EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2025
·
IF 4.3
Fangming Liang,Yue Wang,Ning Li,YuBo Liu,Yuan Gao,Yinan Song,Zhenzhen Zhao,Yongjun Wang,Hongzhuo Liu
The treatment of posterior uveitis remains challenging due to the need for long-term medication and the limited efficacy of current therapies. In this study, we developed an injectable rapamycin-based nanoparticle formulation designed to extend intraocular residence time and enhance retinal penetration, thereby improving therapeutic outcomes. The nanoparticles were formed via self-assembly of rapamycin conjugated with a hydrophobic alkyl chain, yielding uniformly spherical particles with an average diameter of approximately 90 nm. In vitro experiments confirmed that the formulation exhibited minimal cytotoxicity, potent anti-inflammatory effects, inhibition of endothelial cell migration, and efficient uptake by retinal pigment epithelial (RPE) cells. In vivo imaging demonstrated that the nanoparticles rapidly localized to the RPE layer of the posterior segment following intravitreal injection, in contrast to the free drug. Moreover, experimental autoimmune uveoretinitis (EAU) rats treated with nanoparticles exhibited a substantial alleviation of ocular inflammation and a concomitant reduction in the expression of inflammatory markers, including CD45, CD68, IBA-1, and IL-17.
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DOI
PubMed
高影响因子
Small
·
2026
·
IF 11.8
Shundong Cai,Mengdie Li,Jingbin Zhuang,Jinfa Ye,Songyi Wang,Jinglei Zhang,Mingyou Zhang,Qixuan Dai,Yun Han,Min Su,Wei Li,Gang Liu,Chengchao Chu
Uveitis poses a severe threat to vision and represents a critical clinical challenge. Conventional therapeutic approaches often exhibit limited efficacy in controlling disease progression and lack efficient mechanisms for managing localized oxidative stress. Given that molecular hydrogen (H 2 ) holds substantial promise for treating oxidative and inflammatory diseases via its selective antioxidant properties, we report a metal–organic framework (MOF) nanozyme-based hydrogen nanogenerator. This system integrates photocatalytic visible-light-triggered H 2 generation with multi-enzyme-like antioxidant functions for targeted uveitis management. The engineered Pt-embedded MOF nanozymes (Pt@MOF) concurrently catalyze hydrogen evolution under visible light and display superoxide dismutase- and catalase-like activities, achieving comprehensive scavenging of overproduced reactive oxygen species (ROS). Furthermore, camouflaging the nanozyme with M2 macrophage-derived cell membrane vesicles (CMVs) endows the nanoplatform with active inflammation-targeting ability, thereby enhancing the accumulation in inflamed ocular tissues. Following topical administration, this biomimetic nanomedicine successfully mitigates oxidative stress and suppresses pro-inflammatory cytokines both in vitro and in a rat model of acute uveitis. Overall, this study underscores the immense potential of integrating light-driven hydrogen therapy with nanozyme therapy, offering a highly effective strategy that could revolutionize future therapeutic interventions for inflammatory eye diseases.
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 28
·4402-4412
·
IF 5.047
Mengwei Zou,Rongrong Jin,Yanfei Hu,Ying Zhang,Haibo Wang,Gongyan Liu,Yu Nie,Yunbing Wang
Indomethacin (IND) is a nonsteroidal anti-inflammatory drug (NSAID), which is widely used to relieve inflammation. However, general eye drops cannot reach lesions efficiently due to the presence of complicated and special biological barriers in the eye. Repeated administration of this drug for chronic ophthalmic diseases also showed poor patient compliance. Herein, an in situ injectable thermo-sensitive hydrogel of indomethacin-conjugated polymer was fabricated to overcome these crucial problems. The poly(NIPAAm-co-MAA-co-HTI) (PNMHTI) hydrogel, composed of N-isopropylacrylamide (NIPAAm), methacrylic acid (MAA), and 2-hydroxylethyl methacrylate-g-poly(trimethylene carbonate)-indomethacin (HEMA-g-PTMC-IND) (HTI), was synthesized by radical polymerization of NIPAAm, MAA and HTI. According to the rheology investigation, the sol–gel conversion temperature of the hydrogels was around 33 °C, and the sol–gel transition occurred at physiological temperature (37 °C). The release of indomethacin from the injectable hydrogels was sustained for over 2 weeks in phosphate buffer saline with esterase due to the sustained biodegradable behavior by the hydrolytic cleavage of the residual PTMC chains. In addition, these hydrogels displayed excellent biocompatibility against mouse fibroblasts, reduced cytotoxicity for indomethacin and a significant anti-inflammatory effect against macrophages. Uveitis was successfully established in New Zealand rabbits, and the PNMHTI hydrogels were injected into the vitreous body. Histopathological examination of retinas confirmed the good biocompatablity and anti-inflammatory effects of PNMHTI hydrogels in vivo. Overall, the PNMHTI hydrogels reported herein offer an attractive biomaterial-centered treatment option for uveitis.
研究领域:
药学
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材料科学
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眼科学
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生物医学工程
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高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Xue Wu,Lianyi Yang,Qing Chen,Ruijin Ran,Jun Cao,Ming Zhang
Experimental autoimmune uveitis (EAU) is a widely used model for noninfectious uveitis (NIU), a sight-threatening autoimmune ocular disease. Although glucocorticoids remain the first-line therapy, their short half-life and frequent administration increase the risk of systemic and ocular side effects. Here, we report the development of microenvironment-responsive hydrogels with drug-loaded microspheres for sustained dexamethasone acetate release: dexamethasone acetateloaded microspheres (DAMS) and polyethylene glycol (PEG) hydrogel-encapsulated microspheres (DAMS@Gel). Poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated and subsequently embedded in pH-responsive and injectable hydrogel formed via Schiff base crosslinking. The materials were then thoroughly characterized.In vitro, both DAMS and DAMS@Gel showed excellent biocompatibility with retinal pigment epithelial (ARPE-19) cells, as confirmed by reactive oxygen species (ROS), apoptosis, cell cycle, and cytotoxicity assays. In vivo safety was verified through subconjunctival injection in rabbits. In the rat EAU model, intravitreal administration of DAMS and DAMS@Gel significantly alleviated ocular inflammation, as evidenced by ocular inflammatory symptom observations, fundus imaging, histopathological examination, and decreased glial activation. This study demonstrated that the DAMS and DAMS@Gel drug delivery systems were successfully established and exhibited sustained release properties and stable characteristics. In vitro and in vivo assays indicated that the biological materials had excellent biocompatibility. In addition, both of DAMS and DAMS@Gel exerted therapeutic effects on EAU model rats, and intraocular inflammation was markedly reduced. This research may provide a theoretical foundation for the treatment of uveitis with DAMS and DAMS@Gel.
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Fan Cao,Kun Liang,Wei-Wei Tang,Qin-Yu Ni,Zhi-Yu Ji,Chen-Kai Zha,Ya-Kun Wang,Zheng-Xuan Jiang,Shengping Hou,Li-Ming Tao,Xianwen Wang
Uveitis comprises a cluster of intraocular inflammatory disorders characterized by uncontrolled autoimmune responses and excessive oxidative stress leading to vision loss worldwide. In the present study, curcumin (CUR) was conjugated with polyvinylpyrrolidone (PVP) to form PVP-CUR nanoparticles with significantly elevated solubility and outstanding multiple radical scavenging abilities. In vitro studies revealed that PVP-CUR nanoparticles markedly mitigated oxidative stress and reduced apoptosis in a H 2 O 2 -induced human retinal pigment epithelial cell line (ARPE-19) and promoted phenotypic polarization from M1 to M2 in an LPS-induced human microglial cell line (HMC3). Further in vivo studies demonstrated the prominent therapeutic effects of PVP-CUR nanoparticles on experimental autoimmune uveitis (EAU), which relieved clinical and pathological progression, improved perfusion and tomographic manifestations of retinal vessels, and reduced blood–retinal barrier (BRB) leakage; these effects may be mediated by mitigating oxidative stress and attenuating macrophage/microglia-elicited inflammation. Notably, treatment with PVP-CUR nanoparticles was shown to regulate metabolite alterations in EAU rats, providing novel insights into the underlying mechanisms involved. Additionally, the PVP-CUR nanoparticles showed great biocompatibility in vivo . In summary, our study revealed that PVP-CUR nanoparticles may serve as effective and safe nanodrugs for treating uveitis and other oxidative stress- and inflammation-related diseases.
研究领域:
药理学
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纳米技术
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免疫学
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眼科学
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代谢组学
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PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Jinrun Chen,Yuqin Wu,Bofei Xu,Jiabei Hou,Yijing Li,Yuhan Hu,Yutuo Zhu,Wenqiao Zhang,Shuqi Feng,Huanting Jin,Yuchen Cheng,Yuanyuan Jin,Jianhong Zhou,Xingyi Li
Activation of retina-specific CD4 + T cells capable of breaking through the blood-retinal barrier (BRB) was significantly associated with the onset and progression of autoimmune uveitis (AU). Antigen-presenting cells (APCs) orchestrate this process by presenting retinal antigens to naïve CD4 + T cells and driving their differentiation into autoreactive CD4 + T cells. Here, we report an intestinal APCs-targeted strategy for treating AU based on orally administered nanoCEL (diameter: 37.06 ± 0.12 nm), a pH-responsive nanomedicine exhibiting a great gastric acid stability and a pH-responsive drug release behavior. After oral administration, nanoCEL effectively penetrates the intestinal mucus barrier and targets APCs in the intestine. Using an experimental autoimmune uveitis rat model, oral administration of nanoCEL (2 mg/kg) exhibits a superior therapeutic efficacy than free CEL treatment by suppressing the antigen-presenting ability of APCs and impairing pathogenic T cell differentiation. Additionally, nanoCEL medication protects the BRB from the damage of pathogenic T cells by the reduction of the infiltration of peripheral immune cells and the activation of retinal glial cells. Compared to free CEL, oral administration of nanoCEL remarkably enhances drug bioavailability and improves biosafety without apparent systemic toxicity. Thus, the proposed APC-targeted nanodrug delivery system might be a promising strategy to treat AU.
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PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Yuelan Wu,Wenbo Geng,Qinjin Dai,Wanyun Zhang,Yuxian Lai,Pei Zhang,Chunjiang Zhou,Yinuo Wang,Qingfeng Cao,Xiang Luo,Yujie Lai,Changwei Huang,Peizeng Yang
Autoimmune uveitis is a sight-threatening inflammatory disease in which the cGAS-STING signaling pathway exacerbates inflammation by recognizing excessive cell-free DNA (cfDNA). However, conventional cfDNA scavengers have limited blood-retinal barrier penetration, and monotherapies cannot control the complex inflammatory network. Herein, we developed a cationic poly(disulfide)-drug nanoplatform (LA/DexP), which self-assembled via salt bridge interactions and aggregation-induced polymerization between a guanidyl-functionalized lipoic acid derivative (LA) and dexamethasone phosphate (DexP). This platform is designed to synergistically inhibit the cGAS-STING pathway and achieve efficient intraocular drug delivery. LA/DexP functioned as an efficient scavenger of cfDNA through electrostatic interaction, thereby inhibiting cGAS-STING overactivation. Meanwhile, it leveraged thiol-disulfide exchange to enhance blood-retinal barrier penetration, achieving a 5.09-fold higher apparent permeability coefficient than free DexP, and exhibited ROS-responsive drug release. In an experimental autoimmune uveitis mouse model, LA/DexP treatment significantly reduced cfDNA levels and inhibited cGAS-STING signaling. It also downregulated pro-inflammatory cytokine expression, promoted macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, and rebalanced Th1/Th17-Treg cell subsets. These combined effects effectively inhibited uveitis severity. In summary, this study establishes a highly barrier-permeable nanoplatform that synergistically integrates drug delivery with cGAS-STING pathway inhibition, offering a promising therapeutic strategy for autoimmune uveitis.
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高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2025
·
IF 4.3
Mali Dai,Pengyuan Du,Yijing Li,Xiaiting Wang,Jinrun Chen,Hui Liu,Wenqiao Zhang,Jianhong Zhou,Xingyi Li,Yuqin Wang
Effective treatment of chronic posterior ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration requires improvements in targeted drug delivery strategies. This study introduces a novel injectable drug delivery system co-assembled with a peptide-based hydrogel and secukinumab (SEK), an IL-17A neutralising monoclonal antibody, targeting retinal pigmented epithelium (RPE) cells. Compared to a SEK solution, the SEK loaded hydrogel significantly enhanced the protein uptake (3.7 times higher) by RPE cells in an inflammatory state after 24 h of treatment and increased the drug concentration in retinal tissues during 20 d of treatment. A single intravitreal injection of the SEK loaded hydrogel effectively suppressed inflammation in a uveitis model. It also reduced the immunoreactivity of microglia and T helper 17 cells, preserved the integrity of the blood-retina barrier, mitigated retinal cell apoptosis, and facilitated the recovery of the retinal function. This delivery system comprising an antibody-drug co-assembled with a peptide-based hydrogel shows promising potential for targeting the retina and treating complex chronic posterior ocular diseases.
研究领域:
药学
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眼科学
·
生物材料学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Yutuo Zhu,Jianhong Zhou,Yuhan Hu,Hui Shi,Yiping Wu,Minmengqi Pan,Jinrun Chen,Lihua Mo,Zhishu Bao,Jia Qu,Xingyi Li,Yuqin Wang
Autoimmune uveitis induces a serious pathological and inflammatory response in the retina/choroid and results in vision impairment and blindness. Here, we report a minocycline (Mino) nanocomposite-loaded hydrogel offering a high drug payload and sustained drug release for the effective control of ocular inflammation via a single subcutaneous injection . In the presence of divalent cations ( i.e., Ca 2+ ), Mino was found to co-assemble with a phosphorylated peptide ( i.e., NapGFFpY) via electrostatic interaction and consequently generating Mino nanocomposite. The drug entrapment efficiency (EE) of the Mino nanocomposite varied from 29.93 ± 0.76% to 67.90 ± 6.57%, depending on different component concentrations. After incorporation into 30 wt% poly (D,L-lactide)-b-poly (ethylene glycol)-b-poly (D,L-lactide) (PDLLA-PEG-PDLLA) thermosensitive hydrogel, the resulting Mino nanocomposite-loaded hydrogel provided a sustained drug release over 21 days. In the experimental autoimmune uveitis (EAU) rat model, a single subcutaneous injection of the Mino nanocomposite-loaded hydrogel effectively alleviated ocular inflammation in a dose-dependent manner. As indicated by optical coherence tomography (OCT) and electroretinogram (ERG) measurements, the Mino nanocomposite-loaded hydrogel treatment not only remarkably reduced destruction of the retina by EAU, but also greatly rescued retinal functions. Moreover, the proposed Mino nanocomposite-loaded hydrogel exerted its therapeutic effect on EAU primarily through a significant reduction of the influx of leukocytes and Th17 cells as well as suppression of microglia activation and apoptosis in the retina. Overall, the proposed Mino nanocomposite-loaded hydrogel might be a promising strategy for the clinical management of EAU.
研究领域:
药剂学
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眼科学
·
免疫学
·
纳米医学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Zhongxing Chen,Mei Yang,Qing Wang,Jieyi Bai,Colm McAlinden,Eirini Skiadaresi,Jun Zhang,Luting Pan,Chenyang Mei,Zhenhai Zeng,Jinjin Yu,Yifan Feng,Zhengxuan Jiang,Wenjin Xu,Hang Xu,Xiuhong Ye,Huanhuan He,Qinmei Wang,Junjie Deng,Jinhai Huang
Uveitis is one of the most popular blind-causing eye diseases worldwide. Adalimumab (ADA) is used for the uveitis treatment through systemic or intravitreal injection at the expense of systemic side effects and increased medical risks. Although eye drops, a non-invasive topical treatment, could be a potential strategy to reduce side effects, it remains challenging to apply due to limited bioavailability mainly linked to poor retention time and permeation capacity for eye biological barriers. Here, we reported hydrogel eye drops composed of low-deacetylated chitosan and β-glycerophosphate as an ADA carrier and tested its toxicity, tolerability, intraocular permeability, and efficacy of non-invasive treatment for uveitis. It’s found the ADA-loaded hydrogel eye drops were more efficient than free ADA both in permeation rate and clinical efficacy for uveitis, Overall, this study provides a friendly non-invasive strategy to improve drug permeation rate and uveitis treatment efficacy, which may be valuable to clinically ophthalmic medication.
研究领域:
眼科
·
药剂学
·
药物递送系统
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Tang Weiwei,Huang Xiaomin,Yi Yun-Di,Cao Fan,Deng Manli,Fan Jiawei,Jiang Zheng-Xuan,Tao Li-Ming,Wang Xianwen,Shi Lei
Globally, uveitis is a collection of intraocular inflammatory disorders that affect mainly the uvea, resulting in irreversible blindness and a heavy socioeconomic burden. Excessive autoimmune inflammation and oxidative stress are major drivers that contribute to the initiation and progression of uveitis. Nevertheless, current therapeutic methods for uveitis are limited and are accompanied by several serious adverse effects. Recently, nanotechnology-based antioxidant strategies have provided novel options for the treatment of ocular diseases. Although curcumin (CUR) has prominent antioxidant capacity and reactive oxygen species (ROS) scavenging ability, its low bioavailability and undetermined mechanisms limit its extensive application. This investigation demonstrated that esterified hyaluronic acid-curcumin nanoparticles (HA-CUR NPs) with superior aqueous dispersion exhibited exceptional antioxidant enzyme mimetic activity, incorporating superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and free radical scavenging ability. Further in vitro and in vivo experimental results validated the protective function of HA-CUR NPs against oxidative stress-induced damage and inflammatory responses, attenuated pathological progression, relieved microvascular damage, and regulated fundus blood flow in retinal vascular networks. This may be attributable to the specific ability of HA-CUR NPs to target the CD44 receptor and activate the Keap1/Nrf2/HO-1 signaling pathway, suggesting a potential mechanism. In summary, this study revealed that HA-CUR NPs, which are composed of a natural product and biomacromolecules with outstanding artificial antioxidant enzyme activities, may be novel agents for effectively and safely treating uveitis and other ROS-related diseases.
研究领域:
药理学
·
免疫学
·
纳米医学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Jianhong Zhou,Xiangxiang Lin,Huiping Shang,Yutuo Zhu,Jinrun Chen,Mengyun Deng,Mali Dai,Dan Lin,Serhii Vakal,Yuqin Wang,Xingyi Li
Noninfectious (autoimmune and immune-mediated) uveitis is one of the primary diseases leading to blindness in the world. Due to the limitation of current first-line drugs for clinical uveitis, novel drugs and targets against uveitis are urgently needed. Ganciclovir (GCV), an FDA-approved antiviral drug, is often used to treat cytomegalovirus-induced retinitis in clinical patients. Recently, GCV was found to suppress neuroinflammation via targeting STING signaling because the STING pathway plays a pivotal role in autoimmune diseases. However, until now, the effect of GCV on non-infectious uveitis has never been explored. In this work, using the rat experimental autoimmune uveitis (EAU) model, we first found STING to be highly expressed in infiltrating cells (CD68 + , CD45 + , and CD4 + ) and retinal glial cells (Iba1 + and GFAP + ) of the immunized retina. More importantly, GCV treatment can significantly suppress the initiation and progression of EAU by inhibiting infiltration of Th17 and inflammatory cells into the retina. Mechanistically, we found that GCV could reverse the levels of pro-inflammatory factors (such as IL-1β) and chemokine-related factors (such as Cxcr3), possibly via targeting the STING pathway. The present results suggest that GCV may be considered as a novel therapeutic strategy against human uveitis.
研究领域:
免疫学
·
眼科学
·
药理学
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DOI
PubMed
高影响因子
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