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1.
Drug Dev Ind Pharm ; 49(9): 559-571, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37649422

RESUMEN

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disease that is associated with aging and is influenced by both genetic and environmental factors. Several studies and clinical trials have demonstrated that resveratrol (Res) and salidroside (Sal) are not only biologically safe but also influence AD biomarker trajectories. However, their clinical applications have been quite limited due to poor specificity, low solubility, and insufficient blood-brain barrier (BBB) penetration. Therefore, we developed a nano-drug delivery system in which Res and Sal were encapsulated in liposomes, which were surface-modified with ApoE (ApoE-Res/Sal-Lips) to compensate for these deficiencies. METHOD: In this study, ApoE-Res/Sal-Lips were prepared using a standard thin-film hydration method for liposomes. Then, cellular uptake of the loaded liposomes was assessed in vitro using fluorescent staining assays. A BBB model was constructed to investigate the capacity of the liposomes to cross the BBB in vitro, and the ability of liposomes to target the brain was observed by in vivo imaging. In addition, the neuroprotective effects of the different liposome formulations in APP/PS-1 mice were evaluated by measuring the changes in levels of oxidative, anti-inflammatory, and anti-apoptotic factors in the mice brains. RESULTS: In vitro, ApoE-Res/Sal-Lips increased the uptake of Res and Sal by bEnd.3 and N2a cells, enhanced BBB penetration, and improved transport efficiency. In vivo, the ApoE-Res/Sal-Lips were found to alleviate AD pathological symptoms, reduce learning and memory impairments, and improve brain function. CONCLUSION: ApoE-Res/Sal-Lips provide a new method for the treatment of AD.


Asunto(s)
Enfermedad de Alzheimer , Glucósidos , Enfermedades Neurodegenerativas , Fenoles , Ratones , Animales , Liposomas/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Resveratrol/farmacología , Barrera Hematoencefálica , Apolipoproteínas E/farmacología , Apolipoproteínas E/uso terapéutico
2.
Biochem Biophys Res Commun ; 601: 86-92, 2022 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-35231656

RESUMEN

RNA interference (RNAi)-based gene therapy that promotes anabolic bone formation is an effective approach for addressing osteoporosis. However, the selection of target gene and tissue-specific delivery systems has hindered the progression of this strategy. In this study, we identified casein kinase-2 interacting protein-1 encoding gene (Ckip-1), a negative regulator of bone formation, as an effective target of small interfering RNAs (siRNAs) for improving bone mass. Moreover, an impressive (DSS)6-Liposome (Lipos) nanoparticle system that could target the bone formation surface was synthesized to enhance the delivery of Ckip-1 siRNA to osteogenic lineage cells. The in vitro results confirmed that the (DSS)6-Lipos system could efficaciously improve the intracellular delivery of Ckip-1 siRNA without obvious cell toxicity. The in vivo application of the delivery system showed specific accumulation of siRNA in osteogenic cells located around the bone formation surface. Bone-related analysis indicated increased bone mass and improved bone microarchitecture in mice with ovariectomy-induced osteoporosis. Moreover, the biomechanical characteristics of the tibia were enhanced significantly, indicating increased resistance to fragile fracture induced by osteoporosis. Thus, (DSS)6-Lipos-Ckip-1 siRNA-based osteoanabolic therapy may be a promising option for the treatment of osteoporosis.


Asunto(s)
Osteogénesis , Osteoporosis , Animales , Proteínas Portadoras/metabolismo , Femenino , Liposomas , Ratones , Osteogénesis/genética , Osteoporosis/genética , Osteoporosis/metabolismo , Osteoporosis/terapia , Interferencia de ARN , ARN Interferente Pequeño/genética , Tratamiento con ARN de Interferencia
3.
J Liposome Res ; 31(2): 145-157, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32223361

RESUMEN

Tumour metastasis is a major cause of cancer treatment failure and death, and chemotherapy efficiency for gastric cancer patients is usually unsatisfactory due to tumour cell metastasis, poor targeting and serious adverse reactions. In this study, a kind of R8GD-modified epirubicin plus tetrandrine liposomes was prepared to enhance the antitumor efficiency via killing tumour cells, destroying tumour metastasis and inhibiting energy supply for tumour cells. In order to investigate the antitumour efficiency of the targeting liposomes, morphology observation, intracellular uptake, cytotoxic effects, and inhibition on tumour metastasis and energy supply were carried out in vitro, and tumour-bearing mice models were established to investigate the antitumour efficiency in vivo. In vitro results showed that R8GD-modified epirubicin plus tetrandrine liposomes with ideal physicochemical properties could kill the most tumour cells, inhibit tumour metastasis and cut-off energy supply for tumour cells. In vivo results exhibited that R8GD-modified epirubicin plus tetrandrine liposomes could enhance the accumulation in tumour site and display an obvious antitumor efficiency. Therefore, R8GD-modified epirubicin plus tetrandrine liposomes could be used as a potential therapy for treatment of gastric cancer.


Asunto(s)
Liposomas , Neoplasias Gástricas , Animales , Bencilisoquinolinas , Línea Celular Tumoral , Epirrubicina , Humanos , Ratones , Neoplasias Gástricas/tratamiento farmacológico
4.
J Liposome Res ; 31(2): 113-129, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32200703

RESUMEN

Non-small cell lung cancer (NSCLC) is a malignant cancer characterized by easy invasion, metastasis and poor prognosis, so that conventional chemotherapy cannot inhibit its invasion and metastasis. Doxorubicin (DOX), as a broad-spectrum antitumour drug, cannot be widely used in clinic because of its poor targeting, short half-life, strong toxicity and side effects. Therefore, the aim of our study is to construct a kind of PFV modified DOX plus schisandrin B liposomes to solve the above problems, and to explore its potential mechanism of inhibiting NSCLC invasion and metastasis. The antitumour efficiency of the targeting liposomes was carried out by cytotoxicity, heating ablation, wound healing, transwell, vasculogenic mimicry channels formation and metastasis-related protein tests in vitro. Pharmacodynamics were evaluated by tumour inhibition rate, HE staining and TUNEL test in vivo. The enhanced anti-metastatic mechanism of the targeting liposomes was attributed to the downregulation of vimentin, vascular endothelial growth factor, matrix metalloproteinase 9 and upregulation of E-cadherin. In conclusion, the PFV modified DOX plus schisandrin B liposomes prepared in this study provided a treatment strategy with high efficiency for NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Línea Celular Tumoral , Ciclooctanos , Doxorrubicina/farmacología , Transición Epitelial-Mesenquimal , Humanos , Lignanos , Liposomas , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos Policíclicos , Factor A de Crecimiento Endotelial Vascular
5.
J Liposome Res ; 31(3): 267-278, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32757676

RESUMEN

Osthole (Ost) is a coumarin compound and a potential drug for Alzheimer's disease (AD). However, the effectiveness of Ost is limited by solubility, bioavailability, and low permeability of the blood-brain barrier. In this study, we constructed Ost liposomes with modified CXCR4 on the surface (CXCR4-Ost-Lips), and investigated the intracellular distribution of liposomes in APP-SH-SY5Y cells. In addition, the neuroprotective effect of CXCR4-Ost-Lips was examined in vitro and in vivo. The results showed that CXCR4-Ost-Lips increased intracellular uptake by APP-SH-SY5Y cells and exerted a cytoprotective effect in vitro. The results of Ost brain distribution showed that CXCR4-Ost-Lips prolonged the cycle time of mice and increased the accumulation of Ost in the brain. In addition, CXCR4-Ost-Lips enhanced the effect of Ost in relieving AD-related pathologies. These results indicate that CXCR4-modified liposomes are a potential Ost carrier to treat AD.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Encéfalo , Cumarinas , Liposomas , Ratones
6.
Cancer Sci ; 111(2): 621-636, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31777993

RESUMEN

Chemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Péptidos de Penetración Celular/química , Diosgenina/análogos & derivados , Epirrubicina/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Células A549 , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diosgenina/administración & dosificación , Diosgenina/química , Diosgenina/farmacología , Epirrubicina/química , Epirrubicina/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Liposomas , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratas , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Drug Dev Ind Pharm ; 46(4): 621-634, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32162988

RESUMEN

As a malignant tumor, breast cancer is very prone to metastasis. Chemotherapy is one of the most common means for treating breast cancer. However, due to the serious metastasis and the poor targeting effect of traditional chemotherapeutic drugs, even after years of efforts, the therapeutic effect is still unsatisfied. Therefore, in this study, we constructed a kind of PFV modified epirubicin plus schisandrin B liposomes to solve the above disadvantages. In vitro experiments showed that the targeting liposomes with ideal physicochemical property could increase the cytotoxicity of MDA-MB-435S cells, destroy the formation of vasculogenic mimicry (VM), and inhibit tumor invasion and migration. Action mechanisms indicated that the inhibition of targeting liposomes on tumor metastasis was attributed to the regulation of the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), vimentin (VIM), and E-cadherin (E-cad). In vivo pharmacodynamic experiments showed that the targeting liposomes could significantly improve the antitumor effect in mice. H&E staining and TUNEL results showed that the targeting liposomes could promote the apoptosis of tumor cells. Hence, the PFV modified epirubicin plus schisandrin B liposomes constructed in this study provided a new therapeutic strategy for breast cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Epirrubicina/administración & dosificación , Lignanos/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos Policíclicos/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Embrión de Pollo , Membrana Corioalantoides , Ciclooctanos/administración & dosificación , Femenino , Humanos , Liposomas , Neoplasias Pulmonares/secundario , Ratones , Invasividad Neoplásica , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Drug Dev Ind Pharm ; 46(6): 916-930, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32362146

RESUMEN

Tumor invasion and metastasis are the nodus of anti-tumor. Epithelial cell-mesenchymal transition is widely regarded as one of the key steps in the invasion and metastasis of breast cancer. In this study, GGP modified daunorubicin plus dioscin liposomes are constructed and characterized. GGP modified daunorubicin plus dioscin liposome has suitable particle size, narrow PDI, zeta potential of about -5 mV, long cycle effect, and enhanced cell uptake due to surface modification of GGP making the liposome could enter the inside of the tumor to fully exert its anti-tumor effect. The results of in vitro experiments show that the liposome has superior killing effect on tumor cells and invasion. In vivo results indicate that the liposome prolongs the drug's prolonged time in the body and accumulates at the tumor site with little systemic toxicity. In short, the targeted liposome can effectively inhibit tumor invasion and may provide a new strategy for the treatment of invasive breast cancer.


Asunto(s)
Neoplasias de la Mama , Daunorrubicina/química , Diosgenina/análogos & derivados , Transición Epitelial-Mesenquimal , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Diosgenina/química , Humanos , Liposomas
9.
Biomater Sci ; 12(4): 1055-1068, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38226492

RESUMEN

Zinc alloys have emerged as promising materials for bone regeneration due to their moderate biodegradation rates. However, the blast release of Zn2+ from Zn alloy substrates affects cell behaviors and the subsequent osseointegration quality, retarding their early service performance. To address this issue, extracellular matrix-like hydroxyapatite (HA) nanorods were prepared on Zn-1Ca (ZN) by a combined hydrothermal treatment (HT). HA nanoclusters nucleate on the presetting ZnO layer and grow into nanorods with prolonged HT. HA nanorods protect the ZN substrate from serious corrosion and the corrosion rate is reduced by dozens of times compared with the bare ZN, resulting in a significantly decreased release of Zn2+ ions. The synergistic effect of HA nanorods and appropriate Zn2+ endow ZN implants with obviously improved behaviors of osteoblasts and endothelial cells (e.g. adhesion, proliferation and differentiation) in vitro and new bone formation in vivo. Our work opens up a promising avenue for Zn-based alloys to improve bone regeneration in clinics.


Asunto(s)
Materiales Biocompatibles Revestidos , Durapatita , Aleaciones , Corrosión , Células Endoteliales , Regeneración Ósea , Zinc , Ensayo de Materiales
10.
Int J Nanomedicine ; 19: 5193-5211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859958

RESUMEN

Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.


Asunto(s)
Apoptosis , Diosgenina , Ácido Hialurónico , Liposomas , Neoplasias Ováricas , Paclitaxel , Polietilenglicoles , Especies Reactivas de Oxígeno , Femenino , Liposomas/química , Liposomas/farmacocinética , Paclitaxel/farmacología , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Diosgenina/farmacología , Diosgenina/química , Diosgenina/farmacocinética , Diosgenina/administración & dosificación , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Línea Celular Tumoral , Polietilenglicoles/química , Animales , Especies Reactivas de Oxígeno/metabolismo , Humanos , Apoptosis/efectos de los fármacos , Sinergismo Farmacológico , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidiletanolaminas
11.
Int J Nanomedicine ; 19: 4217-4234, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38766660

RESUMEN

Introduction: Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that involves synovitis, cartilage destruction, and even joint damage. Traditional agents used for RA therapy remain unsatisfactory because of their low efficiency and obvious adverse effects. Therefore, we here established RA microenvironment-responsive targeted micelles that can respond to the increase in reactive oxygen species (ROS) levels in the joint and improve macrophage-specific targeting of loaded drugs. Methods: We here prepared ROS-responsive folate-modified curcumin micelles (TK-FA-Cur-Ms) in which thioketal (TK) was used as a ROS-responsive linker for modifying polyethylene glycol 5000 (PEG5000) on the micellar surface. When micelles were in the ROS-overexpressing inflammatory microenvironment, the PEG5000 hydration layer was shed, and the targeting ligand FA was exposed, thereby enhancing cellular uptake by macrophages through active targeting. The targeting, ROS sensitivity and anti-inflammatory properties of the micelles were assessed in vitro. Collagen-induced arthritis (CIA) rats model was utilized to investigate the targeting, expression of serum inflammatory factors and histology change of the articular cartilage by micelles in vivo. Results: TK-FA-Cur-Ms had a particle size of 90.07 ± 3.44 nm, which decreased to 78.87 ± 2.41 nm after incubation with H2O2. The micelles exhibited in vitro targeting of RAW264.7 cells and significantly inhibited inflammatory cytokine levels. Pharmacodynamic studies have revealed that TK-FA-Cur-Ms prolonged the drug circulation and exhibited augmented cartilage-protective and anti-inflammatory effects in vivo. Conclusion: The unique ROS-responsive targeted micelles with targeting, ROS sensitivity and anti-inflammatory properties were successfully prepared and may offer an effective therapeutic strategy against RA.


Asunto(s)
Artritis Reumatoide , Curcumina , Receptores de Folato Anclados a GPI , Micelas , Especies Reactivas de Oxígeno , Animales , Masculino , Ratones , Ratas , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacocinética , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Curcumina/administración & dosificación , Curcumina/química , Curcumina/farmacología , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Receptores de Folato Anclados a GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Tamaño de la Partícula , Polietilenglicoles/química , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo
12.
ACS Chem Neurosci ; 15(11): 2283-2295, 2024 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-38780450

RESUMEN

Oxidative stress and neuroinflammation in the aging brain are correlated with the development of neurodegenerative diseases, such as Alzheimer's disease (AD). The blood-brain barrier (BBB) poses a significant challenge to the effective delivery of therapeutics for AD. Prior research has demonstrated that menthol (Men) can augment the permeability of the BBB. Consequently, in the current study, we modified Men on the surface of liposomes to construct menthol-modified quercetin liposomes (Men-Qu-Lips), designed to cross the BBB and enhance quercetin (Qu) concentration in the brain for improved therapeutic efficacy. The experimental findings indicate that Men-Qu-Lips exhibited good encapsulation efficiency and stability, successfully crossed the BBB, improved oxidative stress and neuroinflammation in the brains of aged mice, protected neurons, and enhanced their learning and memory abilities.


Asunto(s)
Enfermedad de Alzheimer , Barrera Hematoencefálica , Encéfalo , Liposomas , Mentol , Quercetina , Quercetina/farmacología , Quercetina/administración & dosificación , Quercetina/química , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Ratones , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Mentol/farmacología , Mentol/administración & dosificación , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Masculino , Envejecimiento/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones Endogámicos C57BL
13.
ACS Biomater Sci Eng ; 10(7): 4437-4451, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38885017

RESUMEN

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage imbalance and disruption of cartilage extracellular matrix secretion. Identifying key genes that regulate cartilage differentiation and developing effective therapeutic strategies to restore their expression is crucial. In a previous study, we observed a significant correlation between the expression of the gene encoding casein kinase-2 interacting protein-1 (CKIP-1) in the cartilage of OA patients and OA severity scores, suggesting its potential involvement in OA development. To test this hypothesis, we synthesized a chondrocyte affinity plasmid, liposomes CKIP-1, to enhance CKIP-1 expression in chondrocytes. Our results demonstrated that injection of CAP-Lipos-CKIP-1 plasmid significantly improved OA joint destruction and restored joint motor function by enhancing cartilage extracellular matrix (ECM) secretion. Histological and cytological analyses confirmed that CKIP-1 maintains altered the phosphorylation of the signal transduction molecule SMAD2/3 of the transforming growth factor-ß (TGF-ß) pathway by promoting the phosphorylation of the 8T, 416S sit. Taken together, this work highlights a novel approach for the precise modulation of chondrocyte phenotype from an inflammatory to a noninflammatory state for the treatment of OA and may be broadly applicable to patients suffering from other arthritic diseases.


Asunto(s)
Condrocitos , Homeostasis , Liposomas , Osteoartritis , Condrocitos/metabolismo , Osteoartritis/terapia , Osteoartritis/patología , Osteoartritis/metabolismo , Liposomas/química , Humanos , Animales , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Masculino , Fosforilación , Cartílago Articular/metabolismo , Cartílago Articular/patología , Factor de Crecimiento Transformador beta/metabolismo , Matriz Extracelular/metabolismo , Proteína smad3/metabolismo , Proteína smad3/genética , Transducción de Señal , Plásmidos/genética , Nanopartículas/química , Nanopartículas/uso terapéutico , Proteína Smad2/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética
14.
Int J Biol Macromol ; 267(Pt 1): 131480, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38599427

RESUMEN

Bone regeneration remains a major clinical challenge, especially when infection necessitates prolonged antibiotic treatment. This study presents a membrane composed of self-assembled and interpenetrating GL13K, an antimicrobial peptide (AMP) derived from a salivary protein, in a collagen membrane for antimicrobial activity and enhanced bone regeneration. Commercially available collagen membranes were immersed in GL13K solution, and self-assembly was initiated by raising the solution pH to synthesize the multifunctional membrane called COL-GL. COL-GL was composed of interpenetrating large collagen fibers and short GL13K nanofibrils, which increased hydrophobicity, reduced biodegradation from collagenase, and stiffened the matrix compared to control collagen membranes. Incorporation of GL13K led to antimicrobial and anti-fouling activity against early oral surface colonizer Streptococcus gordonii while not affecting fibroblast cytocompatibility or pre-osteoblast osteogenic differentiation. GL13K in solution also reduced macrophage inflammatory cytokine expression and increased pro-healing cytokine expression. Bone formation in a rat calvarial model was accelerated at eight weeks with COL-GL compared to the gold-standard collagen membrane based on microcomputed tomography and histology. Interpenetration of GL13K within collagen sidesteps challenges with antimicrobial coatings on bone regeneration scaffolds while increasing bone regeneration. This strength makes COL-GL a promising approach to reduce post-surgical infections and aid bone regeneration in dental and orthopedic applications. STATEMENT OF SIGNIFICANCE: The COL-GL membrane, incorporating the antimicrobial peptide GL13K within a collagen membrane, signifies a noteworthy breakthrough in bone regeneration strategies for dental and orthopedic applications. By integrating self-assembled GL13K nanofibers into the membrane, this study successfully addresses the challenges associated with antimicrobial coatings, exhibiting improved antimicrobial and anti-fouling activity while preserving compatibility with fibroblasts and pre-osteoblasts. The accelerated bone formation observed in a rat calvarial model emphasizes the potential of this innovative approach to minimize post-surgical infections and enhance bone regeneration outcomes. As a promising alternative for future therapeutic interventions, this material tackles the clinical challenges of extended antibiotic treatments and antibiotic resistance in bone regeneration scenarios.


Asunto(s)
Péptidos Antimicrobianos , Regeneración Ósea , Colágeno , Membranas Artificiales , Nanofibras , Regeneración Ósea/efectos de los fármacos , Animales , Ratas , Nanofibras/química , Colágeno/química , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Osteogénesis/efectos de los fármacos , Ratones , Osteoblastos/efectos de los fármacos , Streptococcus gordonii/efectos de los fármacos , Masculino , Ratas Sprague-Dawley , Fibroblastos/efectos de los fármacos
15.
J Oral Maxillofac Surg ; 71(4): 682-8, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23298803

RESUMEN

PURPOSE: This study aimed to investigate the effects of an expandable implant (EI) in ovariectomized sheep. METHODS: The EI and taper implant (control group) were produced and placed in mandibles of ovariectomized sheep. Twelve weeks after implantation, resonance frequency analysis, biomechanical tests, histomorphometry, and micro-computed tomography were applied to detect the osseointegration in the 2 groups. RESULTS: The implant stability quotient values, maximal pullout forces, and bone-implant contact (BIC) were 60.3 ± 7.9, 511.0 ± 18.7 N, and 53.14% ± 4.56%, respectively, in the EI group and 58.3 ± 8.9, 394.5 ± 54.5 N, and 46.85% ± 5.04%, respectively, in the control group. There was no significant difference between the 2 groups in implant stability quotient values (P > .05); however, in the EI group the maximal pullout force and BIC were increased significantly (P < .05 and P < .01, respectively). Micro-computed tomography analysis showed that the bone volume/total volume ratio and trabecular number increased significantly (P < .01) and trabecular separation decreased significantly (P < .05) in the EI group. CONCLUSIONS: EI could improve osseointegration in osteoporosis after 12 weeks of implantation by increasing BIC around the implant and by supplying an extra osseointegration surface.


Asunto(s)
Implantación Dental Endoósea/métodos , Implantes Dentales , Diseño de Prótesis Dental , Oseointegración , Animales , Densidad Ósea , Diseño Asistido por Computadora , Retención de Prótesis Dentales , Análisis del Estrés Dental , Femenino , Mandíbula/cirugía , Osteoporosis/rehabilitación , Ovariectomía , Oveja Doméstica , Microtomografía por Rayos X
16.
Arch Orthop Trauma Surg ; 133(3): 295-301, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23274779

RESUMEN

PURPOSE: To evaluate effectiveness of carboxymethylcellulose/polyethylene oxide (CMC/PEO) gel in improving clinical outcomes after the first-time lumbar discectomy. METHOD: Ninety-three patients with herniated lumbar disc at L4-L5 or L5-S1 were enrolled and randomized into two groups: CMC/PEO gel treatment group and control group. All the patients underwent laminotomy and discectomy by posterior approach. The preoperative and postoperative Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) scores for lower-back pain and leg pain were analyzed and compared between two groups at 30- and 60-day time points. RESULTS: No patient presented with any clinically measurable adverse event during surgery. There were no significant differences between the treated group and the control group on the preoperative ODI and VAS scores. In general, the ODI and VAS scores decreased in both groups at all the time points. At the 30-day time point, the VAS scores for back pain and leg pain and the ODI scores in treatment group were lower by 9.9 % (P = 0.0302), 27.0 % (P = 0.0002) and 16.3 % (P = 0.0007) than those in control group. And at the 60-day time point, the ODI and VAS scores further decreased in both groups. The VAS scores for leg pain in treatment group were lower by 4.5 % than that in the control group (P = 0.0149). However, no significant difference was detected between two groups on the ODI and VAS scores for back pain. CONCLUSIONS: The results demonstrated that CMC/PEO gel is effective in reducing posterior dural adhesions in the spine with no apparent safety issues. It can improve patients' postoperative clinical outcome.


Asunto(s)
Antiinflamatorios/administración & dosificación , Carboximetilcelulosa de Sodio/administración & dosificación , Discectomía/efectos adversos , Desplazamiento del Disco Intervertebral/cirugía , Polietilenglicoles/administración & dosificación , Adherencias Tisulares/prevención & control , Adulto , Espacio Epidural , Femenino , Geles/administración & dosificación , Humanos , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Método Simple Ciego , Adherencias Tisulares/etiología
17.
J Control Release ; 363: 657-669, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37832724

RESUMEN

Peri-implantitis induced by infection leads to gingival recession, alveolar resorption and eventual dental implant failure. So, antibiosis and biosealing of abutments as well as osseointegration of roots need to be projected seriously during the whole service lifespan of dental implants. In this work, a multipurpose photothermal therapy strategy based on Si/P/F doped TiO2 matrix is proposed to address the above issues. This TiO2 matrix not only has outstanding photothermal response, but also triggers the release of F ions under near-infrared (NIR) light irradiation. Local hyperthermia assisted with the released F ions reduces adenosine triphosphate (ATP) synthesis of staphylococcus aureus (S. aureus), increases bacterial membrane permeability, and induces abundant of reactive oxygen species, resulting in the oxidation of cellular components and eventual death of bacteria. Furthermore, the synergic action of mild photothermal stimulation and Si/P/F ions of TiO2 matrix up-regulates gingival epithelial cells behavior (e.g., hemidesmosome formation) and osteoblasts response in vitro. In an infected model, this TiO2 matrix obviously eliminates bacteria, reduces inflammatory response, improves epithelial sealing and osseointegration, and reduces alveolar resorption by regulating NIR irradiation.


Asunto(s)
Pérdida de Hueso Alveolar , Humanos , Fluoruros , Staphylococcus aureus , Antibiosis , Regeneración Ósea , Titanio , Antibacterianos/farmacología
18.
Macromol Biosci ; 23(4): e2200436, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36617598

RESUMEN

The stress shielding effect caused by traditional metal implants is circumvented by using polyetheretherketone (PEEK), due to its excellent mechanical properties; however, the biologically inert nature of PEEK limits its application. Endowing PEEK with biological activity to promote osseointegration would increase its applicability for bone replacement implants. A biomimetic study is performed, inspired by mineralized collagen fiber bundles that contact bone marrow mesenchymal stem cells (BMMSCs) on the native trabecular bone surface. The PEEK surface (P) is first sulfonated with sulfuric acid to form a porous network structure (sP). The surface is then encapsulated with amorphous hydroxyapatite (HA) by magnetron sputtering to form a biomimetic scaffold that resembles mineralized collagen fiber bundles (sPHA). Amorphous HA simulates the composition of osteogenic regions in vivo and exhibits strong biological activity. In vitro results show that more favorable cell adhesion and osteogenic differentiation can be attained with the novelsurface of sPHA than with SP. The results of in vivo experiments show that sPHA exhibits osteoinductive and osteoconductive activity and facilitates bone formation and osseointegration. Therefore, the surface modification strategy can significantly improve the biological activity of PEEK, facilitate effective osseointegration, and inspire further bionic modification of other inert polymers similar to PEEK.


Asunto(s)
Oseointegración , Osteogénesis , Biomimética , Polietilenglicoles/farmacología , Polietilenglicoles/química , Cetonas/farmacología , Cetonas/química , Durapatita/farmacología , Durapatita/química , Colágeno , Propiedades de Superficie
19.
Adv Healthc Mater ; 12(8): e2202270, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36457271

RESUMEN

Bacterial infection is one of the most frequent wound complications and has become a major public health concern. Increasing resistance to antibiotics has been noted with these agents broadly used in wound management. It is an urgent demand to develop alternative antibacterial strategies with a reduced chance of resistance. Herein, a Nepenthes-mimicking nanosheet array of MoS2 on carbon fibers (CF-MoS2 ) is proposed to achieve dual bactericidal activities. First, the sharp edges of synthesized surfaces are capable of inducing physical disruption of cell membranes, demonstrating mechanical antibacterial activity like their natural counterparts. Second, in the presence of near-infrared light, bioinspired CF-MoS2 nanosheets are able to cause the death of damaged bacteria owing to their inherent photothermal properties. Such dual-functional modes endow the surfaces with nearly 100% killing efficiency for highly concentrated Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, their potential to be applied as wound dressings for photothermal treatment of infectious wounds is also investigated in vivo. Bioinspired CF-MoS2 dressings show advantages of synergistic disinfection and efficient promotion of wound regeneration. It is foreseen that this high-performance and multifunctional CF-MoS2 could afford a feasible broad-spectrum treatment for non-antibiotic disinfection.


Asunto(s)
Escherichia coli , Infecciones Estafilocócicas , Humanos , Fibra de Carbono , Molibdeno/farmacología , Desinfección , Staphylococcus aureus , Antibacterianos/farmacología
20.
J Drug Target ; 31(6): 634-645, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37203195

RESUMEN

The blood-brain barrier (BBB) is a barrier that maintains brain homeostasis, but it is also one of the major problems that must be overcome in the development of Alzheimer's disease (AD) drugs. To solve this problem, Salidroside (Sal) and Icariin (Ica), drugs with neuroprotective effects were loaded into liposomes, and the targeting molecule Angiopep-2 was modified on the surface of liposomes (Ang-Sal/Ica-Lip), so that the constructed nano-drug delivery system could effectively cross the BBB and exert anti-AD effects. The prepared liposomes exhibited ideal physicochemical properties. In vitro and in vivo targeting studies showed that Ang-Sal/Ica liposome could cross the BBB to increase drug accumulation in the brain, and increase the uptake of N2a cells and bEnd.3 cells. The pharmacodynamic analysis in vivo showed that Ang-Sal/Ica liposome could reverse neuronal and synaptic damage, inhibit neuroinflammation and oxidative stress and improve learning and cognitive function. Therefore, Ang-Sal/Ica liposome may be a promising therapeutic strategy for mitigating AD-related symptoms.


Asunto(s)
Enfermedad de Alzheimer , Liposomas , Ratones , Animales , Liposomas/química , Enfermedad de Alzheimer/tratamiento farmacológico , Células Endoteliales , Encéfalo , Barrera Hematoencefálica
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