RESUMO
Hydroxyapatite coated metallic implants favorably combine the required biocompatibility with the mechanical properties. As an alternative to the industrial coating method of plasma spraying with inherently potential deleterious effects, sol-gel methods have attracted much attention. In this study, the effects of intermediate silk fibroin and silk sericin layers on the protein adsorption capacity of hydroxyapatite films formed by a particulate sol-gel method were determined experimentally. The preparation of the layered silk protein/hydroxyapatite structures on glass substrates, and the effects of the underlying silk proteins on the topography of the hydroxyapatite coatings were described. The topography of the hydroxyapatite layer fabricated on the silk sericin was such that the hydroxyapatite particles were oriented forming an oriented crystalline surface. The model protein (bovine serum albumin) adsorption increased to 2.62 µg/cm2 on the latter surface as compared to 1.37 µg/cm2 of hydroxyapatite on glass without an intermediate silk sericin layer. The BSA adsorption on glass (blank), glass/c-HAp, glass/m-HAp, glass/sericin/c-HAp, and glass/sericin/m-HAp substrates, reported as decrease in BSA concentration versus contact time.
Assuntos
Materiais Revestidos Biocompatíveis/farmacocinética , Durapatita/química , Fibroínas/química , Sericinas/química , Soroalbumina Bovina/farmacocinética , Adsorção , Animais , Bovinos , Cerâmica/síntese química , Cerâmica/química , Cerâmica/farmacocinética , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Durapatita/farmacocinética , Fibroínas/farmacocinética , Membranas Artificiais , Microscopia de Força Atômica , Modelos Biológicos , Nanopartículas/química , Sericinas/farmacocinética , Seda/química , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios XRESUMO
Cellular senescence is the progressive impairment of function and proliferation in response to various regulators. Dihydrolipoic acid-coated gold nanoclusters (DHLA-Au NCs), which are molecular clusters with covalently linked dihydroxyl lipoic acid, preserve cellular activities for long-term incubation. DHLA-Au NC delivery was characterized, and we determined the role of growth supplements on internalization, allowing the optimization of DHLA-Au NC bioactivity. In the optimized medium, DHLA-Au NCs attenuated the levels of the senescence-associated phenotype. Molecular mechanism analysis further indicated that during DHLA-Au NC treatment, the activation of the stress signal JNK and its downstream c-Jun were impaired under LPS induction, which led to a decline in AP-1-mediated TNF-α transactivation. Confocal microscopy and subcellular fractionation analysis suggested that DHLA-Au NCs interacted with mitochondria through their lipid moiety and attenuated mitochondria-derived reactive oxygen species. With adequate treatment, DHLA-Au NCs show protection against cellular senescence and inflammation in vitro and in vivo.
Assuntos
Anti-Inflamatórios , Senescência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis , Ouro , MAP Quinase Quinase 4/metabolismo , Nanopartículas Metálicas , Mitocôndrias/metabolismo , Ácido Tióctico/análogos & derivados , Fator de Transcrição AP-1/metabolismo , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Ouro/química , Ouro/farmacologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Ácido Tióctico/química , Ácido Tióctico/farmacocinética , Ácido Tióctico/farmacologiaRESUMO
The use of nanoparticles (NPs) to deliver therapeutics to reproductive organs is an emerging approach to safely and effectively treat mothers and babies facing pregnancy complications. This study investigates the biodistribution of two different sized gold-based NPs in pregnant mice following systemic delivery as a function of gestational age. Poly(ethylene glycol)-coated 15â¯nm gold nanoparticles or 150â¯nm diameter silica core/gold nanoshells were intravenously administered to pregnant mice at gestational days (E)9.5 or 14.5. NP distribution was analyzed twenty-four hours later by inductively coupled plasma-mass spectrometry and silver staining of histological specimens. More NPs accumulated in placentas than embryos and delivery to these tissues was greater at E9.5 than E14.5. Neither NP type affected fetal weight or placental weight, indicating minimal short-term toxicity in early to mid-stage pregnancy. These findings warrant continued development of NPs as tools to deliver therapeutics to reproductive tissues safely.
Assuntos
Materiais Revestidos Biocompatíveis , Embrião de Mamíferos/metabolismo , Idade Gestacional , Ouro , Nanopartículas Metálicas , Placenta/metabolismo , Animais , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Feminino , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , GravidezRESUMO
Alzheimer's disease (AD) is the most common neurodegenerative disease, which is associated with extracellular deposition of amyloid-ß proteins (Aß). It has been reported that triptolide (TP), an immunosuppressive and anti-inflammatory agent extracted from a Chinese herb Tripterygium wilfordii, shows potential neuroprotective effects pertinent to AD. However, the clinical use of TP for AD could be hampered due to its high toxicity, instability, poor water solubility, and nonspecific biodistribution after administration. In this paper, we reported a kind of multiple-coated PLGA nanoparticle with the entrapment of TP and surface coated by chitosan hydrochloride, Tween-80, PEG20000, and borneol/mentholum eutectic mixture (MC-PLGA-TP-NP) as a novel nasal brain targeting preparation for the first time. The obtained MC-PLGA-TP-NP was 147.5 ± 20.7 nm with PDI of 0.263 ± 0.075, zeta potential of 14.62 ± 2.47 mV, and the entrapment efficiency and loading efficiency of 93.14% ± 4.75% and 1.17 ± 0.08%, respectively. In comparison of TP, MC-PLGA-TP-NP showed sustained-release profile and better transcellular permeability to Caco-2 cells in vitro. In addition, our data showed that MC-PLGA-TP-NP remarkably reduced the cytotoxicity, attenuated the oxidative stress, and inhibited the increase of the intracellular Ca2+ influx in differentiated PC12 cells induced by Aß 1-42. Therefore, it can be concluded that MC-PLGA-TP-NP is a promising preparation of TP, which exerts a better neuroprotective activity in the AD cellular model.
Assuntos
Doença de Alzheimer , Materiais Revestidos Biocompatíveis , Diterpenos , Portadores de Fármacos , Modelos Neurológicos , Nanopartículas , Fenantrenos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Células CACO-2 , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Diterpenos/química , Diterpenos/farmacocinética , Diterpenos/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Compostos de Epóxi/química , Compostos de Epóxi/farmacocinética , Compostos de Epóxi/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Células PC12 , Fenantrenos/química , Fenantrenos/farmacocinética , Fenantrenos/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , RatosRESUMO
Magnesium (Mg)-based biomaterials hold considerable promise for applications in regenerative medicine. However, the degradation of Mg needs to be reduced to control toxicity caused by its rapid natural corrosion. In the process of developing new Mg alloys with various surface modifications, an efficient assessment of the relevant properties is essential. In the present study, a WE43 Mg alloy with a plasma electrolytic oxidation (PEO)-generated surface was investigated. Surface microstructure, hydrogen gas evolution in immersion tests and cytocompatibility were assessed. In addition, a novel in vitro immunological test using primary human lymphocytes was introduced. On PEO-treated WE43, a larger number of pores and microcracks, as well as increased roughness, were observed compared to untreated WE43. Hydrogen gas evolution after two weeks was reduced by 40.7% through PEO treatment, indicating a significantly reduced corrosion rate. In contrast to untreated WE43, PEO-treated WE43 exhibited excellent cytocompatibility. After incubation for three days, untreated WE43 killed over 90% of lymphocytes while more than 80% of the cells were still vital after incubation with the PEO-treated WE43. PEO-treated WE43 slightly stimulated the activation, proliferation and toxin (perforin and granzyme B) expression of CD8+ T cells. This study demonstrates that the combined assessment of corrosion, cytocompatibility and immunological effects on primary human lymphocytes provide a comprehensive and effective procedure for characterizing Mg variants with tailorable degradation and other features. PEO-treated WE43 is a promising candidate for further development as a degradable biomaterial.
Assuntos
Materiais Revestidos Biocompatíveis , Magnésio/química , Teste de Materiais , Animais , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Corrosão , Equipamentos e Provisões , Humanos , Sistema Imunitário/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/fisiologia , Magnésio/farmacocinética , Magnésio/farmacologia , Compostos de Magnésio/química , Compostos de Magnésio/farmacocinética , Compostos de Magnésio/farmacologia , Teste de Materiais/métodos , Camundongos , OxirreduçãoRESUMO
There is growing interest in developing biomaterial-coated liposome delivery systems to improve the stability and bioavailability of curcumin, which is a hydrophobic nutraceutical claimed to have several health benefits. The curcumin-loaded rhamnolipid liposomes (Cur-RL-Lips) were fabricated from rhamnolipid and phospholipids, and then chitosan (CS) covered the surface of Cur-RL-Lips by electrostatic interaction to form CS-coated Cur-RL-Lips. The influence of CS concentration on the physical stability and digestion of the liposomes was investigated. The CS-coated Cur-RL-Lips with RL:CS = 1:1 have a relatively small size (412.9 nm) and positive charge (19.7 mV). The CS-coated Cur-RL-Lips remained stable from pH 2 to 5 at room temperature and can effectively slow the degradation of curcumin at 80 °C; however, they were highly unstable to salt addition. In addition, compared with Cur-RL-Lips, the bioavailability of curcumin in CS-coated Cur-RL-Lips was relatively high due to its high transformation in gastrointestinal tract. These results may facilitate the design of a more efficacious liposomal delivery system that enhances the stability and bioavailability of curcumin in nutraceutical-loaded functional foods and beverages.
Assuntos
Quitosana , Materiais Revestidos Biocompatíveis , Curcumina , Digestão , Trato Gastrointestinal/metabolismo , Glicolipídeos , Animais , Disponibilidade Biológica , Quitosana/química , Quitosana/farmacocinética , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Curcumina/química , Curcumina/farmacocinética , Glicolipídeos/química , Glicolipídeos/farmacocinética , Humanos , LipossomosRESUMO
Persistent local oxygen delivery is crucial to create a microenvironment for cell survival and nerve regeneration in acute spinal cord injury (SCI). This study aimed to fabricate calcium peroxide-based microspheres incorporated into a 3-D construct scaffold as a novel oxygen release therapy for SCI. The scaffolds were able to generate oxygen over the course of 21 days when incubated under hypoxic conditions. In vitro, GFP-labeled bone marrow-derived mesenchymal stem cells (MSCs) were planted into the scaffolds. We observed that scaffolds could enhance MSC survival under hypoxic conditions for more than 21 days. Oxygen generating scaffolds were transplanted into spinal cord injury sites of rats in vivo. Twelve weeks following transplantation, cavity areas in the injury/graft site were significantly reduced due to tissue regeneration. Additionally, the oxygen generating scaffolds improved revascularization as observed through vWF immunostaining. A striking feature was the occurrence of nerve fiber regeneration in the lesion sites, which eventually led to significant locomotion recovery. The present results indicate that the oxygen generating scaffolds have the property of sustained local oxygen release, thus facilitating regeneration in injured spinal cords.
Assuntos
Materiais Revestidos Biocompatíveis , Regeneração Tecidual Guiada , Oxigênio/farmacocinética , Traumatismos da Medula Espinal/reabilitação , Alicerces Teciduais , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Feminino , Regeneração Tecidual Guiada/instrumentação , Regeneração Tecidual Guiada/métodos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Microesferas , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Oxigênio/metabolismo , Oxigênio/farmacologia , Peróxidos/química , Peróxidos/farmacocinética , Peróxidos/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia , Alicerces Teciduais/químicaRESUMO
Phlorotannins are a group of major polyphenol secondary metabolites found only in brown algae and are known for their bioactivities and multiple health benefits. However, they can be oxidized due to external factors and their bioavailability is low due to their low water solubility. In this study, the potential of utilizing nanoencapsulation with polyvinylpyrrolidone (PVP) to improve various activities of phlorotannins was explored. Phlorotannins encapsulated by PVP nanoparticles (PPNPS) with different loading ratios were prepared for characterization. Then, the PPNPS were evaluated for in vitro controlled release of phlorotannin, toxicity and antioxidant activities at the ratio of phlorotannin to PVP 1:8. The results indicated that the PPNPS showed a slow and sustained kinetic release of phlorotannin in simulated gastrointestinal fluids, they were non-toxic to HaCaT keratinocytes and they could reduce the generation of endogenous reactive oxygen species (ROS). Therefore, PPNPS have the potential to be a useful platform for the utilization of phlorotannin in both pharmaceutical and cosmetics industries.
Assuntos
Antioxidantes , Materiais Revestidos Biocompatíveis , Kelp/classificação , Queratinócitos/metabolismo , Teste de Materiais , Nanopartículas , Povidona/química , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Linhagem Celular , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêuticoRESUMO
To design, develop and study a novel drug delivery system for intraocular applications. The spin coating technique was applied to develop a polymeric, drug-eluting thin film consisting of a blend of organic polymers [poly (D, L lactide coglycolide) lactide: glycolide 75: 25, PLGA and polycaprolactone, PCL] and dexamethasone on the surface of intraocular lenses (IOLs). The initial durability of the IOLs during spinning was assessed. Information about the structural and optical properties of the modified IOLs was extracted using atomic force microscopy, scanning electron microscopy and spectroscopic ellipsometry. A drug release study was conducted for 8 weeks. The IOLs were durable in spinning speeds higher than the ones used to develop thin films. Single-layer thin films were successfully developed on the optics and the haptics of the lenses. The films formed nanopores with encapsulated aggregates of dexamethasone. The spectroscopic ellipsometry showed an acceptable optical transparency of the lenses regardless of the deposition of the drug-eluting films on their surface. The drug release study demonstrated gradual dexamethasone release over the selected period. In conclusion, the novel drug-eluting IOL system exhibited desired properties regarding its transparency and drug release rate. Further research is necessary to assess their suitability as an intraocular drug delivery system.
Assuntos
Materiais Revestidos Biocompatíveis/química , Lentes Intraoculares , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Materiais Revestidos Biocompatíveis/farmacocinética , Dexametasona/química , Dexametasona/farmacocinética , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Microscopia de Força AtômicaRESUMO
A great deal of attention has been focused on nanoparticles for cancer therapy, with the promise of tumor-selective delivery. However, despite intense work in the field over many years, the biggest obstacle to this vision remains extremely low delivery efficiency of nanoparticles into tumors. Due to the cost, time, and impact on the animals for in vivo studies, the nanoparticle field predominantly uses cellular uptake assays as a proxy to predict in vivo outcomes. Extensive research has focused on decreasing macrophage uptake in vitro as a proxy to delay nanoparticle accumulation in the mononuclear phagocytic system (MPS), mainly the liver and spleen, and thereby increase tumor accumulation. We have recently reported novel synthetic methods employing small molecule crosslinkers for the controlled assembly of small nanoparticles into larger aggregates and found that these nanoaggregates had remarkably high surface coverage and low cell uptake, even in macrophages. We further found that this extremely low cellular uptake could be recapitulated on solid gold nanoparticles by densely coating their surface with small molecules. Here we report our studies on the biodistribution and clearance of these materials in comparison to more conventional PEGylated gold nanoparticles. It was expected that the remarkably low macrophage uptake in vitro would translate to extended blood circulation time in vivo, but instead we found no correlation between either surface coverage or in vitro macrophage cell uptake and in vivo blood circulation. Gold nanoaggregates accumulate more rapidly and to a higher level in the liver compared to control gold nanoparticles. The lack of correlation between in vitro macrophage uptake and in vivo blood circulation suggests that the field must find other in vitro assays to use as a primary proxy for in vivo outcomes or use direct in vivo experimentation as a primary assay.
Assuntos
Materiais Revestidos Biocompatíveis/farmacocinética , Ouro/farmacocinética , Nanopartículas Metálicas , Polietilenoglicóis , Animais , Endocitose , Jejum/metabolismo , Feminino , Ouro/administração & dosagem , Ouro/sangue , Meia-Vida , Rim/metabolismo , Fígado/metabolismo , Macrófagos/fisiologia , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/classificação , Camundongos , Especificidade de Órgãos , Projetos Piloto , Células RAW 264.7 , Organismos Livres de Patógenos Específicos , Baço/metabolismo , Distribuição TecidualRESUMO
INTRODUCTION: Bio-degradable nano-particles have many applications as drug delivery vehicles because of their good bio-availability, controlled release, low toxicity and potential for encapsulation. However, the most important obstacle to nanoparticulate drug delivery is elimination by macrophages which reduces the residence time of nanoparticles in the blood. To overcome this problem, the surface of the nanoparticle can be passivated by coating with Polyethylene glycol (PEG). However, the use of PEG has its own disadvantages. CD47 receptor acts as a self marker on the surface of many cells and inhibits phagocytosis. This study used a CD47 mimicry peptide as a substitute for PEG to fabricate "stealth" nanoliposome with reduced macrophage clearance. METHODS: Doxorubibin was used as a model drug because of its inherent fluorescence. Doxorubicin- containing liposomes were coated with different percentages of CD47 mimicry peptide (0.5% and 1%). PEG-functionalized doxorubicin-containing liposomes, were used as a comparator. The liposomal formulations were intravenously injected into mice. Serum was collected at pre-defined time points and tissue samples were taken at 24 hours. Fluorescence was used to determine the concentration doxorubicin in serum, heart, spleen, kidney, liver and lung tissues. RESULTS: Tissue biodistribution and serum kinetic studies indicated that compared with PEG, the use of CD47 mimicry peptide increased the circulation time of doxorubicin in the circulation. Moreover, unwanted accumulation of doxorubicin in the reticuloendothelial tissues (liver and spleen), kidney and heart was significantly decreased by the CD47 mimicry peptide. CONCLUSION: The use of a CD47 mimicry peptide on the surface of nanoliposomes improved the residence time of liposomal doxorubicin in the circulation. The accumulation of drug in non-target tissues was reduced, thereby potentially reducing toxicity.
Assuntos
Antígeno CD47/química , Materiais Revestidos Biocompatíveis , Doxorrubicina , Peptídeos , Animais , Linhagem Celular , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Especificidade de Órgãos , Peptídeos/química , Peptídeos/farmacocinética , Peptídeos/farmacologiaRESUMO
3D multifunctional bone scaffolds have recently attracted more attention in bone tissue engineering because of addressing critical issues like bone cancer and inflammation beside bone regeneration. In this study, a 3D bone scaffold is fabricated from Mg2SiO4-CoFe2O4 nanocomposite which is synthesized via a two-step synthesis strategy and then the scaffold's surface is modified with poly-3-hydroxybutyrate (P3HB)-ordered mesoporous magnesium silicate (OMMS) composite to improve its physicochemical and biological properties. The Mg2SiO4-CoFe2O4 scaffold is fabricated through polymer sponge technique and the scaffold exhibits an interconnected porous structure in the range of 100-600 µm. The scaffold is then coated with OMMS/P3HB composite via dip coating and the physical, chemical, and biological-related properties of OMMS/P3HB composite-coated scaffold are assessed and compared to the non-coated and P3HB-coated scaffolds in vitro. It is found that, on the one hand, P3HB increases the cell attachment, proliferation, and compressive strength of the scaffold, but on the other hand, it weakens the bioactivity kinetic. Addition of OMMS to the coating composition is accompanied with significant increase in bioactivity kinetic. Besides, OMMS/P3HB composite-coated scaffold exhibits higher drug loading capacity and more controlled release manner up to 240 h than the other samples because of OMMS which has a high surface area and ordered mesoporous structure suitable for controlled release applications. The overall results indicate that OMMS/P3HB coating on Mg2SiO4-CoFe2O4 scaffold leads to a great improvement in bioactivity, drug delivery potential, compressive strength, cell viability, and proliferation. Moreover, OMMS/P3HB composite-coated scaffold has heat generation capability for hyperthermia-based bone cancer therapy and so it is suggested as a multifunctional scaffold with great potentials for bone cancer therapy and regeneration.
Assuntos
Neoplasias Ósseas/terapia , Regeneração Óssea , Materiais Revestidos Biocompatíveis , Hipertermia Induzida , Nanocompostos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Cobalto/química , Cobalto/farmacocinética , Cobalto/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Compostos Férricos/química , Compostos Férricos/farmacocinética , Compostos Férricos/farmacologia , Humanos , Hidroxibutiratos , Silicatos de Magnésio/química , Silicatos de Magnésio/farmacocinética , Silicatos de Magnésio/farmacologia , Nanocompostos/química , Nanocompostos/uso terapêutico , Poliésteres , PorosidadeRESUMO
Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy.
Assuntos
Técnicas Eletroquímicas/métodos , Agulhas , Ovalbumina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Administração Cutânea , Animais , Células Cultivadas , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Células Dendríticas , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microinjeções/instrumentação , Nanopartículas/administração & dosagem , Nanopartículas/química , Ovalbumina/administração & dosagem , Ovalbumina/química , Ovalbumina/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinéticaRESUMO
It is known that the size of gold nanoparticles (GNPs) is not the only determining factor in the uptake by cells such as cancer cells. The surface functionalization plays a crucial role, in particular the nature of the ligand as well as the molecular weight and the grafting density. Here, poly(2-hydroxy ethyl) acrylate (pHEA) with molecular weights ranging from 10, 20 to 39 g mol-1 via reversible addition-fragmentation chain transfer polymerization is synthesized. These polymers are used directly to coat GNPs with sizes of 20, 40, and 70 nm as the trithiocarbonate functionality can strongly bind to the gold surface. The library of nine GNP is found to be nontoxic against lung carcinoma cells A549 and has negligible albumin protein absorption as determined by quartz crystal microbalance. Laser scanning confocal microscopy and flow cytometry reveal that GNP coated with medium length pHEA displays the highest cellular uptake while the effect of the size is not statistically significant. In contrast, multicellular tumor spheroids, which is a 3D model that simulates the tissue, enable the penetration of GNP coated with the longest pHEA chain while it also appears that smaller GNPs have now a clear advantage.
Assuntos
Acrilatos , Materiais Revestidos Biocompatíveis , Ouro , Neoplasias Pulmonares/metabolismo , Nanopartículas Metálicas/química , Polímeros , Esferoides Celulares/metabolismo , Células A549 , Acrilatos/química , Acrilatos/farmacocinética , Acrilatos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Polímeros/química , Polímeros/farmacocinética , Polímeros/farmacologia , Técnicas de Microbalança de Cristal de Quartzo , Esferoides Celulares/patologiaRESUMO
The poly (ε-caprolactonediol) based polyurethane (PCL-Diol-b-PU)/poly(N-isopropylacrylamide)-grafted-chitosan (PNIPAAm-g-chitosan) core-shell nanofibers were synthesized via coaxial electrospinning process. Paclitaxel and 5-FU anticancer drugs were incorporated into the core of nanofibers. The nanofibers surface was coated using magnetic gold nanoparticles and the potential of synthesized nanofibers was investigated for the sustained release of paclitaxel and 5-FU toward 4T1 breast cancer cells death in vitro and in vivo. The synthesized magnetic nanoparticles were characterized using SEM, TEM, XRD and DLS analysis. The surface morphology of nanofibers was studied under various applied voltage and different shell flow rates. The paclitaxel and 5-FU release profiles from nanofibers were examined under acidic and physiological pH. The maximum 4T1 cell killing was found to be 78% using magnetic gold coated-nanofibers in the presence of external magnetic field. The SEM images after incubation of nanofibers in 4T1 breast cancer cells indicated the well adhesion of cells on the nanofibers surface. The in vivo studies showed that the tumor volume did not change during 10â¯days. The minimum increase in tumor volume was obtained using paclitaxel and 5-FU loaded-nanofibers coated by the magnetic gold nanoparticles. The obtained results demonstrated the high therapeutic efficiency of synthesized nanofibrous carrier toward breast cancer treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Portadores de Fármacos , Neoplasias Mamárias Animais/tratamento farmacológico , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Resinas Acrílicas/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Fluoruracila/química , Fluoruracila/farmacocinética , Fluoruracila/farmacologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Nanopartículas Magnéticas de Óxido de Ferro/química , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanofibras/química , Nanofibras/uso terapêutico , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Poliésteres/química , Poliésteres/farmacocinética , Poliuretanos/química , Poliuretanos/farmacocinética , Poliuretanos/farmacologiaRESUMO
Drug delivery to the posterior eye is limited by epithelial and mucosal barriers limiting the topical administration of drugs leading to invasive modes of repeated long-term painful administration of drugs. Several constructs of liposomes have been prepared to counter this challenge yet are often limited by size and surface charge resulting in poor encapsulation efficiency, low retention time, and poor permeability. In the present study, chitosan coated liposomes (CCL) were prepared to address these challenges. Conventional liposomes encapsulating Triamcinolone Acetonide (TA) were compared with their chitosan coated counterpart for drug loading and release studies. CCL showed a higher encapsulation efficiency (74%), and a highly positive surface charge (+41.1Mv), increased retention time and sustained release. Choroidal neovascularization (CNV) rat models were generated to assess the efficiency of CCLs as nanocarriers in drug delivery. Significant amount of TA was found to be present and retaining in the eye after fifteen days of treatment with CCL, as shown by HPLC analysis. The results showed successful penetration of the construct via corneal mucosal barrier and its accumulation in vitreous body. The analysis shows that this chitosan based liposomal construct can be employed as a potential topical delivery system for treating posterior segment diseases.
Assuntos
Quitosana , Neovascularização de Coroide/tratamento farmacológico , Materiais Revestidos Biocompatíveis , Triancinolona , Animais , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Preparações de Ação Retardada , Modelos Animais de Doenças , Humanos , Lipossomos , Ratos , Triancinolona/química , Triancinolona/farmacocinética , Triancinolona/farmacologiaRESUMO
In this study, the authors developed pectin-stabilised selenium nanoparticles (pectin-SeNPs) for curcumin (Cur) encapsulation and evaluated their physicochemical properties and biological activities. Results showed that pectin-SeNPs and Cur-loaded pectin-SeNPs (pectin-SeNPs@Cur) exhibited monodisperse and homogeneous spherical structures in aqueous solutions with mean particle sizes of â¼61 and â¼119â nm, respectively. Cur was successfully encapsulated into pectin-SeNPs through hydrogen bonding interactions with an encapsulation efficiency of â¼60.6%, a loading content of â¼7.4%, and a pH-dependent and controlled drug release in vitro. After encapsulation was completed, pectin-SeNPs@Cur showed enhanced water solubility (â¼500-fold), dispersibility, and storage stability compared with those of free Cur. Moreover, pectin-SeNPs@Cur possessed significant free radical scavenging ability and antioxidant capacity in vitro, which were stronger than those of pectin-SeNPs. Antitumour activity assay in vitro demonstrated that pectin-SeNPs@Cur could inhibit the growth of HepG2 cells in a concentration-dependent manner, and the nanocarrier pectin-SeNPs exhibited a low cytotoxic activity against HepG2 cells. Therefore, the results suggested that pectin-SeNPs could function as effective nanovectors for the enhancement of the water solubility, stability, and in vitro bioactivities of hydrophobic Cur.
Assuntos
Curcumina/administração & dosagem , Portadores de Fármacos , Nanopartículas/química , Pectinas/química , Selênio/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Curcumina/farmacocinética , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Tamanho da Partícula , SolubilidadeRESUMO
Due to their unique optical properties upconversion nanoparticles (UCNPs) provide exceptionally high contrast for imaging of true nanoparticle distribution in excised human skin. It makes possible to show penetration of solid nanoparticles in skin treated with chemical enhancers. We demonstrated tracing upconversion nanoparticles in excised human skin by means of optical microscopy at the discrete particle level sensitivity to obtain their penetration profiles, which was validated by laser-ablation inductively-coupled-plasma mass-spectrometry. To demonstrate utilities of our method, UCNPs were coated with polymers, formulated in water and chemical enhancers, and applied on excised human skin mounted on Franz cells, followed by imaging using a custom-built laser-scanning microscope. To evaluate the toxicity impact on skin by polymer-coated UCNPs, we introduced a tissue engineering model of viable epidermis made of decellularized chick embryo skin seeded with keratinocytes. UCNPs formulated in water stopped in stratum corneum, whereas UCNPs formulated in ethanol-water solution crossed stratum corneum and reached viable epidermis - hence, the enhancement effect for solid nanoparticles was detected by optical microscopy. All polymer-coated UCNPs were found nontoxic within the accepted safety levels. The keratinocyte resilience to polyethyleneimine-coated UCNPs was surprising considering cytotoxicity of polyethyleneimine to two-dimensional cell cultures.
Assuntos
Materiais Revestidos Biocompatíveis/química , Nanopartículas/química , Polímeros/química , Pele/metabolismo , Animais , Linhagem Celular , Rastreamento de Células/métodos , Embrião de Galinha , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/farmacocinética , Epiderme/metabolismo , Humanos , Queratinócitos/metabolismo , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Imagem Molecular/métodos , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Oxazinas/química , Polímeros/administração & dosagem , Polímeros/farmacocinética , Pele/citologiaRESUMO
Magnetic nanoparticles coated with protein-specific molecularly imprinted polymers (MIPs) are receiving increasing attention thanks to their binding abilities, robustness, and easy synthesis compared to their natural analogues also able to target proteins, such as antibodies or aptamers. Acting as tailor-made recognition systems, protein-specific MIPs can be used in many in vivo nanomedicine applications, such as targeted drug delivery, biosensing, and tissue engineering. Nonetheless, studies on their biocompatibility and long-term fate in biological environments are almost nonexistent, although these questions have to be addressed before considering clinical applications. To alleviate this lack of knowledge, we propose here to monitor the effect of a protein-specific MIP coating on the toxicity and biodegradation of magnetic iron oxide nanoparticles, both in a minimal aqueous degradation medium and in a model of cartilage tissue formed by differentiated human mesenchymal stem cells. Degradation of iron oxide nanoparticles with or without the polymer coating was monitored for a month by following their magnetic properties using vibrating sample magnetometry and their morphology by transmission electron microscopy. We showed that the MIP coating of magnetic iron oxide nanoparticles does not affect their biocompatibility or internalization inside cells. Remarkably, the imprinted polymer coating does not hinder the magnetic particle degradation but seems to slow it down, although this effect is more visible when degradation occurs in the buffer medium than in cells. Hence, the results presented in this paper are really encouraging and open up the way to future applications of MIP-coated nanoparticles into the clinic.
Assuntos
Materiais Revestidos Biocompatíveis , Sistemas de Liberação de Medicamentos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais , Impressão Molecular , Diferenciação Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Nanopartículas de Magnetita/ultraestrutura , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/ultraestrutura , Células PC-3RESUMO
In solid tumors, increasing drug penetration promotes their regression and improves the therapeutic index of compounds. However, the heterogeneous extracellular matrix (ECM) acts as a steric and interaction barrier that hinders effective transport of therapeutics, including nanomedicines. Specifically, the interactions between the ECM and surface physicochemical properties of nanomedicines (e.g. charge, hydrophobicity) affect their diffusion and penetration. To address the challenges using existing surface chemistries, we used peptide-presenting phage libraries as a high-throughput approach to screen and identify peptides as coatings with desired physicochemical properties that improve diffusive transport through the tumor microenvironment. Through iterative screening against the ECM and identification by next-generation DNA sequencing and analysis, we selected individual clones and quantify their transport by diffusion assays. Here, we identified a net-neutral charge, hydrophilic peptide P4 that facilitates significantly higher diffusive transport of phage than negative control through in vitro tumor ECM. Through alanine mutagenesis, we confirmed that the hydrophilicity, charge, and spatial ordering impact diffusive transport. The P4 phage clone exhibited almost 200-fold improved uptake in ex vivo pancreatic tumor xenografts compared to the negative control. Nanoparticles coated with P4 exhibited â¼40-fold improvement in diffusivity in pancreatic tumor tissues, and P4-coated particles demonstrated less hindered diffusivity through the ECM compared to functionalized control particles. By leveraging the power of molecular diversity using phage display, we can greatly expand the chemical space of surface chemistries that can improve the transport of nanomedicines through the complex tumor microenvironment to ultimately improve their efficacy.