Combined computational and experimental studies of molecular interactions of albuterol sulfate with bovine serum albumin for pulmonary drug nanoparticles.
Albumin-based nanoparticles (NPs) are a promising technology for developing drug-carrier systems, with improved deposition and retention profiles in lungs. Improved understanding of these drug-carrier interactions could lead to better drug-delivery systems. The present study combines computational and experimental methods to gain insights into the mechanism of binding of albuterol sulfate (AS) to bovine serum albumin (BSA) on the molecular level. Molecular dynamics simulation and surface plasmon resonance spectroscopy were used to determine that there are two binding sites on BSA for AS: the first of which is a high-affinity site corresponding to AS1 and the second of which appears to represent the integrated functions of several low-affinity sites corresponding to AS2, AS3, and AS8. AS1 was the strongest binding site, established via electrostatic interaction with Glu243 and Asp255 residues in a hydrophobic pocket. Hydrogen bonds and salt bridges played a main role in the critical binding of AS1 to BSA, and water bridges served a supporting role. Based upon the interaction mechanism, BSA NPs loaded with AS were prepared, and their drug-loading efficiency, morphology, and -release profiles were evaluated. Successful clinical development of AS-BSA-NPs may improve therapy and prevention of bronchospasm in patients with reversible obstructive airway disease, and thus provide a solid basis for expanding the role of NPs in the design of new drug-delivery systems.
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University.
Shao-Hui
SH
Lin
School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing.
Wei
W
Cui
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University.
Gui-Ling
GL
Wang
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University.
Shuai
S
Meng
Soft Matter Research Center, Department of Chemistry, Zhejiang University, Hangzhou.
Ying-Chun
YC
Liu
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People's Republic of China.
Hong-Wei
HW
Jin
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People's Republic of China.
Liang-Ren
LR
Zhang
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People's Republic of China.
Ying
Y
Xie
D000420:Albuterol / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001665:Binding Sites; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011789:Quantum Theory; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry*; D020349:Surface Plasmon Resonance / Q000295:instrumentation
D004337:Drug Carriers; D012710:Serum Albumin, Bovine; D000420:Albuterol
BSA nanoparticles; drug delivery systems; interaction mechanism; molecular dynamics; surface plasmon resonance
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