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Amphiphilic small molecular mates match hydrophobic drugs to form nanoassemblies based on drug-mate strategy

Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 129-138页

作者： Leiqiang Han Shuang Liang Weiwei Mu Zipeng Zhang Limin Wang Shumin Ouyang Bufan Yao Yongjun Liu Na Zhang Department of Pharmaceutics Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, the drug is a hydrophobic drug that is poorly soluble in water, and the mate is an amphiphilic small molecule (SMA) that has both hydrophilic and lipophilic properties. We proposed that the hydrophobic drug could co-assemble with a suitable SMA on a nanoscale without additive agents. The proof-ofconcept methodology and results were presented to support our hypothesis. We selected five hydrophobic drugs and more than ten amphiphilic small molecules to construct a library. Through molecular dynamic simulation and quantum chemistry computation,we speculated that the formation of nanoassemblies was related to the binding energy of the drug-mate, and the drug-mate interaction must overcome drug-drug ***, the obtained SF/VECOONa nanoassemblieswas selected as a model, which had an ultra-high drug loading content (46%), improved pharmacokinetics, increased bioavailability, and enhanced therapeutic efficacy. In summary, the drug-mate strategy is an essential resource to design exact SMA for many hydrophobic drugs and provides a reference for the design of a carrier-free drug delivery system.

关键词： drug-mate strategy Molecular level hydrophobic drug Small molecular mate Nanoassemblies

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Preparation and Characterization of Florfenicol/Chitosan-stearic Acid Polymer Nanomicelle and Its Antibiotic Properties

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Journal of Wuhan University of Technology(Materials Science) 2018年第4期33卷 1007-1013页

作者：齐晓丹 JIA Xile 宋益民 Department of Pharmaceutical Engineering Qingdao University of Science&TechnologyQingdao 266042China E E-Jiao Co. Ltd.Liaocheng 252200China

Amphiphilic CS-SA polymers were prepared using the SA modified by small molecule water-soluble chitosan, and CS-SA nanomicelles and FF/CS-SA nanomicelles were prepared by using CSSA polymers as the material with dialysis-ultrasound method. CS-SA polymers, CS-SA nanomicelles, and FF/CS-SA nanomicelles were characterized by FT-IR, TGA, and SEM. Results showed that the SA was grafted to the amino of CS by amide bond. CS-SA nanomicelles and FF/CS-SA nanomicelles were spherical, smooth without fold. The influence of different molar ratio of FF to CS-SA polymers on the encapsulation efficiency and drug-loading rate determined the best molar ratio that was 1：1.09. In vitro release experiments, drug release performance study found that hydrophobic drug releasing from FF/CS-SA nanomicelles presented sustainedrelease. In vitro bacteriostasis experiments, when the concentration was higher than 4.98 mg/mL, FF/CSSA nanomicelles had antibacterial action and a positive correlation with concentration. The results revealed that amphiphilic chitosan derivative nanomicelles were carriers with broad prospects, increasing solubility of hydrophobic drugs and presenting sustained release for hydrophobic drugs, which provided a new research idea for drug delivery and targeted drug delivery of hydrohobic drugs.

关键词： nanomicelle water-soluble chitosan hydrophobic drug antibacterial activity

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