DRUG DELIVERY
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2020
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IF 4.902
Dongmei Wang,Mengmeng Luo,Baoshan Huang,Wa Gao,Yan Jiang,Qing Li,Kaihui Nan,Sen Lin
Following the traumatic axonal injury in the optic nerve, the failure of retrograde axonal transport to continuously supply neurotrophins from the brain to retina results in deprivation of neurotrophins in retinal ganglion cells (RGCs), which in turn can modulate the fate of RGCs toward apoptosis and thereby impede axon regeneration. In this study, a ciliary neurotrophic factor (CNTF) loaded thermo-sensitive hydrogel was designed and developed as a localized drug depot to restore neurotrophins supply following axon injury. Besides, following traumatic axon injury, overactive immune responses cause neurotoxicity and induce scar formation which together constitutes the major hindrances for axon regeneration. Thus, the FK506, a hydrophobic macrolide immunosuppressant, was co-loaded into the hydrogel after encapsulating it into a polymeric micelle. The materials can undergo sol-to-gel transition within minutes under a physiological pH of 37 °C. The release of drugs from the hydrogel exhibited a sustainable profile in vitro. The optic nerve was exposed by surgical procedure and the animal model was prepared by crushing the nerve with a reverse clamp. For the localized delivery to the optic nerve, a pre-hydrogel liquid containing chitosan, FK506 (in micelle), CNTF, and the gelling agent was directly smeared on the injured site, which gelled under physiological condition. This co-delivery system exhibited in vivo RGCs protective effect against the adverse effects caused by traumatic optic nerve injury, indicating the potential of this drug delivery system for effective optic nerve repair and this strategy may provide promising platforms for localized drug delivery in various other therapies.
研究领域:
神经科学
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药学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
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2025
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IF 12.9
Xiaobin Ren,Qinying Huang,Zhenyuan Xie,Zhirong Liu,Jinfei Wei,Jianming Zheng,Zhixing Li,Zhaorong Wang,Ting Li,Ziwen Chen,Qingqing Yao,Wencan Wu
Neuroinflammation microenvironment and retinal ganglion cell (RGC) apoptosis are two critical barriers to axonal regeneration following traumatic optic neuropathy (TON). To overcome these challenges, we developed an innovative dual drug delivery strategy utilizing oriented porous nanofiber (OF) and ciliary neurotrophic factor (CNTF)-loaded delivery systems, aiming to promote axonal regeneration and restore RGC survival. Cerium oxide nanoparticles (Ce NPs) were physically mixed with poly(L-lactic acid)/polycaprolactone (PLA/PCL) solution to prepare oriented porous nanofibers (OF-Ce) via electrospinning and solvent evaporation techniques. The aligned porous nanofiber architecture supports drug loading, guides cell directional growth, and integrates Ce NPs properties to modulate the neuroinflammatory environment. Subsequently, neural stem cell-derived exosomes (NSC Exo) were applied onto the porous OF-Ce nanofiber microtubule (OF-Ce/Exo), stabilizing exosomes, improving hydrophilicity, and significantly reducing neuroinflammation while inhibiting glial scar formation. Importantly, these OF-Ce/Exo microtubules effectively guide the directional growth and migration in various cell types. Furthermore, CNTF was encapsulated into PEGylated mesoporous silica nanoparticles (PMSN-CNTF NPs) for sustained release, reducing PC12 cell apoptosis in inflammatory conditions. Notably, in situ implantation of OF-Ce/Exo microtubules, coupled with intravitreal injection of PMSN-CNTF NPs, significantly promoted axonal regeneration and alleviated RGC death in a rat optic crush model, highlighting their potential for treating TON.
研究领域:
神经科学
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生物材料
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纳米医学
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再生医学
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药物递送系统
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神经创伤
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
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IF 5.2
Chenchen Zhu,Shuimiao Wang,Doudou Wang,Mengxia Hua,Sen Lin,Baoshan Huang,Shengjin Xiang,Kaihui Nan
Ciliary neurotrophic factor (CNTF) shows potential for stimulating axon regeneration of retinal ganglion cells (RGCs), whereas unordered regeneration of axons does not have any biological significance. Given the chemotaxis characteristics of RGCs, materials with gradient CNTF distribution can chemically stimulate axon extension based on the CNTF concentration gradient. Therefore, a novel nano-micro-macro multiple-nested hydrogel with gradient CNTF distribution was developed in this study to induce directional axonal outgrowth of RGCs. The CNTF and magnetic nanoparticles (MNPs) were co-loaded into gelatin microspheres (CNTF& [email protected] ), and subsequently suspended in a gelatin methacryloyl (GelMA) solution (viscous). Using a magnet, the CNTF& [email protected] were moved from the far-magnet side toward the near-magnet side forming gradient CNTF& [email protected] distribution inside the GelMA solution. The GelMA was then cross-linked via ultraviolet (365 nm) to form a hydrogel with gradient CNTF distribution. This hydrogel was further applied as the matrix for retinal explant culturing. The results showed that the number of axons in the segments of 200–300 µm and > 300 µm was 10.21 times and 15.02 times of those in the Gradient than those in the Without Gradient. The axons area distribution was 3.28 times and 13.41 times, respectively. 86.1% of the axons area in the Gradient were distributed in the segments > 200 µm, whereas only 56.27% in the Without Gradient. The results suggested that the hydrogel-matrix with gradient CNTF distribution could intensely induce directional axonal extension of RGCs in the retinal explant. The present study provides a new method for CNTF distribution, which could induce directional axonal regeneration of RGCs, and in turn have potential application in optic nerve injury repair to some extent.
研究领域:
神经科学
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生物材料
·
组织工程
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再生医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）