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Applied Sciences-Basel · 2019 ·Vol. 9 ·期 8 ·1638 · IF 2.217

Injectable Vaginal Hydrogels as a Multi-Drug Carrier for Contraception

Lei Nie,Peng Zou,Jing Dong,Meng Sun,Peng Ding,Yanting Han,Chingching Ji,Qiuju Zhou,Hongyu Yuan,Jinping Suo

Injectable intravaginal hydrogels could deliver drugs systemically without hepatic first pass effect. This paper focuses on the contraceptive function of an injectable temperature-sensitive four-arm star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (4sPLGA-mPEG) block copolymer hydrogels as a carrier of three drugs. In vitro controlled release profiles were investigated via HPLC, and it showed that the cumulative release amounts of indomethacin (IMC), gestodene (GSD), and ethinyl estradiol (EE) from copolymer hydrogels could be regulated by adjusting the lactide/glycolide (LA/GA) mol ratio. In addition, in vitro release profiles of IMC, GSD, and EE well corresponded to Higuchi model. The acute toxicity of copolymer hydrogels loaded with different dosage contents multi-drug was evaluated in vivo. As to the high dosage group, the uterus was hydropic at day 1 and ulcerated at day 5, followed with intestinal adhesion. Regarding the middle dosage group, no festering of tissues was observed and, blood coagulum existed in the uterus at different days. For low dosage group, no significant tissue necrosis was found. Finally, the antifertility experiments confirmed that hydrogels loaded with the multi-drug had an excellent contraceptive effect. The above results indicated that injectable copolymer hydrogel as a multi-drug carrier was promising as a novel contraception method.Keywords:vaginal hydrogels;injectable;contraception;multi-drug release;mucoadhesive;biodegradability

CAS / MDL: 53-86-1
研究领域: 药学 · 生殖健康 · 聚合物化学 · 药物递送系统
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Regenerative Biomaterials · 2020 ·Vol. 7 ·期 4 ·381-390 · IF 4.882

Hierarchically electrospraying a PLGA@chitosan sphere-in-sphere composite microsphere for multi-drug-controlled release

Liu Zhu,Ye Weilong,Zheng Jingchuan,Wang Qindong,Ma Guowu,Liu Huiying,Wang Xiumei

Sequential administration and controlled release of different drugs are of vital importance for regulating cellular behaviors and tissue regeneration, which usually demands appropriate carriers like microspheres (MS) to control drugs releases. Electrospray has been proven an effective technique to prepare MS with uniform particle size and high drug-loading rate. In this study, we applied electrospray to simply and hierarchically fabricate sphere-in-sphere composite microspheres, with smaller poly(lactic-co-glycolic acid) MS (∼8–10 μm in diameter) embedded in a larger chitosan MS (∼250–300 μm in diameter). The scanning electron microscopy images revealed highly uniform MS that can be accurately controlled by adjusting the nozzle diameter or voltage. Two kinds of model drugs, bovine serum albumin and chlorhexidine acetate, were encapsulated in the microspheres. The fluorescence-labeled rhodamine-fluoresceine isothiocyanate (Rho-FITC) and ultraviolet (UV) spectrophotometry results suggested that loaded drugs got excellent distribution in microspheres, as well as sustained, slow release in vitro. In addition, far-UV circular dichroism and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) results indicated original secondary structure and molecular weight of drugs after electrospraying. Generally speaking, our research proposed a modified hierarchically electrospraying technique to prepare sphere-in-sphere composite MS with two different drugs loaded, which could be applied in sequential, multi-modality therapy.

研究领域: 生物材料学 · 药物递送系统 · 组织工程
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ACS Applied Materials & Interfaces · 2017 · IF 7.504

Tri-Needle Coaxial Electrospray Engineering of Magnetic Polymer Yolk–Shell Particles Possessing Dual-Imaging Modality, Multiagent Compartments, and Trigger Release Potential

Chunchen Zhang,Zhi-Cheng Yao,Qiuping Ding,James J. Choi,Zeeshan Ahmad,Ming-Wei Chang,Jing-Song Li

Particulate platforms capable of delivering multiple actives as well as providing diagnostic features have gained considerable interest over the last few years. In this study, magnetic polymer yolk–shell particles (YSPs) were engineered using a tri-needle coaxial electrospraying technique enabling dual-mode (ultrasonic and magnetic resonance) imaging capability with specific multidrug compartments via an advanced single-step encapsulation process. YSPs comprised magnetic Fe3O4 nanoparticles (MNPs) embedded in the polymeric shell, an interfacing oil layer, and a polymeric core (i.e., composite shell–oil interface–polymeric core). The frequency of the ultrasound backscatter signal was modulated through YSP loading dosage, and both T1- and T2-weighted magnetic resonance imaging signal intensities were shown to decrease with increasing MNP content (YSP outer shell). Three fluorescent dyes (selected as model probes with varying hydrophobicities) were coencapsulated separately to confirm the YSP structure. Probe release profiles were tuned by varying power or frequency of an external auxiliary magnetic field (AMF, 0.7 mT (LAMF) or 1.4 mT (HAMF)). In addition, an “inversion” phenomenon for the AMF-enhanced drug release process was studied and is reported. A low YSP cytotoxicity (5 mg/mL) and biocompatibility (murine, L929) was confirmed. In summary, magnetic YSPs demonstrate timely potential as multifunctional theranostic agents for dual-imaging modality and magnetically controlled coactive delivery.

研究领域: 材料科学 · 医学影像 · 药物递送
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Journal of Materials Chemistry B · 2023 · IF 7

Zwitterionic nanocapsule-based wound dressing with the function of gradient release of multi-drugs for efficient wound healing

Jiahui Zhou,Kaishun Xia,Yuting Li,Shihua Mao,Yucong Gu,Mengjie Si,Shuaibing Wang,Guangyan Du,Yisheng Xu,Dong Zhang,Si Yu Zheng,Jintao Yang

Efficient wound healing has attracted great interest due to the prevalence of skin damage. It is still highly desired yet challenging to construct a multi-drug loaded wound dressing that can release different drugs at different times to meet specific requirements towards different healing stages. Herein, a wound dressing was developed based on thermoresponsive zwitterionic nanocapsules (ZNs) that were sandwiched between two double-layered fabrics to regulate the multiple drug release pathway. The salt-response of the obtained ZNs was greatly suppressed while its transition temperature was regulated to be ∼37 °C to fit the needs of the physiological environment. Two bioactive substances, human basic fibroblast growth factor (bFGF) for tissue regeneration and norfloxacin for anti-inflammation, were loaded in the ZNs and on the surface of fabrics, respectively, to achieve separative gradient release. The in vitro drug release tests revealed that norfloxacin could be released relatively fast (∼24 h) while the release rate of bFGF was much slower (∼168 h), matching the specific time requirements of inflammation and proliferation stages very well. The in vivo wound healing experiment also confirmed the high wound healing efficiency of the wound dressing developed here, compared to the wound dressings without gradient release characteristics. We believe the strategy illustrated here will provide new insights into the design and biomedical applications of zwitterionic nanocapsules.

研究领域: 材料科学 · 生物医学工程 · 药学 · 组织工程
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Pharmaceutics · 2023 ·Vol. 15 ·期 9 ·2336 · IF 5.4

Three-Dimensional Printing Multi-Drug Delivery Core/Shell Fiber Systems with Designed Release Capability

Hao Wei,Yongxiang Luo,Ruisen Ma,Yuxiao Li

A hydrogel system with the ability to control the delivery of multiple drugs has gained increasing interest for localized disease treatment and tissue engineering applications. In this study, a triple-drug-loaded model based on a core/shell fiber system (CFS) was fabricated through the co-axial 3D printing of hydrogel inks. A CFS with drug 1 loaded in the core, drug 2 in the shell part, and drug 3 in the hollow channel of the CFS was printed on a rotating collector using a co-axial nozzle. Doxorubicin (DOX), as the model drug, was selected to load in the core, with the shell and channel part of the CFS represented as drugs 1, 2, and 3, respectively. Drug 2 achieved the fastest release, while drug 3 showed the slowest release, which indicated that the three types of drugs printed on the CFS spatially can achieve sequential triple-drug release. Moreover, the release rate and sustained duration of each drug could be controlled by the unique core/shell helical structure, the concentration of alginate gels, the cross-linking density, the size and number of the open orifices in the fibers, and the CFS. Additionally, a near-infrared (NIR) laser or pH-responsive drug release could also be realized by introducing photo-thermal materials or a pH-sensitive polymer into this system. Finally, the drug-loaded system showed effective localized cancer therapy in vitro and in vivo. Therefore, this prepared CFS showed the potential application for disease treatment and tissue engineering by sequential- or stimulus-responsively releasing multi-drugs.Keywords:3D printing;multi-drug delivery;core/shell fibers;on-demand release

研究领域: 生物医学工程 · 药学 · 材料科学 · 组织工程
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

Programmed-stimuli responsive carrier-free multidrug delivery system for highly efficient trimodal combination therapy

Jun Zhou,Kangjing Li,Hejia Qin,Beibei Xie,Haiqin Liao,Xiaoping Su,Cuiping Li,Xuan He,Wenxia Chen,Xinglu Jiang

Programmed response, carrier-free, and multimodal therapy drug delivery systems (DDS) are promising solutions to multidirectional cytotoxic effects, inefficient antitumor, and severe side effects for cancer therapy. Here, three widely used clinical drugs, interferon α1b (IFNα1b), indocyanine green (ICG), and doxorubicin (DOX), were prepared into carrier-free DDS IFNα1b-ICG-DOX (IID) by a simple one-step method without additional any reagents. IID can achieve smart and programmed DDS by combining low pH and near-infrared (NIR) light stimuli-responsive controlled release. In pH = 7.4 environments, our IID is about 380 nm in size with negative charge rounded particles; while they enter into the acid environment (pH < 7), hydrogen ions (H + ) trigger DOX release, their size becomes larger and the surface charge turns positive. These larger particles are rapidly disintegrated after exposure to NIR light and then the remaining DOX, IFNα1b, and ICG are released. In vivo, the IID with larger size and positive charge resulting from low pH is is easy to accumulate in tumor tissue. Tumors can be exposed to NIR light when needed to control the release of these three drugs. Hence, DOX, ICG, and IFNα1b can be enriched in the tumor to the high efficiency of combined chemotherapy, photothermal therapy, and immunotherapy.

研究领域: 药学 · 生物医学工程 · 癌症治疗 · 药物递送系统
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