large porous particles for pulmonary drug delivery. Science. 1997, 276, 1868-1871.

[33] Gharse, S.; Fiege, J. Large porous hollow particles: lightweight champions of pulmonary drug delivery. Curr. Pharm. Des. 2016, 22, 2463-2469.
[34] Anton, N.; Jakhmola, A.; Vandamme, T.F. Trojan microparticles for drug delivery. Pharmaceutics. 2012, 4, 1-25.

Modeling the molecular interactions of budesonide with bovine serum albumin guides the rational preparation of nanoparticles for pulmonary delivery

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