INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Dai-Xu Wei,Duanfang Cai,Youguo Tan,Kezhi Liu,Jin-Wei Dao,Xiang Li,Aikeremujiang Muheremu
Huperzine A (HupA) is used in Alzheimer's disease (AD) therapy for its effective inhibition of acetylcholinesterase (AChE) and enhancement of cholinergic neuronal function. However, direct oral administration and injection of HupA cause side effects like nausea, anorexia, and rapid metabolism. Using a tripolymer, poly(3-hydroxybutyrate- co -3-hydroxyvalerate-co-3-hydroxyhexanoate (PBVHx), from the polyhydroxyalkanoate (PHA) family synthesized via synthetic biology, we present a novel AD therapy strategy with peritoneally administered PBVHx microspheres loaded with HupA (HupA-PBVHxMs). This approach extends HupA's metabolic duration in the blood and brain, enhancing AChE inhibition efficacy. Uniformly sized HupA-PBVHxMs, created using microfluidics and rotary evaporation, show up to 70.4 % drug encapsulation efficiency, sustained HupA release for 40 days, reduced neurotoxicity from Aβ25–35, and maintained in vivo HupA supply and AChE inhibition for over 20 days. In cognitive tests, HupA-PBVHxMs improved function in AD mice. Thus, PBVHx microspheres with slower HupA release and lower biotoxicity offer a superior platform for sustained AChE inhibitor release, outperforming commercial PLGA microspheres.
研究领域:
药学
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神经科学
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生物技术
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
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2024
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IF 9.5
Zhu Shengjie,Huang Danqing,Luan Qichen,Li Yang,Gan Jingjing,Zhao Yuanjin,Sun Lingyun
Macrophages play a pivotal role in systemic lupus erythematosus (SLE) therapy. Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization. Here, we present a novel hyaluronic acid methacrylate (HAMA) hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions. The HAMA microparticles loaded with monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) were fabricated by using a microfluidic technology. The released MCP-1 facilitates the aggregation of inflammatory macrophages, after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2, thus restoring immune balance. We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery, modulate immune function, and attenuate the disease symptoms. These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.
研究领域:
药理学
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免疫学
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生物医学工程
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药物递送系统
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自身免疫疾病
✓ 已验证
DOI
高影响因子
ACS Nano
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2024
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IF 15.8
Shu Liang,Lingyun Xiao,Tian Chen,Paola Roa,Emiliano Cocco,Zhangwen Peng,Liu Yu,Meiying Wu,Jie Liu,Xizhe Zhao,Wenbin Deng,Xiongjun Wang,Chao Zhao,Yang Deng,Yang Mai
Intraperitoneal co-delivery of chemotherapeutic drugs (CDs) and immune checkpoint inhibitors (ICIs) brings hope to improve treatment outcomes in patients with peritoneal metastasis from ovarian cancer (OC). However, current intraperitoneal drug delivery systems face issues such as rapid drug clearance from lymphatic drainage, heterogeneous drug distribution, and uncontrolled release of therapeutic agents into the peritoneal cavity. Herein, we developed an injectable nanohydrogel by combining carboxymethyl chitosan (CMCS) with bioadhesive nanoparticles (BNPs) based on polylactic acid-hyperbranched polyglycerol. This system enables the codelivery of CD and ICI into the intraperitoneal space to extend drug retention. The nanohydrogel is formed by cross-linking of aldehyde groups on BNPs with amine groups on CMCS via reversible Schiff base bonds, with CD and ICI loaded separately into BNPs and CMCS network. BNP/CMCS nanohydrogel maintained the activity of the biomolecules and released drugs in a sustained manner over a 7 day period. The adhesive property, through the formation of Schiff bases with peritoneal tissues, confers BNPs with an extended residence time in the peritoneal cavity after being released from the nanohydrogel. In a mouse model, BNP/CMCS nanohydrogel loaded with paclitaxel (PTX) and anti-PD-1 antibodies (αPD-1) significantly suppressed peritoneal metastasis of OC compared to all other tested groups. In addition, no systemic toxicity of nanohydrogel-loaded PTX and αPD-1 was observed during the treatment, which supports potential translational applications of this delivery system.
研究领域:
药学
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生物医学工程
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肿瘤学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）