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1.
Ren Fail ; 45(1): 2149412, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36636989

RESUMO

Clodronate liposomes are bisphosphonates encapsulated by liposomes that are known to induce macrophage depletion in vivo. In a previous study, clodronate liposomes improved renal ischemia/reperfusion (I/R) injury in mice, which may be due to effects on macrophage phenotypes. However, how inflammatory cytokines secretion participates is unknown. In this study, we investigated the effect of macrophages in the I/R kidney by depleting macrophages with clodronate liposomes and changing inflammatory cytokines. C57BL/6 mice underwent I/R injury with or without clodronate liposomes administration on Days 5 and 15. Tubular injury, collagen deposition, and fibrosis were detected and analyzed by histological staining, immunocytochemistry (IHC), flow cytometry (FACS), and reverse transcription-polymerase chain reaction (RT-PCR). Inflammatory cytokines were detected and analyzed by Western blotting and RT-PCR. We found that clodronate liposomes alleviated renal fibrosis and tissue damage on both Days 5 and 15. KIM-1, IL-10, and TGF-ß were reduced significantly in the clodronate liposomes treatment group. However, TNF-α was not different between the clodronate liposomes treatment group and the phosphate-buffered saline treatment group on either Day 5 or Day 15. Thus, clodronate liposomes can alleviate renal fibrosis and tissue damage and reduce the inflammatory cytokines IL-10 and TGF-ß, suggesting that clodronate liposomes alleviate renal fibrosis may because of M1/M2 polarization.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Traumatismo por Reperfusão , Camundongos , Animais , Ácido Clodrônico/farmacologia , Lipossomos/farmacologia , Interleucina-10/farmacologia , Camundongos Endogâmicos C57BL , Macrófagos/patologia , Citocinas , Fibrose , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Insuficiência Renal Crônica/complicações , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Fator de Crescimento Transformador beta
2.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4666-4673, 2021 Sep.
Artigo em Zh | MEDLINE | ID: mdl-34581074

RESUMO

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.


Assuntos
Materiais Biocompatíveis , Orchidaceae , Sistemas de Liberação de Medicamentos , Polissacarídeos , Cicatrização
3.
AAPS PharmSciTech ; 21(2): 66, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932983

RESUMO

The purpose of this study was to investigate the potential of Bletilla striata polysaccharide (BSP, a natural glucomannan material) for the development of a gastroretentive drug delivery system for the first time. Novel BSP-based porous wafer was prepared for levofloxacin hydrochloride (LFH) delivery by combining floating, swelling, and mucoadhesion mechanisms. The influences of BSP and ethyl cellulose (EC) on drug release and mucoadhesive strength were studied by 32 factorial design. The optimized matrix was coated with polycaprolactone (PCL) electrospun membrane by electrospinning and heat treatment technology. The optimized formula (F6, coated) exhibited Q4 h of 41.20 ± 1.90%, Q8 h of 76.49 ± 1.69%, and mucoadhesive strength of 86.11 ± 1.33 gf, and its drug release profile most closely resembled the Korsmeyer-Peppas model with anomalous diffusion driving mechanism. F6 (coated) also presented excellent buoyancy, preferred swelling characteristic due to the porous structure formed by freeze-drying. Meanwhile, the internal morphology, physical state, drug-excipient compatibility, and thermal behavior were recorded. The negligible cytotoxicity of F6 (coated) was observed in human gastric epithelial cell cultures. In the in vitro antimicrobial experiment, the prepared wafer exhibited obvious bacterial inhibition zone, and due to its longer gastric retention, the wafer also performed a more effective Helicobacter pylori clearance than free LFH in vivo. Graphical abstract.


Assuntos
Sistemas de Liberação de Medicamentos , Mucosa Gástrica/metabolismo , Mananas/química , Orchidaceae/química , Poliésteres/química , Células Cultivadas , Celulose/análogos & derivados , Celulose/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos
4.
Int J Biol Macromol ; 263(Pt 2): 130282, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423901

RESUMO

Aiming at green and friendly environmental protection, polyvinyl alcohol/sodium alginate/chitosan (PSCS) double network hydrogel was successfully prepared through diffusing the high molecular weight chitosan into PVA/sodium alginate (PS) hydrogel without any other toxic reagents. The polyanion hydrogels could be significantly enhanced by immersing the polyanion hydrogel in high molecular weight chitosan solution without requiring specific structure. The PSCS hydrogel had a compact and rough surface structure with the smaller porosities and larger crystallization degree compared with polyvinyl alcohol/sodium alginate hydrogels and polyvinyl alcohol/sodium alginate/Ca2+ (PSCa) hydrogels. The PSCS hydrogel possessed excellent hydrolysis resistance, the significant pH-sensitive and salt-sensitive swelling. In addition, the flexibility, Young's modulus and mechanical properties of PSCS hydrogel can be adjusted through the changing the content of sodium alginate. Moreover, PS, PSCa and PSCS had electric conductivity, and PSCS showed twice the conductivity compared to PS hydrogel. Based on differences of swelling ratio, a PSCS bilayer hydrogel was designed and showed excellent pH-driven deformation ability. The PSCS hydrogel is expected to expand the application of hydrogels in conditions involving stimulus response, and might serve as a promising intelligent actuators or soft robots.


Assuntos
Quitosana , Polieletrólitos , Quitosana/química , Álcool de Polivinil/química , Hidrogéis/química , Alginatos/química , Concentração de Íons de Hidrogênio , Condutividade Elétrica
5.
Int J Biol Macromol ; 234: 123693, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36806778

RESUMO

In this study, a novel nanofiber material with Polylactic acid (PLA), natural plant polysaccharides-Bletilla striata polysaccharide (BSP) and Rosmarinic acid (RA) as the raw materials to facilitate wound healing was well prepared through coaxial electrospinning. The morphology of RA-BSP-PVA@PLA nanofibers was characterized through scanning electron microscopy (SEM), and the successful formation of core-shell structure was verified under confocal laser microscopy (CLSM) and Fourier transform infrared spectroscopy (FTIR). RA-BSP-PVA@PLA exhibited suitable air permeability for wound healing, as indicated by the result of the water vapor permeability (WVTR) study. The results of tension test results indicated the RA-BSP-PVA@PLA nanofiber exhibited excellent flexibility and better accommodates wounds. Moreover, the biocompatibility of RA-BSP-PVA@PLA was examined through MTT assay. Lastly, RA-BSP-PVA@PLA nanofibers can induce wound tissue growth, as verified by the rat dorsal skin wound models and tissue sections. Furthermore, RA-BSP-PVA@PLA can facilitate the proliferation and transformation of early wound macrophages, and down-regulate MPO+ expression of on the wound, thus facilitating wound healing, as confirmed by the result of immunohistochemical. Thus, RA-BSP-PVA@PLA nanofibers show great potential as wound dressings in wound healing.


Assuntos
Nanofibras , Orchidaceae , Ratos , Animais , Nanofibras/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Cicatrização , Poliésteres/química , Orchidaceae/química , Álcool de Polivinil/química , Ácido Rosmarínico
6.
ACS Appl Mater Interfaces ; 15(29): 34554-34569, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37462246

RESUMO

Nowadays, the combined use of chemotherapy and photodynamic therapy (PDT) remains the most popular strategy for cancer treatment with high theraprutic efficacy. However, targeted therapy with the on-demand release of drugs is what most clinical treatments lack, leading to heavy side effects. Herein, a new CD44-targeted and red-light-activatable nanosystem, Ru-HA@DOX nanoparticles (NPs), was developed by conjugating hydrophilic biodegradable hyaluronic acid (HA) and hydrophobic photoresponsive ruthenium (Ru) complexes, which could encapsulate the chemotherapeutic drug doxrubicin (DOX). Ru-HA@DOX NPs can selectively accumulate at the tumor through the enhanced permeability and retention (EPR) effect and CD44-mediated endocytosis, thus avoiding off-target toxicity during circulation. After 660 nm of irradiation at the tumor site, Ru-HA@DOX NPs, as a "photoactivatable bomb", was split via the photocleavable Ru-N coordination bond to fast release DOX and produce singlet oxygen (1O2) for PDT. In general, Ru-HA@DOX NPs retained its integrity before irradiation and possessed minimal cytotoxicity, while under red-light irradiation, Ru-HA@DOX NPs showed significant cytotoxicity due to the release of DOX and production of 1O2 at the tumor. Chemotherapy-PDT of Ru-HA@DOX NPs resulted in a significant inhibition of tumor growth in A549-tumor-bearing mice and reduced the cardiotoxicity of DOX. Therefore, this study offers a novel CD44-targeted drug-delivery system with on-demand drug release for synergistic chemotherapy-PDT.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Preparações Farmacêuticas , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/química , Polímeros/química , Fotoquimioterapia/métodos , Ácido Hialurônico/química , Linhagem Celular Tumoral
7.
Carbohydr Polym ; 273: 118557, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560968

RESUMO

A low-cost wound dressing with efficient sterilization and exhibiting long-term antimicrobial activity is required for the absence of antibiotics, particularly for the wound healing of patients with chronic wounds or long-term activities under low sanitary conditions (e.g., battlefield and poverty-stricken areas). Here, a dual dynamic crosslinking hydrogel was introduced. The hydrogel was supported by gallic acid grafted chitosan and oxidized Bletilla striata polysaccharide as the scaffold and formed by two types of dynamic crosslinking: Schiff base, pyrogallol-Fe3+. It exhibited its adhesion, self-healing, good biocompatibility, great intrinsic antibacterial, and near-infrared photothermal conversion activity. In addition, the use of two types of polysaccharides, and the existence of the photothermal effect, making the hydrogel has the functions of accelerating gelation, degradation on-demand, and rapid sterilization. In brief, such cost-effective multifunctional hydrogel could support wound healing in patients prone to bacterial infection, and it has a promising application in the care of infected wounds.


Assuntos
Hidrogéis/farmacologia , Terapia Fototérmica/métodos , Polissacarídeos/química , Adesivos Teciduais/farmacologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/terapia , Animais , Antibacterianos/farmacologia , Infecções Bacterianas/terapia , Bandagens , Quitosana/química , Hidrogéis/química , Masculino , Camundongos , Orchidaceae/química , Ratos , Ratos Sprague-Dawley , Bases de Schiff , Staphylococcus aureus/efeitos dos fármacos , Adesivos Teciduais/química
8.
Chin J Cancer ; 29(8): 768-73, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20663325

RESUMO

BACKGROUND AND OBJECTIVE: The primary submucous type of nasopharyngeal carcinoma (NPC) or the recurrent NPC in the parapharyngeal space is difficult to be diagnosed histologically by conventional biopsy because of the obstruction of the surrounding structures. This study was performed to evaluate the needle biopsy approach through the madibular area into the parapharyngeal space under the guidance of computed tomography (CT) for NPC. METHODS: Between July 6, 2005 and October 23, 2009, a total of 6 patients were enrolled into the study. Two patients with cervical lymph node metastasis were clinically suspicious of NPC according to their clinical manifestations. However, no cancer cell could be found by repeated nasopharyngeal biopsies followed by histologic examinations. The other 4 patients were diagnosed with recurrent NPCs by magnetic resonance imaging (MRI) or/and positron emission tomography (PET)-CT scan, showing tumors in the parapharyngeal spaces in 3 patients and enlarged retropharyngeal lymph node in 1 patient. The CT-guided puncture was performed through the mandibular skin and the cutting needle biopsy was taken at the parapharyngeal space focus. RESULTS: All the cutting needle biopsies of projected locations have been performed safely. Finally, all the 7 specimens met the requirement of pathologic diagnosis and the cases were all confirmed histologically to be NPCs. The main complication was mild ache at the puncture point. No blood vessel or nerve was injured and no patient needed special treatment. CONCLUSIONS: The CT-guided puncture biopsy of the parapharyngeal space through the mandibular area is simple and feasible. It can be an additional option for routine nasopharyngeal biopsy.


Assuntos
Biópsia por Agulha/métodos , Linfonodos/patologia , Neoplasias Nasofaríngeas/diagnóstico , Faringe/patologia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Mandíbula , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
9.
Biomaterials ; 230: 119666, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31831222

RESUMO

Various obstacles impede the chemotherapy efficiency of glioma in clinic, such as blood brain barrier (BBB) and blood brain tumor barrier (BBTB). Ligand-mediated polymeric micelles have shown great potential for improving the efficiency of glioma treatment. Herein, we developed a disulfide bond-conjugated prodrug polymer consisted of camptothecin (CPT) and polyethylene glycol (PEG) with further modification of iRGD peptide. The polymer of CPT-S-S-PEG-COOH could self-assemble into nanosized polymeric micelles with diameter around 100 nm, and loaded with photosensitizer IR780 for combination therapy. The micelles displayed good stability with controlled drug release under physiological environment. Importantly, the iRGD modified polymeric micelles demonstrated favorable ability to cross the BBB and target glioma cells via αv ß integrin and neuropilin-1-mediated ligand transportation in vitro and in vivo. The whole synthesis process is simple and the drug loading content of CPT in the CPT-S-S-PEG-iRGD@IR780 micelles was higher than 10%. Moreover, CPT-S-S-PEG-iRGD@IR780 micelles combined chemotherapy with photodynamic therapy (PDT) displayed more excellent tumor-killing capability than the other groups. Thus, both in vitro and in vivo studies suggested that the targeting prodrug system could not only effectively cross various barriers to reach at glioma site, but also significantly enhance the antitumor effect with laser irradiation. Our findings consequently suggested that CPT-S-S-PEG-iRGD@IR780 micelles with laser irradiation are a promising drug delivery system for glioma therapy.


Assuntos
Glioma , Pró-Fármacos , Barreira Hematoencefálica , Camptotecina , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Humanos , Micelas , Polietilenoglicóis
10.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 26(5): 1010-5, 2009 Oct.
Artigo em Zh | MEDLINE | ID: mdl-19947479

RESUMO

The growth of fibroblasts on the acellular dermal matrix (ADM) was studied. The fibroblasts isolated from the skin of an adult New Zealand Rabbit were cultured in vitro and identified subsequently. After the cells were inoculated on the ADM as seeds, the adhesion rate and the growth ability were examined, and cellular morphology was assayed with DAPI fluorescent staining and Scanning electron microscope (SEM). The possibilities of applying ADM as cells carrier or deliverer in the field of transplantation were evaluated. The result revealed that pure fibroblasts were isolated through the specific method. Skin fibroblasts could adhere to ADM easily, and the adhesion rate was 96.78%, displaying no significant difference (P > 0.05) when compared with that rate of the control holes. The cells on the scaffolds and those on the control holes showed similar growth tendencies, but the activity of the former was lower (P < 0.01). The integral nucleus with blue fluorescence could be observed on the ADM under fluorescence microscope. The number of fibroblasts scaled up with the cultured time, The results of SEM showed that the state of cell was good and the fibroblasts were fused into a layer after being cultured for 5-10d. So rabbit fibroblasts can attach, survive, grow and proliferate on the ADM in a healthy way. It is entirely possible to use ADM as an appropriate scaffold material for the culture of fibroblasts and as a material for transplantations.


Assuntos
Derme/citologia , Fibroblastos/citologia , Pele Artificial , Pele/citologia , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis , Adesão Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Coelhos , Alicerces Teciduais
11.
Int J Pharm ; 474(1-2): 112-22, 2014 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-25138252

RESUMO

Combination of more than one therapeutic strategy is the standard treatment in clinics. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a nanoparticulate system will suppress the tumor growth. In the present study, docetaxel (DTX) and BCL-2 siRNA was incorporated in a PEGylated liposome to systemically deliver in a lung cancer model (A549). The resulting nanoparticle (lipo-DTX/siRNA) was stable and exhibited a sustained release profile. The co-delivery of therapeutic moieties inhibited the cell proliferation (A549 and H226) in a time-dependent manner. Moreover, the co-delivery system of DTX and siRNA exhibited a remarkable apoptosis of cancer cells with elevated levels of caspase 3/7 activity (apoptosis markers). Cell cycle analysis further showed remarkable increase in sub-G0/G1 phase, indicating increasing hypodiploids or apoptotic cells. Pharmacokinetic study showed a long circulating profile for DTX from lipo-DTX/siRNA system facilitating the passive tumor targeting. In vivo antitumor study on A549 cell bearing xenograft tumor model exhibited a remarkable tumor regression profile for lipo-DTX/siRNA with 100% survival rate. The favorable tumor inhibition response was attributed to the synergistic effect of DTX potency and MDR reversing ability of BCL-2 siRNA in the tumor mass. Overall, experimental results suggest that co-delivery of DTX and siRNA could be promising approach in the treatment of lung cancers.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/uso terapêutico , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Docetaxel , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Humanos , Lipossomos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , RNA Interferente Pequeno/farmacocinética , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Taxoides/farmacocinética , Taxoides/farmacologia
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