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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2014 · IF 3.005

Investigation on fabrication process of dissolving microneedle arrays to improve effective needle drug distribution

Qingqing Wang,Gangtao Yao,Pin Dong,Zihua Gong,Ge Li,Kejian Zhang,Chuanbin Wu

The dissolving microneedle array (DMNA) offers a novel potential approach for transdermal delivery of biological macromolecular drugs and vaccines, because it can be as efficient as hypodermic injection and as safe and patient compliant as conventional transdermal delivery. However, effective needle drug distribution is the main challenge for clinical application of DMNA. This study focused on the mechanism and control of drug diffusion inside DMNA during the fabrication process in order to improve the drug delivery efficiency. The needle drug loading proportion (NDP) in DMNAs was measured to determine the influences of drug concentration gradient, needle drying step, excipients, and solvent of the base solution on drug diffusion and distribution. The results showed that the evaporation of base solvent was the key factor determining NDP. Slow evaporation of water from the base led to gradual increase of viscosity, and an approximate drug concentration equilibrium was built between the needle and base portions, resulting in NDP as low as about 6%. When highly volatile ethanol was used as the base solvent, the viscosity in the base rose quickly, resulting in NDP more than 90%. Ethanol as base solvent did not impact the insertion capability of DMNAs, but greatly increased the in vitro drug release and transdermal delivery from DMNAs. Furthermore, the drug diffusion process during DMNA fabrication was thoroughly investigated for the first time, and the outcomes can be applied to most two-step molding processes and optimization of the DMNA fabrication.

CAS / MDL: 9048-71-9 9004-54-0
研究领域: 药学 · 生物医学工程
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Acta Biomaterialia · 2022 · IF 10.633

A wearable gamma radiation-responsive granulocyte colony-stimulating factor microneedle system protecting against ionizing radiation-induced injury

Xiang Yu,Lin Zhu,Xiaohui Liang,Bochuan Yuan,Minshu Li,Shen Hu,Pingtian Ding,Lina Du,Junwang Guo,Yiguang Jin

Exposure to a nuclear accident or a radiological attack may cause serious death events due to ionizing radiation-induced injury and acute radiation syndrome (ARS). Recombinant human granulocyte colony-stimulating factor (G-CSF) is now used for the treatment of ARS. However, the current injection formulation might not ensure treatment as early as possible after a nuclear accident, resulting in a decrease in therapeutic efficiency. In the present study, we have developed a G-CSF wearable system (GWS) consisting of a commercial microchip, a temperature sensor , a gamma-ray detection sensor, a flexible heater, and a G-CSF temperature-sensitive microneedle (GTSMN) patch. G-CSF-containing hyaluronic acid solutions were cast into the mold to obtain G-CSF microneedles (GMNs), which were coated with a temperature-sensitive layer of dodecanoic acid-cetylamine salt to obtain GTSMNs. The flexible heater was prepared by jet printing Ag nanoparticle inks. The GWS and its components are explored and optimized in the aspects of electronics, mechanics, heat transfer and drug diffusion . The γ radiation signal is sensitively monitored by the GWS. The wearable G-CSF system immediately releases G-CSF into the body in response to signal feedback and provides maximal protection against ionizing radiation-induced injury. Therefore, the GWS is a promising wearable system against emergent ionizing radiation injury. Statement of significance Ionizing radiation-induced injury is always the very important public health problem all the global people care. Some medicines have been applied to protect the body from the injury. Unfortunately, sometimes the injuries accidently happen and the medicines cannot be administered in time, leading to serious acute radiation syndrome. Here, we design a wearable system loading G-CSF that has been approved by FDA to protect the body from ionizing radiation-induced injury. This system consists of a commercial microchip, a temperature sensor, a Gamma-ray detection sensor, a flexible heater, and a G-CSF temperature-sensitive microneedle patch. It can monitor γ radiation and immediately release G-CSF into the body to protect the body to the maximal extent. Therefore, the system is a promising wearable medical device against emergent ionizing radiation injury.

研究领域: 生物医学工程 · 辐射防护 · 药物传递系统 · 材料科学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Coaxial microfluidic spinning design produced high strength alginate membranes for antibacterial activity and drug release

Ying Zhang,Ting-Ting Li,Zhike Wang,Bing-Chiuan Shiu,Jia-Horng Lin,Ching-Wen Lou

Directional drug delivery and sufficient strength are two conditions that need to be met for wound dressing. In this paper, an oriented fibrous alginate membrane with sufficient strength was constructed via coaxial microfluidic spinning, and zeolitic imidazolate framework-8/ascorbic acid was used to realize drug delivery and antibacterial activity. The effects of the process parameters of the coaxial microfluidic spinning on the mechanical properties of the alginate membrane were discussed. In addition, it was found that the antimicrobial activity mechanism of zeolitic imidazolate framework-8 was attributed to the disruptive effect of reactive oxygen species (ROS) on bacteria, and the quantitative amount of generated ROS were evaluated by detecting •OH and H 2 O 2 . Furthermore, a mathematical drug diffusion model was established and showed high consistency with the experimental data (R 2  = 0.99). This study provides a new idea for the preparation of dressing materials with high strength and directional drug delivery and also provides some guidance for the development of coaxial microfluidic spin technology to be used in functional materials for drug release.

CAS / MDL: 138-89-6
研究领域: 材料科学 · 生物医学工程 · 药学
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iScience · 2023 · IF 5.8

Vertical impedance electrode array for spatiotemporal dynamics monitoring of 3D cells under drug diffusion effect

Yong Qiu,Xin Liu,Yuxuan Zhu,Deming Jiang,Fengheng Li,Weijie Yu,Hao Wan,Liujing Zhuang,Yuxiang Pan,Ping Wang

Although three-dimensional (3D) tumor models feature more accurate responses to drugs, the Matrigel scaffold affects the drug diffusion effect. Obtaining accurate drug spatiotemporal response characteristics is of great significance in the drug screening domain. However, the conventional cell-based sensors are difficult to perform spatiotemporal dynamics impedance monitoring of 3D cells and evaluate the anti-cancer pharmacological effect. Here, we proposed a biosensing platform involving a vertical impedance electrode array (VIEA) chip and a multichannel detection system. The platform can dynamically record 3D cell impedance in the vertical direction, which is consistent with time- and location-dependent drug penetration, closely related to spatiotemporal cell viability under drug effects. The subtle changes of impedance signals in different locations induced by drug diffusion can be detected, which demonstrates its high performance in drug systematic evaluation. The universal and high-content 3D cell biosensing platform is believed to have promising potential in pharmacodynamics investigation and preclinical drug screening.

研究领域: 生物医学工程 · 药学 · 细胞生物学 · 药物发现
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