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1.
Carbohydr Polym ; 227: 115349, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590840

RESUMO

Release of Zn2+ ions from zinc oxide nanoparticles (ZnO NPs) is a major mechanism for oligodynamic activities of these metal oxide NPs against eukaryotic and prokaryotic microorganisms. In addition to this mechanism, ZnO NPs can form reactive oxygen species (ROSs) resulted from electron-hole formation under certain light wavelength. These properties with suitable biocompatibility and biodegradability of ZnO NPs compared to other metal NPs have caused higher applications of these nanomaterials in therapeutic and cosmetic fields. Recently, natural polymers including cellulose, chitosan, and alginate polymers have gained more attention as safe and cost-effective scaffold for wound healing. Both ZnO NPs and these polymers have not been able to satisfy related patients. In this way, the coupling of these materials and nanomaterials as nanocomposites (NCs) is an alternative way to increase the mechanical and antibacterial properties of wound-healing tissue scaffolds. Controllable release of Zn2+ ions in physiological medium should be considered as an indispensable factor to obtain appropriate industrial formulation. Therefore, in this review, attempts were made to highlight particularly important antibacterial results of these NCs in recent investigations.


Assuntos
Alginatos , Antibacterianos , Celulose , Quitosana , Hidrogéis , Nanocompostos , Nanopartículas , Óxido de Zinco , Alginatos/administração & dosagem , Alginatos/química , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Celulose/administração & dosagem , Celulose/química , Quitosana/administração & dosagem , Quitosana/química , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/química , Nanocompostos/administração & dosagem , Nanocompostos/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Cicatrização , Óxido de Zinco/administração & dosagem , Óxido de Zinco/química
2.
Carbohydr Polym ; 227: 115356, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590850

RESUMO

Chitosan oligosaccharide-valylvaline-stearic acid (CSO-VV-SA) nanomicelles were designed for topical ocular drug delivery, based on peptide transporter-1 (PepT-1) active targeting. Hydrogenated castor oil-40/octoxynol-40 (HCO-40/OC-40) mixed nanomicelles were also prepared according to Cequa, just approved by FDA. Both nanomicelles produced no significant cytotoxicity and difference in human corneal epithelial cells (HCEpiC) and human conjunctival epithelial cells (HConEpiC). The active transport of CSO-VV-SA nanomicelles by PepT-1 was illustrated in the inhibitory test. Ex vivo fluorescence images of frozen sections indicated that the nanomicelles entered the posterior segment mainly through conjunctival route. In vivo precorneal retention study suggested dexamethasone from both nanomicelles could be detected for more than 3 h in rabbit tears. In vivo distribution evaluation of rabbits' eyes showed the delivering efficiency of CSO-VV-SA nanomicelles was not inferior to that of HCO-40/OC-40 mixed nanomicelles. These findings indicated that CSO-VV-SA nanomicelles could become promising candidates for further clinical application.


Assuntos
Anti-Inflamatórios/administração & dosagem , Quitosana/administração & dosagem , Dexametasona/administração & dosagem , Sistemas de Liberação de Medicamentos , Micelas , Nanopartículas/administração & dosagem , Oligossacarídeos/administração & dosagem , Administração Oftálmica , Animais , Anti-Inflamatórios/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Dexametasona/química , Dipeptídeos/administração & dosagem , Dipeptídeos/química , Liberação Controlada de Fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Olho/citologia , Olho/metabolismo , Humanos , Masculino , Nanopartículas/química , Oligossacarídeos/química , Transportador 1 de Peptídeos/metabolismo , Coelhos , Ratos Sprague-Dawley , Ácidos Esteáricos/administração & dosagem , Ácidos Esteáricos/química
3.
Carbohydr Polym ; 227: 115351, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590861

RESUMO

Surfactants have been used as a tool to improve the properties of polymeric nanoparticles (NPs) and to increase the rate of hydrophobic drug release by means of these nanoparticles. In this context, this study evaluated the effect of lecithin on the characteristics of chitosan (CHI) and chondroitin sulfate (CS) nanoparticles, when applied in curcumin (Curc) release. CHI/CS NPs and CHI/CS/Lecithin NPs were prepared by the ionic gelation method, both as standards and containing curcumin. Simultaneous conductimetric and potentiometric titrations were employed to optimize the interaction between the polymers. NPs with hydrodynamic diameter of ∼130 nm and zeta potential of +60 mV were obtained and characterized by HRTEM; their pore size and surface area were also analyzed by BET method, DLS, FTIR, XPS, and fluorescence spectroscopy techniques to assess morphological and surface properties, stability and interaction between polymers and to quantify the loading of drugs. The final characteristics of NPs were directly influenced by lecithin addition, exhibiting enhanced encapsulation efficiency of curcumin (131.8 µg curcumin per mg CHI/CS/Lecithin/Curc NPs). The release of curcumin occurred gradually through a two-stage process: diffusion-controlled dissolution and release of curcumin controlled by dissolution of the polymer. However, the release of curcumin in buffer solution at pH 7.4 was achieved faster in CHI/CS/Lecithin/Curc NPs than in CHI/CS/Curc NPs. in vitro cytotoxic activity evaluation of the curcumin was determined by the MTT assay, observing that free curcumin and curcumin nanoencapsulated in CHI/CS/Curc and CHI/CS/Lecithin/Curc NPs reduced the viability of MCF-7 cells in the 72 h period (by 28.4, 36.0 and 30.7%, P < 0.0001, respectively). These results indicate that CHI/CS/Lecithin NPs have more appropriate characteristics for encapsulation of curcumin.


Assuntos
Quitosana/química , Sulfatos de Condroitina/química , Curcumina/química , Lecitinas/química , Nanopartículas/química , Sobrevivência Celular/efeitos dos fármacos , Quitosana/administração & dosagem , Sulfatos de Condroitina/administração & dosagem , Curcumina/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos , Humanos , Lecitinas/administração & dosagem , Células MCF-7 , Nanopartículas/administração & dosagem
4.
Carbohydr Polym ; 227: 115333, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590864

RESUMO

The gold nanoparticles surface was modified by thioglycolic acid ligand and their surface was coated by the chitosan-grafted-poly(N-vinylcaprolactam) (chitosan-g-PNVCL) copolymer. The cisplatin anticancer drug was loaded into the synthesized nanocarriers and its performance was investigated for the treatment of MCF-7 breast cancer cells in vitro. The synthesized nanoparticles were characterized using FTIR, DLS, TEM, SEM, EDX and TGA analysis. The lower critical solution temperature (LCST) of PNVCL/chitosan and PNVCL/chitosan coated gold nanoparticles were found to be 38 and 39 °C, respectively. The cisplatin loading efficiency, cisplatin release from nanoparticles at different temperatures and pH values as well as the pharmacokinetic studies were examined. The maximum cisplatin release from nanoparticles was achieved at T > LCST (42 °C) and pH of 5. The Korsemeyer-Peppas model was best described the cisplatin release from nanoparticles. The maximum MCF cell death was found to be 92% using cisplatin loaded-gold/TGA/chitosan-g-PNVCL nanoparticles under an induction heating system.


Assuntos
Antineoplásicos , Caprolactama/análogos & derivados , Quitosana , Cisplatino , Ouro , Nanopartículas Metálicas , Polímeros , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Caprolactama/administração & dosagem , Caprolactama/química , Caprolactama/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Quitosana/administração & dosagem , Quitosana/química , Quitosana/farmacocinética , Cisplatino/administração & dosagem , Cisplatino/química , Cisplatino/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Ouro/administração & dosagem , Ouro/química , Humanos , Células MCF-7 , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Polímeros/administração & dosagem , Polímeros/química , Polímeros/farmacocinética
5.
Carbohydr Polym ; 227: 115339, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590870

RESUMO

Poor buffering capacity of chitosan (CS) results in insufficient intracellular gene release which poses the major barrier in gene delivery. Herein, we reconstructed pristine CS with propylamine (PA), (diethylamino) propylamine (DEAPA), and N, N-dimethyl- dipropylenetriamine (DMAMAPA) to obtain a series of alkylamine-chitosan (AA-CS). The introduction of multiple amino groups with rational ratios functionally enhance the buffering capacity of AA-CS, among which DMAPAPA-CS showed buffering capacity of 1.58 times that of chitosan. The reconstructed AA-CS functionally enhance the ability of gene binding and endosomal escape. It was observed that the DMAPAPA-CS/pDNA complexes exhibit a notable gene delivery efficiency, which promotes the functionalization of loaded pDNA. Importantly, the in vivo delivery assay reveals that the deep penetration issue can be resolved using DMAPAPA-CS gene delivery vector. Finally, the DMAPAPA-CS is applied to deliver the therapeutic p53 gene in A549 bearing mice, showing efficient therapeutic potential for cancer.


Assuntos
Aminas/administração & dosagem , Quitosana/administração & dosagem , DNA/administração & dosagem , Endossomos , Técnicas de Transferência de Genes , RNA Interferente Pequeno/administração & dosagem , Proteína Supressora de Tumor p53/genética , Células A549 , Aminas/química , Aminas/farmacocinética , Animais , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Quitosana/farmacocinética , DNA/química , Endocitose , Eritrócitos/efeitos dos fármacos , Feminino , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacocinética
6.
Carbohydr Polym ; 227: 115296, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590872

RESUMO

Cutaneous chronic wounds are characterized by an impaired wound healing which may lead to infection. To surmount this problem, a novel quaternary ammonium chitosan nanoparticles (TMC NPs)/chitosan (CS)composite sponge with asymmetric wettability surfaces was successfully prepared. The optimum concentrations of TMC NPs and CS were 0.2 mg/mL and 2.0%, respectively. The incorporated TMC NPs could improve the antibacterial activity of the CS sponge. Asymmetric modification enables the CS sponge to have hydrophobic outer surface and hydrophilic inner surface. The hydrophobic surface of the sponge shows waterproof and anti-adhesion contaminant properties, whereas the hydrophilic surface preserves water-absorbing capability and efficiently inhibits the growth of bacteria. More importantly, in vivo chronic wound healing model evaluation reveals that TMC NPs/CS composite sponge promotes the wound healing and accelerates re-epithelialization and angiogenesis. And in vivo anti-infection test shows the TMC NPs/CS composite sponge could effectively prevent wound infection. These findings demonstrate that TMC NPs/CS composite sponge is a promising dressing material for chronic wounds.


Assuntos
Antibacterianos/administração & dosagem , Bandagens , Quitosana/administração & dosagem , Nanopartículas/administração & dosagem , Compostos de Amônio Quaternário/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Masculino , Camundongos , Nanopartículas/química , Compostos de Amônio Quaternário/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
7.
Braz J Med Biol Res ; 53(1): e8621, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31859909

RESUMO

The use of specially designed wound dressings could be an important alternative to facilitate the healing process of wounds in the hyperglycemic state. Biocompatible dressings combining chitosan and alginate can speed up wound healing by modulating the inflammatory phase, stimulating fibroblast proliferation, and aiding in remodeling phases. However, this biomaterial has not yet been explored in chronic and acute lesions of diabetic patients. The aim of this study was to evaluate the effect of topical treatment with a chitosan-alginate membrane on acute skin wounds of hyperglycemic mice. Diabetes mellitus was induced by streptozotocin (60 mg · kg-1 · day-1 for 5 days, intraperitoneally) and the cutaneous wound was performed by removing the epidermis using a surgical punch. The results showed that after 10 days of treatment the chitosan and alginate membrane (CAM) group exhibited better organization of collagen fibers. High concentrations of interleukin (IL)-1α, IL-1ß, granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α) were detected in the first and second days of treatment. G-CSF and TNF-α level decreased after 5 days, as well as the concentrations of TNF-α and IL-10 compared with the control group (CG). In this study, the inflammatory phase of cutaneous lesions of hyperglycemic mice was modulated by the use of CAM, mostly regarding the cytokines IL-1α, IL-1ß, TNF-α, G-CSF, and IL-10, resulting in better collagen III deposition. However, further studies are needed to better understand the healing stages associated with CAM use.


Assuntos
Alginatos/administração & dosagem , Bandagens , Proliferação de Células/efeitos dos fármacos , Quitosana/administração & dosagem , Diabetes Mellitus Experimental/fisiopatologia , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/administração & dosagem , Biomarcadores/sangue , Colágeno/efeitos dos fármacos , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo
8.
Int J Nanomedicine ; 14: 8179-8193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632026

RESUMO

Background: Chlamydia psittaci is a zoonotic bacteria closely associated with psittacosis/ornithosis. Vaccination has been recognized as the best way to inhibit the spread of C. psittaci due to the majority ignored of infections. The optimal Chlamydia vaccine was obstructed by the defect of single immunization route and the lack of availability of nontoxic and valid adjuvants. Methods: In this study, we developed a novel immunization strategy, simultaneous (SIM) intramuscular (IM) and intranasal (IN) administration of a C. psittaci antigens (Ags) adjuvanted with chitosan nanoparticles (CNPs). And SIM-CNPs-Ags were used to determine the different types of immune response and the protective role in vivo. Results: CNPs-Ags with zeta-potential values of 13.12 mV and of 276.1 nm showed excellent stability and optimal size for crossing the mucosal barrier with high 71.7% encapsulation efficiency. SIM-CPN-Ags mediated stronger humoral and mucosal responses by producing meaningfully high levels of IgG and secretory IgA (sIgA) antibodies. The SIM route also led to Ags-specific T-cell responses and increased IFN-γ, IL-2, TNF-α and IL-17A in the splenocyte supernatants. Following respiratory infection with C. psittaci, we found that SIM immunization remarkably reduced bacterial load and the degree of inflammation in the infected lungs and made for a lower level of IFN-γ, TNF-α and IL-6. Furthermore, SIM vaccination with CNPs-Ags had obviously inhibited C. psittaci disseminating to various organs in vivo. Conclusion: SIM immunization with CNPs-adjuvanted C. psittaci Ags may present a novel strategy for the development of a vaccine against the C. psittaci infection.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Quitosana/administração & dosagem , Chlamydophila psittaci/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Nanopartículas/administração & dosagem , Administração Intranasal , Animais , Antígenos de Bactérias/imunologia , Citocinas/metabolismo , Feminino , Imunidade Humoral , Imunidade nas Mucosas , Imunoglobulina G/metabolismo , Injeções Intramusculares , Pulmão/patologia , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Tamanho da Partícula , Psitacose , Baço/imunologia , Baço/microbiologia , Linfócitos T/imunologia , Vacinação
9.
Biomed Mater Eng ; 30(4): 349-364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31476140

RESUMO

BACKGROUND: Platelet-rich plasma (PRP) has been used to solubilize freeze-dried chitosan (CS) formulations to form injectable implants for tissue repair. OBJECTIVE: To determine whether the in vitro performance of the formulations depends on the type of PRP preparation used to solubilize CS. METHODS: Formulations containing 1% (w/v) CS with varying degrees of deacetylation (DDA 80.5-84.8%) and number average molar mass (Mn 32-55 kDa), 1% (w/v) trehalose and 42.2 mM calcium chloride were freeze-dried. Seven different PRP preparations were used to solubilize the formulations. Controls were recalcified PRP. RESULTS: CS solubilization was achieved with all PRP preparations. CS-PRP formulations were less runny than their corresponding PRP controls. All CS-PRP formulations had a clotting time below 9 minutes, assessed by thromboelastography, while the leukocyte-rich PRP controls took longer to coagulate (>32 min), and the leukocyte-reduced PRP controls did not coagulate in this dynamic assay. In glass culture tubes, all PRP controls clotted, expressed serum and retracted (43-82% clot mass lost) significantly more than CS-PRP clots (no mass lost). CS dispersion was homogenous within CS-PRP clots. CONCLUSIONS: In vitro performance of the CS-PRP formulations was comparable for all types of PRPs assessed.


Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Plasma Rico em Plaquetas/química , Materiais Biocompatíveis/administração & dosagem , Coagulação Sanguínea , Quitosana/administração & dosagem , Liofilização , Humanos , Injeções , Masculino , Próteses e Implantes , Solubilidade , Cicatrização
10.
AAPS PharmSciTech ; 20(7): 299, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31482286

RESUMO

The integrity of the nasal epithelium plays a crucial role in the airway defence mechanism. The nasal epithelium may be injured as a result of a large number of factors leading to nose bleeds, also known as epistaxis. However, local measures commonly used to treat epistaxis and improve wound healing present several side effects and patient discomfort. Hence, this study aims to address some of these drawbacks by developing a new formulation for nasal epithelial wound healing. Chitosan, a biodegradable and biocompatible polymer, was used to develop a thermosensitive nasal formulation for the delivery of tranexamic acid (TXA), one of the most effective pharmacological options to control bleeding with cost and tolerability advantages. The in situ gelation properties of the formulation upon administration in the nasal cavity were investigated in terms of gelation time and temperature. It was found that the developed formulation can undergo rapid liquid-to-gel phase change within approximately 5 min at 32°C, which is well within the human nasal cavity temperature range. The spray pattern, deposition and droplet size generated by the nasal spray was also characterised and were found to be suitable for nasal drug delivery. It was also observed that the in situ gelation of the formulation prevent nasal runoff, while the majority of drug deposited mainly in the anterior part of the nose with no lung deposition. The developed formulation was shown to be safe on human nasal epithelium and demonstrated six times faster wound closure compared to the control TXA solution.


Assuntos
Quitosana/administração & dosagem , Modelos Biológicos , Sprays Nasais , Ácido Tranexâmico/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Intranasal , Quitosana/química , Quitosana/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Géis , Humanos , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Temperatura Ambiente , Ácido Tranexâmico/química , Ácido Tranexâmico/metabolismo , Cicatrização/fisiologia
11.
In Vivo ; 33(5): 1455-1461, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31471392

RESUMO

BACKGROUND/AIM: Idiopathic pulmonary fibrosis (PF) is a fatal disorder of unknown aetiology with limited treatment options. Chitosan has antibacterial, antifungal, antioxidant, antitumour, and anti-inflammatory effects. This study aimed to investigate the effects of chitosan administration on bleomycin (BLM)-induced PF in rats. MATERIALS AND METHODS: A PF rat model was established by endotracheal instillation of 5 mg/kg BLM; then, chitosan was administered in drinking water for 3 weeks. Histology, cell counts, and cytokine responses in the bronchoalveolar lavage fluid (BALF) and weight measurements (body and lung) were analyzed to assess its therapeutic effects. RESULTS: Chitosan administration tended to reduce transforming growth factor (TGF)-ß1 and interferon (IFN)-γ levels in BALF, and histopathological examination confirmed that chitosan attenuated the degree of inflammation and fibrosis in the lung. CONCLUSION: This study revealed that oral chitosan exhibits potential antifibrotic effects, as measured by decreased proinflammatory cytokine levels and histological evaluation, in a BLM-induced PF rat model.


Assuntos
Bleomicina/efeitos adversos , Quitosana/administração & dosagem , Substâncias Protetoras/administração & dosagem , Fibrose Pulmonar/etiologia , Administração Oral , Animais , Biópsia , Modelos Animais de Doenças , Progressão da Doença , Imuno-Histoquímica , Masculino , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Ratos , Resultado do Tratamento
12.
Int J Pharm ; 569: 118592, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31386881

RESUMO

Nasal vaccination is considered to be an effective and convenient way of increasing immune responses both systemically and locally. Although various nanovaccine carriers have been introduced as potential immune adjuvants, further improvements are still needed before they can be taken to clinical usage. Chitosan-based nanovaccine carriers are one of the most widely studiedadjuvants, owing to the abilityof chitosan toopen tight junctions between nasal epithelial cells and enhance particle uptake as well as its inherent immune activating role. In present study, bovine serum albumin (BSA) loaded nanoparticles were prepared using novel aminated (aChi) and aminated plus thiolated chitosan (atChi) polymers, to further enhance mucoadhesiveness and adjuvanticity of the vaccine system by improving electrostatic interactions of polymers with negatively charged glycoproteins. Nanocarriers with optimum size and surface charge, high encapsulation efficiency of model antigen and good stability were developed. Negligible toxicity was observed in Calu-3 and A549 cell lines. In vivo studies, revealed high levels of systemic antibodies (IgG, IgG1 and IgG2a) throughout the study and presence of sIgA in vaginal washes showed that common mucosal system was successfully stimulated. Cytokine levels indicated a mixed Th1/Th2 immune response. A shift towards cellular immune responses was observed after nasal immunisation with antigen loaded nanoparticle formulations. These nanoparticles exhibit great potential for nasal application of vaccines.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antígenos/administração & dosagem , Quitosana/administração & dosagem , Nanopartículas/administração & dosagem , Mucosa Nasal , Soroalbumina Bovina/administração & dosagem , Vacinas/administração & dosagem , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Camundongos Endogâmicos BALB C , Baço/imunologia , Vacinação
13.
Nat Commun ; 10(1): 3523, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388014

RESUMO

Injectable hydrogels can fill irregular defects and promote in situ tissue regrowth and regeneration. The ability of directing stem cell differentiation in a three-dimensional microenvironment for bone regeneration remains a challenge. In this study, we successfully nanoengineer an interconnected microporous networked photocrosslinkable chitosan in situ-forming hydrogel by introducing two-dimensional nanoclay particles with intercalation chemistry. The presence of the nanosilicates increases the Young's modulus and stalls the degradation rate of the resulting hydrogels. We demonstrate that the reinforced hydrogels promote the proliferation as well as the attachment and induced the differentiation of encapsulated mesenchymal stem cells in vitro. Furthermore, we explore the effects of nanoengineered hydrogels in vivo with the critical-sized mouse calvarial defect model. Our results confirm that chitosan-montmorillonite hydrogels are able to recruit native cells and promote calvarial healing without delivery of additional therapeutic agents or stem cells, indicating their tissue engineering potential.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Hidrogéis/administração & dosagem , Nanocompostos/administração & dosagem , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos , Animais , Bentonita/administração & dosagem , Bentonita/química , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Diferenciação Celular/efeitos dos fármacos , Quitosana/administração & dosagem , Quitosana/química , Modelos Animais de Doenças , Módulo de Elasticidade , Humanos , Hidrogéis/química , Masculino , Células-Tronco Mesenquimais , Camundongos , Nanocompostos/química , Osteogênese/efeitos dos fármacos , Crânio/diagnóstico por imagem , Crânio/efeitos dos fármacos , Crânio/lesões , Microtomografia por Raio-X
14.
Biomater Sci ; 7(10): 4375-4387, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31429425

RESUMO

Sulfated polysaccharides have received much attention in recent years due to their special biological activities, especially the regulation of the biological activity of growth factors such as the representative inductive growth factor recombinant human bone morphogenetic protein-2 (rhBMP-2). However, the regulatory mechanisms from the aspect of the molecular chain structure have rarely been reported. In this article, we selected three kinds of sulfonates containing different backbone structures and functional groups, 2-N,6-O-sulfated chitosan (26 SCS), sulfated dextran (DSS) and poly(sodium-p-styrenesulfonate) (PSS), to explore the interaction between them and rhBMP-2. From in vivo and in vitro osteogenesis-related experiments, 26 SCS showed the best promoting effect on rhBMP-2 induced osteogenic differentiation and the sulfated amino group in 26 SCS could specifically bind to rhBMP-2. These findings indicated that the polysaccharide chain structure was a prerequisite for the synergy effect between 26 SCS and rhBMP-2; the effective combination of -SO3- and rhBMP-2 was an important factor in protecting the bioactivity of rhBMP-2. In addition, the presence of the sulfated amino group was the key factor in the specific binding between 26 SCS and rhBMP-2 and provided the possibility of capturing factors in vivo.


Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Quitosana/administração & dosagem , Sulfato de Dextrana/administração & dosagem , Osteogênese/efeitos dos fármacos , Polímeros/administração & dosagem , Ácidos Sulfônicos/administração & dosagem , Fator de Crescimento Transformador beta/administração & dosagem , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Regeneração Óssea/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Masculino , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/administração & dosagem
15.
Int J Pharm ; 567: 118489, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31276760

RESUMO

This study systematically demonstrated the antigenicity kinetics of HBV vaccine microneedles (MNs) during the fabrication, application and storage. To improve the stability of HBsAg in a microneedle patch, several selected saccharides were added to the MN formulations as stabilizers. According to the experimental data, no significant decrease of the bio-activity of HBsAg antigen was found during the microneedle fabrication process. And then immune effects of HBsAg added with different sugars were tested. Chitosan and trehalose loaded HBsAg MNs enhanced the antibody levels to approximately 1.5-fold and 2-fold of the plain HBsAg MNs respectively while sucrose and glucose were not obviously beneficial. During the short-term storage under 60 °C, the antigenicity of HBsAg MNs encapsulated with glucose and chitosan declined sharply in 24 h and hardly left after 7 days. As for the groups of HBsAg MNs added with sucrose and trehalose, approximately 90% of HBsAg initial antigenicity maintained, which could be attributed to the protective function of non-reductive disaccharides. As for the long-term storage experiments, the pharmacological activity of HBsAg antigen protected by sucrose and trehalose slightly reduced in 3 months except for the samples under 60 °C. In extreme condition, trehalose performed even better protection function than sucrose, of which the antigenicity of HBsAg in MNs left approximately 81% and 63% of its initial, respectively. These results confirmed that trehalose loaded HBsAg MNs enabled stable encapsulation and storage of HBsAg antigen and realized reasonable enhancement of immune effect in a relatively painless, safe, and convenient manner.


Assuntos
Antígenos de Superfície da Hepatite B/administração & dosagem , Vacinas contra Hepatite B/administração & dosagem , Trealose/administração & dosagem , Animais , Quitosana/administração & dosagem , Estabilidade de Medicamentos , Feminino , Anticorpos Anti-Hepatite B/sangue , Cinética , Camundongos Endogâmicos BALB C , Microinjeções , Agulhas , Sacarose/administração & dosagem , Adesivo Transdérmico
16.
Mar Drugs ; 17(7)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269758

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Chitosan oligosaccharide (COS) is widely known to have various biological effects, and in this study we aimed to evaluate the liver-protective effect in diet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly composed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome were performed to assess the effects of COS23 on lipids in plasma and the liver as well as on intestinal microbiota. Our results revealed that COS23 obviously attenuated hepatic steatosis and ameliorated liver injury in diet-induced obese mice. The hepatic toxic lipids-especially triglycerides (TGs) and free fatty acids (FFAs)-were decreased dramatically after COS23 treatment. COS23 regulated lipid-related pathways, especially inhibiting the expressions of FFA-synthesis-related genes and inflammation-related genes. Furthermore, COS23 could alter lipid profiles in plasma. More importantly, COS23 also decreased the abundance of Mucispirillum and increased the abundance of Coprococcus in gut microbiota and protected the intestinal barrier by up-regulating the expression of tight-junction-related genes. In conclusion, COS23, an enzymatically digested product of COS, might serve as a promising candidate in the clinical treatment of NAFLD.


Assuntos
Quitosana/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/complicações , Oligossacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Administração Oral , Animais , Quitosana/química , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos não Esterificados/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/etiologia , Oligossacarídeos/química , Substâncias Protetoras/química , Triglicerídeos/metabolismo
17.
Int J Pharm ; 568: 118506, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31302169

RESUMO

This study compared the in vitro and in vivo effects of different aliphatic acid grafted N-trimethyl chitosan (TMC) surface-modified nanostructured lipid carriers (NLC) by oral delivery. Medium-chain fatty acids, decylic acids (DA), and long-chain fatty acids, palmitic acids (PA) were selected as contrasting objects. TMC, DA grafted TMC (DA-TMC), and PA grafted TMC (PA-TMC) were successively synthesized. Kaempferol loaded NLC (KNLC), KNLC coated with DA-TMC (DA-TMC-KNLC) and PA-TMC (PA-TMC-KNLC) were fabricated, respectively. KNLC were subspherical in shape at nano-size limits. The particle size increased from 93.6 to 125.5 nm and the zeta potential changed from negative to positive due to surface-modification. The KNLC surface-modified with different aliphatic acid grafted TMC displayed a diverse release profiles at the simulative physiological environment, which contrasted that of KNLC. Pharmacokinetic studies demonstrated that the nanoparticles all could improve the AUC values and prolong blood retention times compared to that of kaempferol suspensions. Cell uptake and in situ intestinal perfusion experiments revealed that DA-TMC-KNLC and PA-TMC-KNLC could remarkably enhance cellular uptake of kaempferol into Caco-2 cells and drug absorption in each intestinal segment in comparison with KNLC, repectively. Wherein, DA-TMC-KNLC exhibits the greatest uptake and absorption efficiency as compared to kaempferol suspensions, KNLC and PA-TMC-KNLC. Collectively, DA-TMC surface-modified NLC might serve as a potential drug carrier for oral delivery of water-insoluble flavonoid ingredients.


Assuntos
Quitosana/administração & dosagem , Portadores de Fármacos/administração & dosagem , Ácidos Graxos/administração & dosagem , Quempferóis/administração & dosagem , Nanoestruturas/administração & dosagem , Administração Oral , Animais , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Quitosana/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Ácidos Graxos/química , Ácidos Graxos/farmacocinética , Humanos , Quempferóis/química , Quempferóis/farmacocinética , Masculino , Nanoestruturas/química , Tamanho da Partícula , Ratos Sprague-Dawley
18.
Eur J Pharm Sci ; 137: 105002, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302215

RESUMO

Here, we introduce core-shell nanofibers based on chitosan (CS)-loaded poly (ε-caprolactone) (PCL) shell and 5-fluorouracil (5-FU)-loaded Poly(N-vinyl-2-pyrrolidone) (PVP) core for synergistic therapy of melanoma skin cancer. The yielded nanofibers exhibited an average diameter of 503 nm with high drug-encapsulating efficiency and good mechanical properties. Moreover, the burst release of 5-FU significantly inhibited melanoma skin cancer cells (B16F10 cells), and the sustained release of CS exhibited "remedying effects" on normal skin cells (L929 cells) after suffering adverse effects from 5-FU treatment. For the B16F10 cells, the early apoptosis cells increased from 0.8% to 62.2% after being treated with blended films loaded with 5-FU (2 wt%) for 24 h; for the L929 cells, the vital cells increased from 68.9% to 77.0%, and the early apoptosis of stage cells decreased from 12.3% to 10.9% after being treated with blended films with CS (8 wt%) for 24 h. In conclusion, the results introduced in this work can be a promising strategy for cancer treatment and possesses synergism potential to broaden an avenue for chemotherapeutic therapy with minimum adverse effects on normal cells.


Assuntos
Antineoplásicos/administração & dosagem , Quitosana/administração & dosagem , Sistemas de Liberação de Medicamentos , Fluoruracila/administração & dosagem , Nanofibras/administração & dosagem , Poliésteres/administração & dosagem , Povidona/administração & dosagem , Animais , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quitosana/química , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Fluoruracila/química , Melanoma Experimental/tratamento farmacológico , Camundongos , Nanofibras/química , Poliésteres/química , Povidona/química , Neoplasias Cutâneas/tratamento farmacológico
19.
Int J Pharm ; 569: 118578, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31362096

RESUMO

Chitosan (CS), due to its inherent mucoadhesive property and biofilm penetration ability, can be considered as very potent vehicle for local drug delivery to the lungs. This study reports on the preparation and in vitro antibacterial activity and cytotoxicity determination of ciprofloxacin loaded chitosan (Cipro-CS) microparticles with size in the range of 0.1-1 µm, which may provide advantages of lower nanotoxicity and lower local clearance. Cipro-CS microparticles were prepared by ionic gelation method and their size, zeta potential and drug release pattern determined. The antibacterial activities of CS and Cipro-CS microparticles against pneumonia causing agents, namely Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, were evaluated by determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The biocompatibility of the microparticles was tested in the human lung epithelial cell (BEAS-2B) culture, and microparticle association with the bacteria and epithelial cells was evaluated by transmission electron microscopy. Only the Cipro-CS microparticles, but not the CS microparticles, inhibited bacterial growth at concentrations not significantly cytotoxic to BEAS-2B cells. The Cipro-CS microparticles were able to damage the cell wall and membrane of the bacteria, and the ones ≤200 nm in size were internalized by both the BEAS-2B cells and the microorganisms.


Assuntos
Antibacterianos/administração & dosagem , Quitosana/administração & dosagem , Ciprofloxacino/administração & dosagem , Células Epiteliais/efeitos dos fármacos , Nanopartículas/administração & dosagem , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Ciprofloxacino/química , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Pulmão/citologia , Testes de Sensibilidade Microbiana , Nanopartículas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
20.
Int J Pharm ; 569: 118562, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31351178

RESUMO

The purpose of this study was to explore the influence of stabilizer type and concentration on the properties of spray dried nanosuspension-in-microparticles (NS-in-MPs) for inhalation. Taking resveratrol (RES) as a Biopharmaceutical Classification System II (BCS II) model drug, the RES containing nanosuspensions were fabricated by high pressure homogenization method with different stabilizers including sodium dodecyl sulphate (SDS), sodium alginate (SA), chitosan (CS) and polyvinyl alcohol (PVA). Then, the nanosuspensions were spray dried with mannitol to obtain inhalable NS-in-MPs. The particle size, morphology, drug existing state, in vitro aerodynamic performance, in vitro release behavior, lung retention and pharmacokinetic behaviors were characterized. It was found that the morphology, lung deposition as well as in vitro drug release from the microparticles were significantly influenced by stabilizer type, with 1% PVA as stabilizer presenting the highest fine particle fraction (FPF). Meanwhile, taking PVA as an example, it was found stabilizer concentration could alter morphology and flowability of the microparticles, and the FPF value decreased with the increase of stabilizer concentration. Further drug retention and in vivo pharmacokinetic studies demonstrated that the positively charged stabilizer CS could facilitate drug retention and minimize drug expose to the systemic circulation. In conclusion, the deposition and lung retention behavior of NS-in-MPs could be well tuned by selecting different type or concentration of stabilizers, which could facilitate local lung diseases therapy.


Assuntos
Pulmão/metabolismo , Nanopartículas/administração & dosagem , Resveratrol/administração & dosagem , Alginatos/administração & dosagem , Alginatos/química , Animais , Líquido da Lavagem Broncoalveolar/química , Quitosana/administração & dosagem , Quitosana/química , Dessecação , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Masculino , Nanopartículas/química , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/química , Ratos Sprague-Dawley , Resveratrol/química , Resveratrol/farmacocinética , Dodecilsulfato de Sódio/administração & dosagem , Dodecilsulfato de Sódio/química , Suspensões
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