发布: 2021年03月20日第11卷第6期 DOI: 10.21769/BioProtoc.3959 浏览次数: 5118
评审: Xingmin ZhangAnonymous reviewer(s)
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Abstract
Many new drug development candidates are highly lipophilic compounds with low water solubility. This constitutes a formidable challenge for the use of such compounds for cancer therapy, where high doses and intravenous injections are needed (Di et al., 2012). Here, we present a poly(2-oxazoline) polymer (POx)-based nanoformulation strategy to solubilize and deliver hydrophobic drugs. POx micelles are prepared by a simple thin-film hydration method. In this method, the drug and polymer are dissolved in a common solvent and allowed to mix, following which the solvent is evaporated using mild heating conditions to form a thin film. The micelles form spontaneously upon hydration with saline. POx nanoformulation of hydrophobic drugs is unique in that it has a high drug loading capacity, which is superior to micelles of conventional surfactants. Moreover, multiple active pharmaceutical ingredients (APIs) can be included within the same POx micelle, thereby enabling the codelivery of binary as well as ternary drug combinations (Han et al., 2012; He et al., 2016).
Keywords: Lipophilic (亲脂性的)Background
Recent statistics show that only 3.7% of the new drug candidates that enter clinical testing are approved for use in cancer treatment. This has been primarily attributed to the poor pharmacokinetics of poorly water-soluble drug candidates, which results in suboptimal performance (Gala et al., 2020). POx polymeric micelles offer several advantages over traditional drug delivery systems such as liposomes, microparticles, and nanogels, among others. The unparalleled high solubilizing capacity of POx micelles for a large variety of hydrophobic drugs enables the delivery of greater amounts of drugs with a substantially lesser amount of excipient (Luxenhofer et al., 2010, He et al., 2016). POx-based drug formulations are easy to prepare, safe, and stable. Additionally, a quantitative structure-property relationship (QSPR) model has been developed to predict drug loading into POx micelles, which can be utilized to facilitate high throughput screening of sparingly soluble drug development candidates for incorporation in POx micelles (Alves et al., 2019).
Materials and Reagents
PVC tubing (Nalgene, 1/4” ID )
Eppendorf tubes (Fisher Scientific, catalog number: 05-408-129 )
Pipette tips (Fisher Scientific)
11 mm plastic autosampler vials (Thermo Scientific, catalog number: C4011-13 )
UV cuvettes (Fisher Scientific, catalog number: NC0628994 )
0.2-micron syringe filter, Nylon (Fisherbrand, catalog number: 13100108 )
Poly(2-oxazoline) triblock copolymer (P[MeOx37-b-BuOx23-b-MeOx37]-piperazine) was synthesized as described previously (Luxenhofer et al., 2010)
Drugs were purchased from either Adooq Bioscience, Apex Bio, or LC laboratories and stored at -20 °C
Ethanol 200 proof (Fisher Scientific)
Normal Saline (Teknova, catalog number: S5815 )
Equipment
Pipettes (Fisher Scientific)
Sonicator (Branson 2510 ultrasonic bath)
Eppendorf heating block (Fisher Scientific, catalog number: 11-715-1250 )
Desiccator (LabCorp)
Rotor vacuum evaporator (Buchi)
Vortex mixer (Fisher Scientific, catalog number: 02215365 )
Benchtop microcentrifuge (Thermo Scientific)
Eppendorf Centrifuge Minispin (Fisher Scientific, catalog number: 05-090-100 )
HPLC (Agilent 1200 series)
Zetasizer (Malvern)
Procedure
文章信息
版权信息
© 2021 The Authors; exclusive licensee Bio-protocol LLC.
如何引用
Vinod, N., Hwang, D., Azam, S. H., Van Swearingen, A. E. D., Wayne, E., Fussell, S. C., Sokolsky-Papkov, M., Pecot, C. V. and Kabanov, A. V. (2021). Preparation and Characterization of Poly(2-oxazoline) Micelles for the Solubilization and Delivery of Water Insoluble Drugs. Bio-protocol 11(6): e3959. DOI: 10.21769/BioProtoc.3959.
分类
癌症生物学 > 通用技术 > 药物发现和分析
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