Journal of Materials Chemistry B
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2020
·Vol. 8
·期 13
·2573-2588
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IF 5.344
Jintian Chen,Hui Wang,Liling Mei,Bei Wang,Ying Huang,Guilan Quan,Chao Lu,Tingting Peng,Xin Pan,Chuanbin Wu
A deep partial thickness (DPT) burn injury refers to burn damage involving the epidermis and major dermis, whose prognosis depends greatly on wound management. Lack of effective management can lead to an elongated healing process and aggravated scar formation, which can severely disturb patients, both physically and mentally. A dressing with good water absorption and moderate mechanical properties is crucial for healing promotion, and the prevention of scar formation is highly desirable. In this project, a hyaluronic acid combined lyotropic liquid crystal based spray dressing (HLCSD) loaded with the anti-fibrotic drug pirfenidone (PFD) has been designed. HLCSD is expected to achieve the goals of both wound healing promotion and scar prophylaxis. Its water absorption capacity, mechanical properties, drug release behavior and phase transition are fully evaluated. HLCSD possesses low viscosity for spray administration and high levels of water absorption for exudate absorption. An in situ gel composed of self-assembled lattice nanostructures provides excellent mechanical protection to promote the healing process and steady PFD release to exert a scar prophylaxis effect. The benefit of HLCSD on the wound healing rate is verified in vivo. In the DPT burn wound model we established, HLCSD also exhibits excellent healing promotion effects, and PFD-loaded HLCSD shows scar prophylaxis effects and displays an ideal prognosis, with skin as smooth as healthy skin. The healing promotion of HLCSD is considered to be related to the alleviation of inflammation, with an obviously shortened inflammation phase, with contributions from water management, mechanical protection and anti-inflammation by HLCSD. The scar prophylaxis of PFD-loaded HLCSD is proven to be related to the regulation of collagen synthesis and degradation, involving key cytokines like TGF-β and MMP-1. Taken together, the PFD-loaded HLCSD with healing promotion and scar prophylaxis offers significant promise as a spray dressing for DPT burn injuries.
研究领域:
药剂学
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生物医学工程
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伤口愈合
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烧伤治疗
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药物递送系统
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Kaili Wang,Hao Chen,Si Qin,Shuhui Chen,Qian Zhang,Jiali Chen,Donghua Di,Guangyue Su,Yue Yuan
Hepatic fibrosis, as a destructive liver disease, occurs due to activated hepatic stellate cells (HSCs) producing excessive extracellular matrix deposition. If left untreated, it could further deteriorate into cirrhosis and hepatoma with high morbidity and mortality. Currently, to break the dilemma of poor targeting efficiency on HSCs and limited effect of monotherapy, it is urgent to explore a precise and efficient treatment against liver fibrosis. In the present work, a novel multifunctional nanoplatform based on vitamin A (VA) modified zeolitic imidazolate framework-8 (ZIF-8) nanoparticles was designed for co-delivery of chemical drug (Pirfenidone) and genetic drug (TGF-β 1 siRNA) to achieve HSCs targeting mediated synergistic chemo-gene therapy against liver fibrosis. With the large specific surface area and acid-responsive degradation characteristics, ZIF-8 nanoparticles have great advantages to achieve high loading efficiency of Pirfenidone and enable acid-reactive drug release. After complexing siRNA, the prepared chemo-gene drug co-delivered nanocomplex (GP@ZIF-VL) proved excellent serum stability and effectively protected siRNA from degradation. Importantly, in vitro cell uptake and in vivo biodistribution demonstrated that VA functionalization markedly enhanced the delivery efficiency of GP@ZIF-VL nanocomplex into HSCs. As expected, GP@ZIF-VL significantly reduced extracellular matrix deposition and ameliorated hepatic fibrosis, as evidenced by decreased levels of liver enzymes in serum and a reduction in the hydroxyproline content in liver tissue. Therefore, GP@ZIF-VL nanocomplex displayed a bright future on the treatment of liver fibrosis with HSCs-targeting mediated chemo-gene synergetic therapy.
研究领域:
药学
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纳米技术
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分子生物学
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肝病学
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PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Feng Gao,Jianrong Wu,Shiwei Niu,Ting Sun,Fan Li,Yun Bai,Lifang Jin,Lizhou Lin,Qiusheng Shi,Li-Min Zhu,Lianfang Du
The dense extracellular matrix (ECM) and hypovascular networks were often found in solid pancreatic tumors form an impenetrable barrier, leading to limited uptake of chemotherapeutics and thus undesirable treatment outcomes. Methods : A biodegradable nanoplatform based on hollow mesoporous organosilica nanoparticle (HMON) was designed as an effective delivery system for pirfenidone (PFD) to overcome the challenges in pancreatic tumor treatment. By varying pH producing a mildly acidic environment to emulate tumor cells, results in cleavage of the acetal bond between HMON nanoparticle and gating molecular, gemcitabine (Gem), enabling its controlled release. Results : The in vitro and in vivo immunocytochemistry evaluations demonstrated an excellent ECM regulation efficacy of the nanoplatform and therefore the improved penetration of drug into the cells. The technique employed was especially enhanced when mediated with ultrasound target microbubble destruction (UTMD). Evaluations culminated with pancreatic cancer bearing mice and demonstrated therapeutic efficacy, good biodegradability, and negligible systemic toxicity. Conclusion : the designed Gem gated biodegradable nanosystem is expected to provide an alternative way of improving antitumor efficacy by down-regulation of ECM levels and offers a passive-targeted therapy for pancreatic cancer treatment.
研究领域:
纳米技术
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药学
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肿瘤学
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生物医学工程
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癌症治疗
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PubMed
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 9
·1374
·
IF 5.7
Qinxiu Zhang,Shouwei Sun,Miaomiao Lu,Runxin Qin,Junxuan Ren,Lianjie Yao,Dianlong Jia,Jinjie Chang,Xiaohong Chu,Rui Wang,Fang Liu,Jun Li
Background:Pulmonary fibrosis (PF) is a progressive lung disease with limited therapies. Oral Pirfenidone (PFD), an approved anti-fibrotic, shows poor lung bioavailability and significant toxicity. S-Allylmercapto-N-acetylcysteine (ASSNAC) has been demonstrated to possess significant anti-inflammatory and antioxidant properties.Methods:In this study, dry powder inhaler formulations (DPIs) co-encapsulating ASSNAC and PFD in liposomes are reported. The formulation was prepared via spray freeze-drying (SFD) using L-leucine as both a cryoprotectant and a surface morphology modifier. The interfacial enrichment of L-leucine during atomization and freezing created a hydrophobic, corrugated surface that lowered particle surface energy, prevented liquid/solid bridge formation, and reduced hygroscopicity.Results:The resulting liposomal powders exhibited optimal aerosol performance: fine particle fraction (FPF) of 61.08% ± 2.45% and mass median aerodynamic diameter (MMAD) of 2.22 ± 0.11 µm. Cellular studies demonstrated that dual-loaded liposomes were efficiently taken up by Beas-2B and HFL-1 cells, with no cytotoxicity (cell viability > 90%) and negligible hemolysis. In the TGF-β1-induced in vitro fibrosis model, the combined treatment exerted prominent therapeutic effects. This regimen preserved normal epithelial morphology, accelerated wound repair, suppressed fibroblast invasiveness, and lowered the expression levels of Collagen I, Collagen III, and α-SMA. In bleomycin-induced pulmonary fibrosis rats, inhaled ASSNAC + PFD liposomal powder markedly relieved lung tissue injury and collagen accumulation. It restored redox balance and lowered pulmonary TGF-β1, hydroxyproline and collagen III levels. The formulation blocked TGF-β1 signaling and fibrotic gene expression.Conclusions:Pulmonary administration avoids oral pirfenidone-induced liver and stomach toxicity. Collectively, the ASSNAC + PFD co-encapsulated liposomal dry powder produced by SFD represents a safe and efficacious therapeutic strategy for PF.
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