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1.
Int J Nanomedicine ; 15: 4001-4020, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606661

RESUMO

Background: Simvastatin (SMV), a hypocholesterolemic agent, suffers from very low bioavailability due to its poor aqueous solubility and extensive first-pass metabolism. Methods: Two SMV carrier systems, namely, polymeric drug inclusion complex (IC) and mixed micelles (MM) nanoparticles, were developed and loaded into mucoadhesive buccal films to enhance SMV bioavailability. The two carrier systems were characterized and their permeation across human oral epithelial cells (OEC) was studied. The effect of IC to MM ratio (X1) and the mucoadhesive polymer concentration (X2) on the cumulative percent of drug released, elongation percent and the mucoadhesive strength, from the prepared mucoadhesive films, were optimized. Ex vivo permeation across bovine mucosal tissue was investigated. The permeation parameters for the in vitro and ex vivo release data were calculated. Results: Complexation of SMV with hydroxypropyl beta-cyclodextrin (HP ß-CD) was superior to all other polymers as revealed by the equilibrium saturation solubility, stability constant, complexation efficiency and thermodynamic potential. SMV-HP ß-CD IC was utilized to develop a saturated polymeric drug solution. Both carrier systems showed enhanced permeation across OEC when compared to pure drug. X1 and X2 were significantly affecting the characteristics of the prepared films. The optimized mucoadhesive buccal film formulation loaded with SMV IC and drug MM nanoparticles demonstrated superior ex vivo permeation when compared to the corresponding pure drug buccal film, and the calculated permeation parameters confirmed this finding. Conclusion: Mucoadhesive buccal films containing SMV IC and drug MM can be used to improve drug bioavailability; however, additional pharmacokinetic and pharmacodynamic studies are required.


Assuntos
Portadores de Fármacos/química , Liberação Controlada de Fármacos , Mucosa Bucal/efeitos dos fármacos , Muco/química , Sinvastatina/farmacologia , 2-Hidroxipropil-beta-Ciclodextrina/química , Adesividade , Animais , Varredura Diferencial de Calorimetria , Bovinos , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Permeabilidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
2.
Int J Nanomedicine ; 15: 4079-4090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606665

RESUMO

Purpose: The aim of this study is to develop efficient localized therapy of sertaconazole nitrate for the treatment of vaginal candidiasis. Methods: Sertaconazole nitrate-loaded cationic liposomes were prepared by thin-film hydration method and coated with different concentrations of pectin (0.05%, 0.1% and 0.2%) to develop mucoadhesive liposomes. The formulated mucoadhesive vesicles were characterized in terms of morphology, entrapment efficiency, particle size, zeta value, mucoadhesive properties and drug release. The selected formula was incorporated into a gel base and further characterized by an ex vivo permeation study in comparison with conventional sertaconazole gel. Also, the in vivo study was performed to assess the efficacy of sertaconazole mucoadhesive liposomal gel in treating rats with vaginal candidiasis. Results: The mucoadhesive liposomes were spherical. Coating liposomes with pectin results in increased entrapment efficiency and particle size compared with uncoated vesicles. On the contrary, zeta values were reduced upon coating liposomes with pectin indicating efficient coating of liposomes with pectin. Mucoadhesive liposomes showed a more prolonged and sustained drug release compared with uncoated liposomes. Ex vivo study results showed that mucoadhesive liposomal gel increased sertaconazole tissue retention and reduced drug tissue penetration. In the invivo study, the mucoadhesive liposomal gel showed a significant reduction in the microbial count with a subsequent reduction in inflammatory responses with the lowest histopathological change compared with conventional gel. Conclusion: The study confirmed the potentiality of employing mucoadhesive liposomes as a successful carrier for the vaginal delivery of antifungal drugs.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Imidazóis/uso terapêutico , Muco/química , Tiofenos/uso terapêutico , Adesividade , Animais , Anti-Infecciosos/farmacologia , Biomarcadores/metabolismo , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Feminino , Géis , Humanos , Imidazóis/farmacologia , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Mediadores da Inflamação/metabolismo , Lipossomos/ultraestrutura , Mucinas/metabolismo , Tamanho da Partícula , Ratos Sprague-Dawley , Ovinos , Eletricidade Estática , Tiofenos/farmacologia , Vagina/patologia , beta-Glucanas/metabolismo
3.
Proc Natl Acad Sci U S A ; 117(27): 15497-15503, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32576692

RESUMO

Bioadhesives such as tissue adhesives, hemostatic agents, and tissue sealants have potential advantages over sutures and staples for wound closure, hemostasis, and integration of implantable devices onto wet tissues. However, existing bioadhesives display several limitations including slow adhesion formation, weak bonding, low biocompatibility, poor mechanical match with tissues, and/or lack of triggerable benign detachment. Here, we report a bioadhesive that can form instant tough adhesion on various wet dynamic tissues and can be benignly detached from the adhered tissues on demand with a biocompatible triggering solution. The adhesion of the bioadhesive relies on the removal of interfacial water from the tissue surface, followed by physical and covalent cross-linking with the tissue surface. The triggerable detachment of the bioadhesive results from the cleavage of bioadhesive's cross-links with the tissue surface by the triggering solution. After it is adhered to wet tissues, the bioadhesive becomes a tough hydrogel with mechanical compliance and stretchability comparable with those of soft tissues. We validate in vivo biocompatibility of the bioadhesive and the triggering solution in a rat model and demonstrate potential applications of the bioadhesive with triggerable benign detachment in ex vivo porcine models.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Ferida Cirúrgica/terapia , Adesivos Teciduais/química , Adesividade , Animais , Reagentes para Ligações Cruzadas/química , Modelos Animais de Doenças , Feminino , Teste de Materiais , Ratos , Bicarbonato de Sódio/química , Soluções , Succinimidas/química , Suínos , Técnicas de Fechamento de Ferimentos/instrumentação
4.
AAPS PharmSciTech ; 21(5): 142, 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32419061

RESUMO

Mucoadhesion-based drug delivery systems have recently gained interest because of their bio-adhesion capability, which results in enhanced residence time leading to prolonged duration of action with the mucosal surface, potentially improving compliance and convenience. Mucoadhesion testing of these formulations is widely reported; however, this is technically challenging due to the absence of any standard methods and difficulty in conducting mucoadhesion, formulation-mucosal surface interaction, mucosal surface topography and drug release in a single experiment. As these measurements are currently conducted separately, on replicate formulations, results can often be subjective and difficult to correlate. Hence, the aim of the present study was to develop a new AFM-based single-entity ex vivo muco-dissolution (MUCO-DIS) technique to simultaneously evaluate mucoadhesion force, 3D surface topography, polymer dissolution and drug release characteristics. To demonstrate the potential of the current technique, the interactions between model pectin microparticles containing metformin HCl and a range of gastrointestinal mucosal surfaces (gastric, small intestine, large intestine and buccal) were studied. This novel system has not only successfully determined the mucoadhesion force, polymer dissolution and drug release information but has also highlighted the difference in microparticle performance with different mucosal targets. The current work has highlighted the potential of this newly developed MUCO-DIS system and we believe this will be a valuable tool for characterising these popular pharmaceutical formulations. This technique could also provide an opportunity to other scientific fields to evaluate materials, substrate behaviour and their interactions in their hydrated state at nanoscale with real-time chemical and surface mapping.


Assuntos
Absorção Intestinal , Microscopia de Força Atômica/métodos , Membrana Mucosa , Nanotecnologia/métodos , Adesividade , Animais , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Excipientes , Técnicas In Vitro , Metformina/administração & dosagem , Metformina/química , Nanopartículas , Solubilidade , Suínos
5.
PLoS One ; 15(5): e0233013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413086

RESUMO

Global trade and climate change are re-shaping the distribution map of pandemic pathogens. One major emerging concern is Xylella fastidiosa, a tropical bacterium recently introduced into Europe from America. In last decades, X. fastidiosa was detected in several European countries. X. fastidiosa is an insect vector-transmitted bacterial plant pathogen associated with severe diseases in a wide range of hosts. X. fastidiosa through a tight coordination of the adherent biofilm and the planktonic states, invades the host systemically. The planktonic phase is correlated to low cell density and vessel colonization. Increase in cell density triggers a quorum sensing system based on mixture of cis 2-enoic fatty acids-diffusible signalling factors (DSF) that promote stickiness and biofilm. The lipidome profile of Olea europaea L. (cv. Ogliarola salentina) samples, collected in groves located in infected zones and uninfected zones was performed. The untargeted analysis of the lipid profiles of Olive Quick Decline Syndrome (OQDS) positive (+) and negative (-) plants showed a clustering of OQDS+ plants apart from OQDS-. The targeted lipids profile of plants OQDS+ and OQDS- identified a shortlist of 10 lipids that increase their amount in OQDS+ and X. fastidiosa positive olive trees. These lipid entities, provided to X. fastidiosa subsp. pauca pure culture, impact on the dual phase, e.g. planktonic ↔ biofilm. This study provides novel insights on OQDS lipid hallmarks and on molecules that might modulate biofilm phase in X. fastidiosa subsp. pauca.


Assuntos
Metabolismo dos Lipídeos , Olea/metabolismo , Olea/microbiologia , Doenças das Plantas/microbiologia , Xylella/fisiologia , Xylella/patogenicidade , Adesividade , Animais , Biofilmes/crescimento & desenvolvimento , Interações entre Hospedeiro e Microrganismos/fisiologia , Insetos Vetores/microbiologia , Itália , Lipidômica , Percepção de Quorum/fisiologia
6.
Proc Biol Sci ; 287(1926): 20200123, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32370666

RESUMO

Remarkable progress has been made characterizing one of nature's most integrated, hierarchical structures--the fibrillar adhesive system of geckos. Nonetheless, we lack an understanding of how multiple toes coordinate to facilitate geckos' acrobatic locomotion. Here, we tested the control function of gecko toes by running them on vertical substrates varying in orientation, friction and roughness. Sideways wall-running geckos realigned the toes of their top feet upward to resist gravity. Toe contact area was not compromised, but redistributed. Geckos aligned all toes upward to resist slipping when encountering low-friction patches during sideways wall-running. Negotiation of intermittent slippery strips showed an increased contribution of particular toes to compensate for toes that lost adhesion. Increasing substrate roughness using discrete rods perpendicular to sideways locomotion resulted in geckos bending and/or rotating toes to conform to and even grasp the rods, with potential forces more than five times body weight. Geckos increase their effectiveness of manoeuvrability in demanding environments by taking advantage of the distributed control afforded by multiple toes. Our findings provide insight on biological attachment and offer inspiration to advance gecko-inspired robotics and other biomimetic applications.


Assuntos
Lagartos/anatomia & histologia , Dedos do Pé , Adesividade , Animais , Fenômenos Biomecânicos , Fricção , Lagartos/fisiologia , Locomoção , Modelos Biológicos , Corrida , Propriedades de Superfície
7.
Eur J Pharm Sci ; 141: 105115, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654755

RESUMO

In this study, we present the development of spray-dried pectin/hypromellose microspheres as efficient melatonin carrier for targeted nasal delivery. Different pectin to hypromellose weight ratios in the spray-dried feed were employed (i.e. 1:0, 3:1, 1:1 and 1:3) in order to optimise microsphere physicochemical properties influencing overall powder behaviour prior, during and upon nasal delivery. All microspheres assured complete melatonin entrapment and increased dissolution rate in relation to pure melatonin powder. Among all combinations tested, combining pectin with hypromellose at 1:3 wt ratio resulted in the microspheres with the highest potential for melatonin nasal delivery as they assured highest swelling ability and most prominent mucoadhesive properties. Studies on deposition profile revealed adequate turbinate and olfactory deposition of microsphere/lactose monohydrate powder blend administered nasally using MIAT® device, complementing findings relevant for their therapeutic potential. In conclusion, developed microspheres bear the potential to ensure prolonged melatonin retention at the nasal mucosa, improved bioavailability and advanced therapeutic outcome.


Assuntos
Derivados da Hipromelose , Melatonina , Microesferas , Mucosa Nasal/metabolismo , Pectinas , Adesividade , Administração Intranasal , Liberação Controlada de Fármacos , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/química , Melatonina/administração & dosagem , Melatonina/química , Modelos Biológicos , Mucosa Nasal/química , Pectinas/administração & dosagem , Pectinas/química
8.
Carbohydr Polym ; 229: 115506, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826394

RESUMO

In this study, insulin-loaded nanoparticles (NPs) were prepared via self-gelation method using chitosan and aqueous soluble snail mucin as natural polymers. Herein, mucins were ionically interacted with chitosan at different concentrations to obtained insulin-loaded NPs, labelled as A1 (1:1) (i.e., chitosan 2 % w/v + mucin 2 % w/v) and A2 (2:1) (chitosan 4 % w/v + mucin 2 % w/v), using poloxamer and poly vinyl alcohol as solid surfactant. Such formulation was selected to provide the necessary dynamics for the formation of the nanoparticles while maintaining the surface properties that will favor the encapsulation of insulin. Each system was characterized in terms of their particle size distribution, morphology, zeta potential, and polydispersity index. In vitro release of insulin was evaluated in acidic solution (pH 1.2) and phosphate buffer solution (pH 7.4), and the hypoglycaemic activity was evaluated in diabetes rats. The prepared insulin-loaded NPs displayed particles with relatively smooth surfaces and an average particle size of 479.6 and 504.1 nm for A1 and A2, respectively. Zeta potential and polydispersity index, ranged from 22.1 to 31.2 mV and 0.155-0.185, respectively. The encapsulating efficiency for the systems A1 and A2 were 88.6 and 92.5, respectively, and a self-sustained release of encapsulated insulin was observed for over a period of 8 h. In vivo studies revealed a pronounced hypoglycaemic effect in diabetic rats after peroral administration of the insulin-loaded NPs compared to the effect caused by free oral insulin solution. In addition, both the pharmacokinetic and toxicity results showed low plasma clearance of insulin and no signs of toxicity on the liver enzyme and cell viability, which suggested good biocompatibility of the NPs formulations. Overall, the formation of NPs of insulin with chitosan and snail mucin represents a potentially safe and promising approach to protect insulin and enhance its peroral delivery.


Assuntos
Quitosana/química , Diabetes Mellitus/tratamento farmacológico , Portadores de Fármacos/química , Insulina/química , Mucinas/química , Membrana Mucosa/química , Nanopartículas/química , Adesividade , Administração Oral , Animais , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Feminino , Insulina/administração & dosagem , Insulina/uso terapêutico , Masculino , Ratos , Ratos Wistar
9.
Carbohydr Polym ; 229: 115508, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826471

RESUMO

Oral administration of nanoparticles is extremely limited due to the two processes of mucus permeation and epithelial absorption, which requires completely opposite surface properties of the nanocarriers. To tackle the contradiction, we developed a rational strategy to modify the surface of mesoporous carbon nanoparticles with chitosan concealed by a hydrophilic N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) layer. Probucol (PB) with the low poor permeability and solubility was loaded in optimal nanocarriers to realize the high loading efficacy and controlled release. The pHPMA polymer is a hydrophilic "mucus-inert" material, which could be dissociable from the surface of nanoparticles in the mucus, thus promoting their mucus permeation and causing exposure of chitosan in transepithelial transport. The swelling effect of chitosan under acidic conditions allowed regulation of PB release behavior. In conclusion, the mucus-permeable nanocarrier could effectively overcome multiple gastrointestinal absorption barriers and the oral bioavailability of PB-loaded HCMCN was 2.76-fold that of commercial preparation.


Assuntos
Carbono/química , Portadores de Fármacos/química , Nanopartículas/química , Polímeros/química , Probucol/química , Probucol/farmacocinética , Adesividade , Administração Oral , Animais , Disponibilidade Biológica , Portadores de Fármacos/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Masculino , Teste de Materiais , Camundongos , Membrana Mucosa/química , Porosidade , Probucol/administração & dosagem
10.
J Pharm Biomed Anal ; 177: 112852, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31499432

RESUMO

The effect of insertion of SH and S-protected groups on the binding and mucoadhesion properties of quaternary ammonium-chitosans and their nanoparticulate forms has been investigated by NMR spectroscopy. Diclofenac sodium salt has been assumed as low molecular weight probe to detect the different binding behaviour of polymeric materials; mucin from bovine submaxillary glands was selected as the model protein for differentiating their mucoadhesion. NMR proton selective relaxation rates of the probe molecule were remarkably sensitive to the presence of very low amounts of sulfurated moieties. Impact of supramolecular aggregation in nanostructured species was demonstrated as well as the relevance of S-protection.


Assuntos
Diclofenaco/administração & dosagem , Portadores de Fármacos/química , Membrana Mucosa/metabolismo , Nanopartículas/química , Adesividade , Animais , Bovinos , Quitosana/química , Quitosana/metabolismo , Portadores de Fármacos/metabolismo , Peso Molecular , Mucinas/metabolismo , Nanopartículas/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/metabolismo , Enxofre/química
11.
Braz Oral Res ; 33: e111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800863

RESUMO

The aim of the present study was to evaluate the microtensile bond strength and the microleakage of a bulk-fill composite resin compared with a conventional incremental composite resin, in permanent molars and under cariogenic challenge using a Streptococcus mutans model. Permanent human third molars (n = 60) with an occlusal cavity of 5×3×2 mm were randomly allocated into four subgroups of restorative treatments: conventional composite resin with (n = 15) and without (n = 15) cariogenic challenge (Z350-E and Z350-C experimental and control groups, respectively), and bulk-fill composite resin with (n = 15) and without (n = 15) cariogenic challenge (Bulk Fill-E and Bulk Fill-C, respectively). Ten specimens from each subgroup were submitted to microtensile strength, and 5, to microleakage. The cariogenic challenge was conducted using the Streptococcus mutans strain (ATCC) for 7 days. The stickers obtained (1 × 1 × 2 mm) were submitted to a microtensile strength test, followed by classification of the fracture mode. Microleakage was performed using a scoring system. The data were analyzed by Kruskal-Wallis and Mann-Whitney tests (p < 0.05). Filtek Z350 XT resin presented higher microtensile bond strength than Bulk Fill resin without (19.02 ± 4.90 and 8.76 ± 3.94MPa, respectively; p < 0.001) and with cariogenic challenge (22.69 ± 7.86 and 13.31 ± 3.38MPa, respectively; p < 0.02). Z350-C and Bulk Fill-C resins presented a higher prevalence of mixed fractures (23 and 14%, respectively) in the specimens submitted to cariogenic challenge than those of the control groups, whereas microleakage was similar (p = 0.85). The conventional composite resin had higher microtensile bond strength than the bulk-fill resin, but both resin types had similar adhesion quality and microfiltration scores.


Assuntos
Biofilmes/efeitos dos fármacos , Resinas Compostas/química , Colagem Dentária/métodos , Streptococcus mutans/efeitos dos fármacos , Adesividade , Cárie Dentária , Esmalte Dentário/efeitos dos fármacos , Infiltração Dentária , Restauração Dentária Permanente/métodos , Humanos , Teste de Materiais , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Propriedades de Superfície , Resistência à Tração/efeitos dos fármacos , Fatores de Tempo
12.
Mar Drugs ; 17(12)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31835313

RESUMO

Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and seem to be a very promising alternative to conventional oral formulations. Hence, in this study, mucoadhesive buccal films based on the alginate and its oligosaccharide oligomer composed predominantly of mannuronic acid for the administration of posaconazole-antifungal drug from the azole group were developed. As the polymer gelation method, a relatively new freeze-thaw technique was chosen. All prepared formulations were examined for pharmaceutical tests, swelling, mechanical, and mucoadhesive properties. In addition, the influence of sodium alginate (ALG) and alginate oligosaccharides (OLG) on POS antifungal activity on Candida species was performed. It was observed that film formulation containing 1% ALG and 1% OLG (F2) was characterized by optimal mucoadhesive and swelling properties and prolonged drug release up to 5 h. Additionally, it was shown that OLG affected the growth reduction of all tested Candida spp. The obtained data has opened the way for future research for developing OLG-based dosage forms, which might increase the activity of antifungal drugs.


Assuntos
Alginatos/química , Antifúngicos/administração & dosagem , Oligossacarídeos/química , Triazóis/administração & dosagem , Adesividade , Administração Bucal , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Mucosa Bucal/metabolismo , Polímeros/química , Triazóis/farmacologia
13.
Soft Matter ; 15(48): 9942-9948, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31750506

RESUMO

Silica nanoparticles can be used as an adhesive for hydrogels or biological tissues due to their physical adsorption to polymer chains. Recently, we found that mesoporous nanoparticles were able to enhance the adhesion energy between hydrogels compared with non-porous nanoparticles because of the higher outer surface area of mesoporous silica nanoparticles. However, even in the case that the outer surface areas of mesoporous silica nanoparticles are similar, mesoporous nanoparticles with larger pore diameters showed significantly higher nanoparticle-mediated adhesion energy between hydrogels with a swelling ratio of 400%. Here, we have changed the swelling ratio of hydrogels in the preparation step so that the blob size in the polymer network changed accordingly. In experimental data, we found that the optimum pore size of mesoporous nanoparticles increased as the blob size increased for higher swelling ratio, which is ascribed to the larger blob size of polymer networks in hydrogels.


Assuntos
Acrilamidas/química , Hidrogéis/química , Nanopartículas/química , Dióxido de Silício/química , Adesividade , Adsorção , Porosidade
14.
Nanoscale ; 11(47): 22636-22663, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755511

RESUMO

Wettability is a special character found in nature, including the superhydrophobicity of lotus leaves, the underwater superoleophobicity of fish scales and the slipperiness of pitcher plants. These surfaces exhibit unique properties such as resistance to icing, corrosion, and the like. The antifouling properties of the material surface have important applications in a variety of areas, such as in hulls, in medical equipment, in water pipes and underwater equipment. However, the traditional anti-fouling surface is usually combined with toxic substances or its manufacturing process is complicated and expensive, which cannot meet the current antifouling demand. These wettable surfaces have always exhibited good anti-biofouling and self-cleaning properties, and their use as antifouling surfaces can well solve the problems of the above-mentioned traditional antifouling surfaces. Here, we divided the wettable surfaces into superhydrophobic surfaces, underwater superoleophobic surfaces and slippery surfaces, respectively, summarizing their development in the field of antifouling. Their research progress in antibacterial, antibiotic flocculation and antiplatelet adhesion is highlighted. Furthermore, we provide our own insights into the shortcomings and development prospects of wettable surface applications in the field of antifouling.


Assuntos
Incrustação Biológica/prevenção & controle , Molhabilidade , Adesividade , Adsorção , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biomiméticos , Adesão Celular , Desinfetantes/química , Géis/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Células NIH 3T3 , Adesividade Plaquetária , Propriedades de Superfície , Água/química
15.
Int J Pharm ; 572: 118833, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715363

RESUMO

Different types of in-situ forming implants based on poly(lactic-co-glycolic acid) (PLGA) for the controlled dual release of an antiseptic drug (chlorhexidine) and an anti-inflammatory drug (ibuprofen) were prepared and thoroughly characterized in vitro. N-methyl-pyrrolidone (NMP) was used as water-miscible solvent, acetyltributyl citrate (ATBC) as plasticizer and hydroxypropyl methylcellulose (HPMC) was added to enhance the implants' stickiness/bioadhesion upon formation within the periodontal pocket. Different drug forms exhibiting substantially different solubilities were used: chlorhexidine dihydrochloride and digluconate as well as ibuprofen free acid and lysinate. The initial drug loadings were varied from 1.5 to 16.1%. In vitro drug release, dynamic changes in the pH of the surrounding bulk fluid and in the systems' wet mass as well as polymer degradation were monitored. Importantly, the release of both drugs, chlorhexidine and ibuprofen, could effectively be controlled simultaneously during several weeks. Interestingly, the tremendous differences in the drug forms' solubilities (e.g., factor >5000) did not translate into major differences in the resulting release kinetics. In the case of ibuprofen, this can likely (at least in part) be attributed to significant drug-polymer interactions (ibuprofen acts as a plasticizer for PLGA). In the case of chlorhexidine, the release of the much less soluble dihydrochloride was even faster compared to the more soluble digluconate (when combined with ibuprofen free acid). In the case of ibuprofen, at higher initial drug loadings also limited solubility effects within the implants seem to play a role, in contrast to chlorhexidine. In the latter case, instead, increased system porosity effects likely dominate at higher drug loadings.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Clorexidina/administração & dosagem , Ibuprofeno/administração & dosagem , Adesividade , Anti-Infecciosos Locais/química , Anti-Inflamatórios não Esteroides/química , Química Farmacêutica , Clorexidina/química , Preparações de Ação Retardada , Combinação de Medicamentos , Implantes de Medicamento , Liberação Controlada de Fármacos , Excipientes/química , Ibuprofeno/química , Doenças Periodontais/tratamento farmacológico , Plastificantes/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porosidade , Solubilidade , Solventes/química
16.
Commun Biol ; 2: 395, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31701024

RESUMO

DJ-1 is a deglycase enzyme which exhibits a redox-sensitive chaperone-like activity. The partially oxidized state of DJ-1 is active in inhibiting the aggregation of α-synuclein, a key protein associated with Parkinson's disease. The underlying molecular mechanism behind α-synuclein aggregation inhibition remains unknown. Here we report that the partially oxidized DJ-1 possesses an adhesive surface which sequesters α-synuclein monomers and blocks the early stages of α-synuclein aggregation and also restricts the elongation of α-synuclein fibrils. DJ-1 remodels mature α-synuclein fibrils into heterogeneous toxic oligomeric species. The remodeled fibers show loose surface topology due to a decrease in elastic modulus and disrupt membrane architecture, internalize easily and induce aberrant nitric oxide release. Our results provide a mechanism by which partially oxidized DJ-1 counteracts α-synuclein aggregation at initial stages of aggregation and provide evidence of a deleterious effect of remodeled α-synuclein species generated by partially oxidized DJ-1.


Assuntos
Proteína Desglicase DJ-1/metabolismo , alfa-Sinucleína/metabolismo , Adesividade , Amiloide/química , Amiloide/metabolismo , Linhagem Celular , Módulo de Elasticidade , Humanos , Técnicas In Vitro , Microscopia de Força Atômica , Modelos Moleculares , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Neurotoxinas/química , Neurotoxinas/metabolismo , Oxirredução , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Agregados Proteicos , Proteína Desglicase DJ-1/química , alfa-Sinucleína/química
17.
Nature ; 575(7781): 169-174, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31666696

RESUMO

Two dry surfaces can instantly adhere upon contact with each other through intermolecular forces such as hydrogen bonds, electrostatic interactions and van der Waals interactions1,2. However, such instant adhesion is challenging when wet surfaces such as body tissues are involved, because water separates the molecules of the two surfaces, preventing interactions3,4. Although tissue adhesives have potential advantages over suturing or stapling5,6, existing liquid or hydrogel tissue adhesives suffer from several limitations: weak bonding, low biological compatibility, poor mechanical match with tissues, and slow adhesion formation5-13. Here we propose an alternative tissue adhesive in the form of a dry double-sided tape (DST) made from a combination of a biopolymer (gelatin or chitosan) and crosslinked poly(acrylic acid) grafted with N-hydrosuccinimide ester. The adhesion mechanism of this DST relies on the removal of interfacial water from the tissue surface, resulting in fast temporary crosslinking to the surface. Subsequent covalent crosslinking with amine groups on the tissue surface further improves the adhesion stability and strength of the DST. In vitro mouse, in vivo rat and ex vivo porcine models show that the DST can achieve strong adhesion between diverse wet dynamic tissues and engineering solids within five seconds. The DST may be useful as a tissue adhesive and sealant, and in adhering wearable and implantable devices to wet tissues.


Assuntos
Adesividade , Adesivos/química , Coração , Pulmão , Próteses e Implantes , Estômago , Molhabilidade , Resinas Acrílicas/química , Animais , Quitosana/química , Reagentes para Ligações Cruzadas/química , Dessecação , Gelatina/química , Coração/anatomia & histologia , Hidrogéis/química , Ligação de Hidrogênio , Pulmão/anatomia & histologia , Pulmão/química , Camundongos , Ratos , Eletricidade Estática , Estômago/anatomia & histologia , Estômago/química , Suínos , Fatores de Tempo , Água/análise , Água/química , Dispositivos Eletrônicos Vestíveis
18.
J Plant Physiol ; 243: 153054, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31648109

RESUMO

Adhesion of the barley husk to the underlying caryopsis requires the development of a cuticular cementing layer on the caryopsis surface. Differences in adhesion quality among genotypes have previously been correlated with cementing layer composition, which is thought to influence caryopsis cuticle permeability, the hypothesised mechanism of adhesion mediation. It is not yet known whether differences in adhesion quality among genotypes are determined by changes in caryopsis cuticle permeability. We examined changes in candidate cementing layer biosynthetic and regulatory genes to investigate the genetic mechanisms behind husk adhesion quality. We used both commercially relevant UK malting cultivars and older European lines to ensure phenotypic diversity in adhesion quality. An ethylene responsive transcription factor (NUD) is required for the development of the cementing layer. To examine correlations between gene expression, cementing layer permeability and husk adhesion quality we also treated cultivars with ethephon (2-chloroethylphosphonic acid) which breaks down to ethylene, and silver thiosulphate which inhibits ethylene reception, and measured caryopsis cuticle permeability. Differential adhesion qualities among genotypes are not determined by NUD expression during development of the cementing material alone, but could result from differences in biosynthetic gene expression during cementing layer development in response to longer-term NUD expression patterns. Altered caryopsis cuticle permeability does result in altered adhesion quality, but the correlation is not consistently positive or negative. Cuticle permeability is therefore not the mechanism that determines husk adhesion quality, but is likely a consequence of the required cuticular compositional changes that determine adhesion.


Assuntos
Etilenos/metabolismo , Hordeum/fisiologia , Compostos Organofosforados/farmacologia , Reguladores de Crescimento de Planta/farmacologia , Sementes/fisiologia , Tiossulfatos/farmacologia , Adesividade , Etilenos/antagonistas & inibidores , Expressão Gênica/fisiologia , Hordeum/genética , Permeabilidade , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Curr Drug Deliv ; 16(9): 862-871, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633475

RESUMO

BACKGROUND: Nimodipine is a calcium channel blocker frequently used in critical care settings. It is mainly absorbed in the upper gastrointestinal tract. Accordingly, the development of gastroretentive formulation will be beneficial. The benefit would be maximized for critical care patients if the developed system was in liquid form to facilitate the administration through nasogastric tubing. OBJECTIVE: Development of gastro-retentive liquid oral controlled release formulation of nimodipine through in situ gellation. METHODS: Nimodipine dissolution was improved by solid dispersion (SD) using poloxamer 407. Sodium alginate solutions (1, 1.5 and 2%w/v) were loaded with the optimized SD microparticles. Carboxymethylcellulose was added to modulate the release and to augment mucoadhesion power. All in situ gelling alginate solutions were characterized regarding viscosity, gelling capacity and drug release. SD microparticles showed considerable improvement in nimodipine dissolution. RESULTS: All alginate systems were pourable. Increasing alginate concentration increased the gelling capacity and reduced drug release rate. The addition of carboxymethylcellulose produced greater control over drug release rate. X-ray radiography showed successful stomach-retention over 8 hours in rabbits, which correlates with the controlled release pattern of the developed systems. CONCLUSION: The study provides the formulator with a range of gastroretentive controlled release formulations of nimodipine while maintaining the convenience of administration through nasogastric tubing with the potential for enhanced bioavailability.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Sistemas de Liberação de Medicamentos , Nimodipina/administração & dosagem , Adesividade , Administração Oral , Alginatos/administração & dosagem , Alginatos/química , Animais , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacocinética , Carboximetilcelulose Sódica/administração & dosagem , Carboximetilcelulose Sódica/química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Mucosa Gástrica/metabolismo , Masculino , Nimodipina/química , Nimodipina/farmacocinética , Poloxâmero/administração & dosagem , Poloxâmero/química , Coelhos
20.
Dent Mater ; 35(12): 1750-1756, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31610888

RESUMO

OBJECTIVE: This in vitro study was designed to evaluate the biocompatibility, adhesiveness, and antimicrobial activity of epoxy resin-based sealer associated with N-Acetylcysteine (NAC) or beta-tricalcium phosphate nanoparticles (ß-TCP) as an experimental retro-filling material. METHODS: Cytotoxicity was assessed using 2,3-Bis-(Methoxy-4-Nitro-5-Sulphophenyl)-2H-Tetrazolium-5-Carboxanilide (XTT) and Sulforhodamine B (SRB) assays after exposing human periodontal ligament fibroblasts to extracts of the materials for 1, 3, or 7 days. For the adhesive resistance test, root canals (48 single-root teeth) were instrumented with Reciproc #40 files (VDW GmbH, Germany) and obturated. After 7 days, the apices were sectioned and a retrograde cavity prepared and filled with the experimental materials (Mineral trioxide aggregate, Epoxy sealer, Epoxy sealer+NAC, and Epoxy sealer+ß-TCP). For the push-out test, one 2-mm thick slice was obtained from the apical third of each specimen. Antimicrobial activity was performed using agar diffusion method. Biofilms were grown in microplates and exposed to the extracts of retro-filled materials, followed by analysis of growth inhibition on agar plates. RESULTS: Epoxy sealer in association with ß-TCP or NAC showed better bond strength while Mineral trioxide aggregate allowed for the lowest adhesion. Mineral trioxide aggregate, Epoxy sealer+ß-TCP, and Epoxy sealer+NAC showed low cytotoxicity. Epoxy sealer was the most cytotoxic. In antimicrobial activity assays, all materials had no effect on Candida albicans. Addition of NAC improved the antimicrobial property of Epoxy sealer against Enterococcus faecalis compared to unmodified Epoxy sealer (P<0.05). SIGNIFICANCE: Incorporating ß-TCP or NAC with Epoxy sealer could improve the adhesiveness and biocompatibility for better use in endodontic therapy.


Assuntos
Colagem Dentária , Materiais Restauradores do Canal Radicular , Acetilcisteína , Adesividade , Fosfatos de Cálcio , Cavidade Pulpar , Dentina , Resinas Epóxi , Humanos , Teste de Materiais
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