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Objective: To enhance the blood-brain barrier (BBB) penetration and glioma targeting ability of arsenic trioxide (As2O3), the lipid-coated mesoporous silica nanoparticles (MSN) modified with Angiopep-2 and polyacrylic acid (ANG-PAA-LP-MSN) is prepared by thin-film hydration method. This complex is specifically recognized and bound between ANG and low-density lipoprotein receptor-related protein-1 (LRP-1) which is highly expressed on BBB and glioma cells. Methods: The drug delivery system characterization were analysed by transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). Dialysis bag method was used to analyse the drug release characteristics at different pH conditions (pH 6.0 and 7.4, respectively). Cytotoxicity of nanocarriers and the antitumor activity in vitro of this drug delivery system were measured on human brain micro-capillary endothelial cells (HBMEC) and glioma cells (C6) by MTT assay. Moreover, in vitro cells model of BBB was established to study the effect of vehicle on the transmembrane transport of As2O3. Results: The drug delivery system (ANG-PAA-LP-MSN@As2O3) was constructed successfully, it showed a rounded "core-shell" structure with good dispersibility and stability. The drug loading efficency was 6.32%. After PAA modification, this drug delivery system showed higher pH responsiveness to release medium, and the burst release of As2O3 was significantly reduced compared with that of unmodified group. Lipid coating could significantly improve the biosafety and penetration ability of BBB. The antitumor activity study showed that ANG-PAA-LP-MSN@As2O3 exhibited an ideal glioma inhibition effect in vitro. Conclusion: This smart targeting drug delivery system enhance the BBB penetration ability of As2O3, and the special pH responsiveness demonstrated antitumor ability through increasing its accumulation in the tumor site.
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Polyacrylic acid was firstly grafted by N-amino-4-N-methylpiperazine-1,8-naphthlimide (AMN) to prepare a amphiphilic polymer, which was self-assembled in water producing nanoparticles called as PAAMN.Then the morphology, structure and fluorescence properties of PAAMN were investigated by various methods including transmission electron microscopy, dynamic light scattering, ultraviolet-visible spectroscopy (UV-Vis), nuclear magnetic resonance spectroscopy (HNMR) and fluorescence spectroscopy.MTT assay was carried out to assess the cell compatibility of PAAMN.Finally, the fluorescence from PAAMN self and HeLa cells incubated with PAAMN was observed by fluorescence microscope.The results revealed that PAAMN had spherical structure, in which naphthlimide fluorphores were immobilized in the polyacrylic acid matrix with the degree of substitution of 4.1%.Under the physiological pH condition, PAAMN excited at 390 nm could emit strong and stable fluorescence at 534 nm.In the range of pH 4.0-10.0, its excitation and emission wavelengths had no obvious change.The fluorescence intensity of PAAMN increased with the decrease of pH values, but the pH sensitivity of PAAMN was much lower than that of AMN.PAAMN had good cell compatibility.From the pictures of fluorescence imaging, it was found that both PAAMN self and cells-engulfed PAAMN could emit green fluorescence upon excited at 390 nm, indicating the potential of the developed nanoparticle for cell imaging.
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OBJECTIVE@#To determine the antileishmanial vaccine effectiveness of lipophosphoglycan (LPG) and polyacrylic acids (PAA) conjugates on in vivo mice models.@*METHODS@#LPG molecule was isolated and purified from large-scale Leishmania donovani parasite culture. Protection efficacies of LPG alone, in combination with Freund's adjuvant, in a physical mixture and in conjugate (consisting of various LPG concentrations) with PAA, were comparatively determined by various techniques, such as cultivation with the micro-culture method, assessment of in vitro infection rates of peritoneal macrophages, determination of parasite load in liver with Leishman-Donovan Units, and detection of cytokine responses.@*RESULTS@#Obtained results demonstrated that the highest vaccine-mediated immune protection was provided by LPG-PAA conjugate due to all parameters investigated. According to the Leishman-Donovan Units results, the sharpest decline in parasite load was seen with a ratio of 81.17% when 35 μg LPG containing conjugate was applied. This value was 44.93% for the control group immunized only with LPG. Moreover, decreases in parasite load were 53.37%, 55.2% and 65.8% for the groups immunized with 10 μg LPG containing LPG-PAA conjugate, a physical mixture of the LPG-PAA, and a mixture of LPG + Freund's adjuvant, respectively. Furthermore, cytokine results supported that Th1 mediated protection occurred when mice were immunized with LPG-PAA conjugate.@*CONCLUSIONS@#It has been demonstrated in this study that conjugate of LPG and PAA has an antileishmanial vaccine effect against visceral leishmaniasis. In this respect, the present study may lead to new vaccine approaches based on high immunogenic LPG molecule and adjuvant polymers in fighting against Leishmania infection.
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Objective To determine the antileishmanial vaccine effectiveness of lipophosphoglycan (LPG) and polyacrylic acids (PAA) conjugates on in vivo mice models. Methods LPG molecule was isolated and purified from large-scale Leishmania donovani parasite culture. Protection efficacies of LPG alone, in combination with Freund's adjuvant, in a physical mixture and in conjugate (consisting of various LPG concentrations) with PAA, were comparatively determined by various techniques, such as cultivation with the micro-culture method, assessment of in vitro infection rates of peritoneal macrophages, determination of parasite load in liver with Leishman-Donovan Units, and detection of cytokine responses. Results Obtained results demonstrated that the highest vaccine-mediated immune protection was provided by LPG-PAA conjugate due to all parameters investigated. According to the Leishman-Donovan Units results, the sharpest decline in parasite load was seen with a ratio of 81.17% when 35 μg LPG containing conjugate was applied. This value was 44.93% for the control group immunized only with LPG. Moreover, decreases in parasite load were 53.37%, 55.2% and 65.8% for the groups immunized with 10 μg LPG containing LPG-PAA conjugate, a physical mixture of the LPG–PAA, and a mixture of LPG + Freund's adjuvant, respectively. Furthermore, cytokine results supported that Th1 mediated protection occurred when mice were immunized with LPG-PAA conjugate. Conclusions It has been demonstrated in this study that conjugate of LPG and PAA has an antileishmanial vaccine effect against visceral leishmaniasis. In this respect, the present study may lead to new vaccine approaches based on high immunogenic LPG molecule and adjuvant polymers in fighting against Leishmania infection.
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El objetivo de este estudio fue valorar la microfiltración del ionómero de vidrio mejorado (Ketac Molar Easymix ®) con o sin el uso de acondicionador. Para lograr éste, se seleccionaron 40 terceros molares extraídos, limpios e hidratados. Se formaron dos grupos de 20 muestras de forma aleatoria, a los cuales se les realizó profilaxis y cavidades de clase V sobre la cara vestibular. Al grupo A se le colocó un acondicionador de ácido poliacrílico como indica el fabricante, antes del ionómero, y al grupo B se le colocó el ionómero directamente. Las muestras se sometieron a un proceso de termociclado y fueron sumergidas en azul de metileno al 1%, durante 30 minutos. Cada molar fue seccionado con disco de carburo, con cortes longitudinales en el centro de la preparación. Cada sección fue examinada minuciosamente al microscopio. Se calificaron las muestras y se obtuvo que el promedio de microfiltración para el grupo A fue de 2.06% y para el grupo B fue de 1.84%, sin representar diferencias significativas. Por lo que se concluye, con que no existen diferencias significativas en colocar acondicionador en este tipo de cavidades y con este material en particular.
The aim of the present study was to assess microleakage experienced by improved glass ionomer (Ketac Molar Easymix ®) with and without use of conditioner. In order to conduct this study, 40 third molars were used. Molars had previously been extracted, cleansed and hydrated. Two 20 randomly selected sample groups were established. Samples were subjected to prophylaxis and class V cavities were created on the vestibular (labial) surface of the teeth. Before ionomer application, and according to manufacturer's instructions, group A received a polyacrylic acid conditioner, whereas group B received direct ionomer application. All samples were subjected to a thermo-cycling process and then were immersed in a 1% methylene blue solution for 30 minutes. All molars were sectioned with carbide burr executing longitudinal cuts at the preparation's center. Each section was carefully examined under the microscope. Samples were rated and the following was observed: microleakage, for group A was 2.06% and for group B 1.84% which did not represent statistically significant differences. It can therefore be concluded that application of conditioner in this type of cavities and with this particular material does not cause statistically significant differences.
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Objective:To prepare sustained-release pellets of memantine hydrochloride and investigate the in vitro drug release be-havior. Methods:The drug-loaded pellets were prepared by a fluid bed coating technology, the sustained-release pellets were prepared with Eudragit RL 30D and Eudragit RS 30D as the coating materials, and in vitro drug release behavior of the sustained-release pellets was studied. Results:The in vitro drug release was steady and complete in 24h, which fit a zero-order kinetics model. Conclusion:The memantine hydrochloride sustained-release pellets has the sustained-release property.
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Objective: To prepare polyacrylic acid grafted arsenic trioxide-loaded pH-responsive mesoporous silica nanoparticles (PAA-ATO-MSNs) and to investigate their physicochemical properties, in vitro release behavior, and pharmacokinetics in rats. Methods: PAA was covalently attached to the exterior surface of amino group functionalized MSNs prepared by co-condensation method and ATO was loaded into them by electrostatic adsorption. Transmission electron microscope (TEM), small angle X-ray diffraction (SAXRD), nitrogen adsorption, thermogravimetric analysis (TGA), fourier transform infrared (FT-IR) spectra, and laser particle size analyzer were used to determine the physicochemical properties. The entrapment efficiency (EE) and drug loading (DL) of PAA-ATO-MSNs were investigated with the method of high speed centrifugation combined with inductively coupled plasma emission spectrum (ICP). The drug release behavior of PAA-ATO-MSNs was studied using dynamic dialysis method, PBS (pH 5.0, 6.0, and 7.4) chosen as release media. Pharmacokinetic behavior of PAA-ATO-MSNs after iv injection in rats was studied. Results: Morphology of PAA-ATO-MSNs was spherical and the mean particle size, Zeta potential, EE, and DL of PAA-ATO-MSNs were (158.60 ± 1.32) nm, (-28.40 ± 0.34) mV, (40.95 ± 3.21)%, and (11.42 ± 1.75)%, respectively. In vitro release behavior of PAA-ATO-MSNs showed pH-responsive characteristic and the cumulative release amount was increased with the decrease of pH value. Compared with ATO-Sol and ATO-MSNs group, t1/2β was significantly prolonged and AUC was significantly increased (P < 0.01). Conclusion: Release of ATO from PAA-ATO-MSNs showed the obvious pH-responsive characteristic and sustained-release in vitro and PAA-ATO-MSNs could improve the pharmacokinetic behavior in rats. PAA-MSNs might be promising carrier to load ATO for cancer therapy.
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Enzyme stability is critical in biotechnology, pharmaceutical and cosmetic industries. Investigations on this subject have drawn attention because of its practical application. Bromelain is a thiol-endopeptidase, obtained from pineapple (Ananas comosus), known for its clinical and therapeutic applications, particularly to selective burn debridement and improvement of antibiotic action and anti-inflammatory activities. To date, the use of bromelain in pharmacological or industrial applications is limited, due to commercial availability, costs, and sensitivity to pH and temperature. Therefore, a better understanding of enzyme stability would be of great interest. The aim of this study was to evaluate bromelain activity and stability in several pH (2.0 to 8.0) and in polyethylene glycol and polyacrylic acid solutions. We observed that bromelain was able to maintain its stability at pH 5.0 for the temperatures studied. PEG solutions increased bromelain stability, but PAA solutions had the opposite effect.
Estabilidade de enzimas é uma questão fundamental em indústrias biotecnológicas, farmacêuticas e cosméticas. As investigações sobre o assunto têm chamado a atenção por sua aplicação prática. A bromelina é uma tiol-endopeptidase, obtida a partir do abacaxi (Ananas comosus). É conhecida por suas aplicações clínicas e terapêuticas, especialmente para desbridamento seletivo de queimaduras, melhoria de ações antibiótica e de atividades anti-inflamatórias. Até o momento, a utilização da bromelina em aplicações farmacológicas industriais é limitada, devido à disponibilidade comercial, os custos, a sensibilidade ao pH e temperatura. Portanto, a maior compreensão da estabilidade desta enzima seria de grande interesse. O objetivo deste estudo foi avaliar a estabilidade da atividade da bromelina em vários pH (2,0 a 8,0) e em soluções de polietilenoglicol e de ácido poliacrílico. Observamos que a bromelina foi capaz de manter a sua estabilidade em pH 5.0, em todas as temperaturas estudadas. Soluções de PEG aumentaram a estabilidade da bromelina, enquanto que soluções de PAA obtiveram efeito oposto.
Subject(s)
Bromelains/analysis , Alkalinization/adverse effects , Polyethylene Glycols/analysis , Enzyme Stability , EnzymesABSTRACT
Background: Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change. Aim: To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration. Materials and Methods: Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits. Statistical Analysis: Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study. Results: Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained. Conclusions: Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.
Subject(s)
Animals , Drug Delivery Systems , Hydrogels , Hydrogen-Ion Concentration , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/pharmacokinetics , Rabbits , Timolol/administration & dosage , Timolol/pharmacokinetics , ViscosityABSTRACT
Objective: To prepare fluorouracil-loaded chitosan nanoparticle (5-Fu-CS-NP) for ophthalmologic usage and evaluate its releasing characteristics in vitro. Methods: 5-Fu-CS-NP was prepared with 5-Fu, polyacrylic acid and chitosan using dispersion method. The mean size, entrapment efficiency (EE%), drug loading (DL%) and the in vitro releasing characteristics of 5-Fu-CS-NP were investigated. Results and conclusion: The mean size of 5-Fu-CS-NP was (144.6±3.1) nm, the EE% was 84.5% and the DL% was 3.91%. 5-Fu-CS-NP had a satisfactory sustained-releasing effect and the releasing could last for 3-7 days, and the release behavior was not greatly changed within a pH value of 7.2-7.4.
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The purpose of this study was to compare in vitro shear bonding strength with three different enamel surface preparations: (1) 30% sulfated polyacrylic acid with 0.3M lithium sulfate (2) 40% sulfated polyacrylic acid with 0.3M lithium sulfate (3) 37% phosphoric acid. 105 extracted human premolar teeth were divided into each three groups of 35. Metal brackets were bonded to teeth in the three groups. The same self curing resin was used for all groups. A shearing force was applied to the teeth. After debonding, bases of bracket and enamel surfaces were examined under steroscopic microscope to determine the failure modes. Statistical analysis of the data was carried out with one way ANOVA and Student t-test. The results were as follows. 1. Shear bond strength values for the 30% polyacrylic acid and 40% polyacrylic acid group were approximately two thirds of the phosphoric acid group. It maintains clinically acceptable but not enough bond strength. 2. There was no statistically significant difference in shear bond strengths between 30% and 40% polyacrylic acid group. 3. The failure modes of brackets had some differences. In polyacrylic acid groups, the percentage of adhesive/enamel failure was higher than that of adhesive/bracket interface failure. On the contrary in phosphoric acid groups, the results were reversed. Further study of bond strength could be required. If polyacrylic acid enamel conditioning is used clinically.
Subject(s)
Humans , Bicuspid , Dental Enamel , Lithium , ToothABSTRACT
Objective:To prepare fluorouracil-loaded chitosan nanoparticle (5-Fu-CS-NP) for ophthalmologic usage and evaluate its releasing characteristics in vitro. Methods: 5-Fu-CS-NP was prepared with 5-Fu, polyacrylic acid and chitosan using dispersion method. The mean size, entrapment efficiency (EE%), drug loading (DL%) and the in vitro releasing characteristics of 5-Fu-CS-NP were investigated.Results and conclusion: The mean size of 5-Fu-CS-NP was (144.6?3.1) nm, the EE% was 84.5% and the DL% was 3.91%. 5-Fu-CS-NP had a satisfactory sustained-releasing effect and the releasing could last for 3-7 days, and the release behavior was not greatly changed within a pH value of 7.2-7.4.
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The purpose of this study was to compare bracket shear bond strengths of th crystal growth solutions wi those of the 37% phosphoric acid etch technique. The 4 crystal growth solutions were made experimentally in th lab, that is (1)30% polyacrylic acid solution containing 0.3 M sulfuric acid (ES 1), (2)30% polyacrylic acid solution containing 0.6 M solution acid (ES 2), (3)30% polyacrylic acid solution containing 0.3 M solution acid and 0.6M lithium sulfate(ES 3), (4)30% polyacrylic acid solution containing 0.3 M solution acid and 5% phosphoric acid (ES 4). The 37% phosphoric acid solution used as a control. Bovine lower incisor tooth enamel was treated by the above solutions for 60 sec, washed out for 20 sec with slow water stream, and bonded lower anterior edgewise bracket with the light curing orthodontic composit resin adhesives. The teeth bonded brackets were stored in the distilled water at room temperature for 24h, and followed to test the bracket shear bond strength. The acid etch technique showed 177.6kg/cm(2) of mean shear bond strength which was the highest among the enamel treatment solutions. ES 1 shown 58.4 kg/cm(2) of mead shear bond strength and the of ES 4 showed 66.5 kg/cm(2). There was no significant difference between the two(p>0.05). Es 2 showed 110.6kg/cm(2) of mean shear bond strength which was 62.3% of that of acid etch technique. ES 3 showed 131.3kg/cm(2) of mead shear bond strength which was the highest among experimental crystal growth solution and which was 74% of that of acid etch technique. The shear bond strengths of the crystal growth solutions and were significantly lower that that of acid etch technique(p<0.05). The results suggest that bracket shear bond strength of 30% polyacrylic acid solution containing 0.3M sulfuric acid and 0.6M lithium sulfate were showed the highest, it is low for the clinical application of this solution.
Subject(s)
Adhesives , Crystallization , Dental Enamel , Incisor , Lithium , Rivers , Sulfur , Tooth , WaterABSTRACT
The purpose of this study was to compare shear bonding strengths and debonding patterns of the ceramic brackets attached on the crystal which were grown on the enamel surface of a tooth with different concentrations of lithium sulphate-contained polyacrylic acid in different application times. Four kinds of concentrations of mixed solutions were made and applied to the enamel surface on extracted human premolars. The solutions were made by adding 0.3M or 0.6M of lithium sulfate to 50% or 65% of polyacrylic acid with 0.3M sulfuric acid. The solutions were applied for 30 or 60 seconds. After bonding, a universal testing machine was used to measure the shear bond strength, and then observations were made of debonding patterns through the stereoscope. And the enamel surface was observed through the scanning electron microscope to examine the pattern of crystal growth and debonding. The results were as follows: 1, Shear bond strength in the enamel surface treated with 50% polyacrylic acid was higher than that with 65% polyacrylic acid. 2. There were no statistical differences in shear bond strength according to concentration of lithium sulfate and application time of solutions. 3. Enamel surface was almost free of resin debris after debonding. 4. Enamel surface treated with 50% polyacrylic acid showed higher density of crystal growth than that with 65% polyacrylic acid under scanning electron microscope.
Subject(s)
Humans , Bicuspid , Ceramics , Crystallization , Dental Enamel , Lithium , Sulfur , ToothABSTRACT
This study was designed to observe the effects of various concentration of polyacrylic acid containing different concentration of sulfate ion on the crystal formation on the enamel surface. Experimental crystal growth solutions were made of 10/, 20% 30%, and 40% polyacrylic acid(molecnlar weight, 5,000) solutions which containing O.1M, 0.2M, 0.3M, 0.5M, and LOM sulfate ion respectively. The extracted human first bicuspid enamel surface was contacted for 60 seconds with these solutions, washed for 15 seconds, dried, and then the crystal topography on the enamel surface was observed under the scanning electron microscope. The crystal topography were evaluated on the SEM photographs by degree of crystal coverage, crystal length, and consistency of crystal morphology, and conclusions were as the follows. 1. Polyacrylic acid. solution etched slightly the enamel surface, and the difference of etching effect by its concentration was not observed. 2. The effect of concentration of polyacrylic acid on the crystal formation was less, especially that of 20% - 40% polyacrylic? acid was almost not different. 3. Concentration of the sulfate ion was a- determinant factor in precipitating crystals on the enamel. The experimental crystal growth solutions containing 0.1 M sulfate ion did not make crystal formation but those containing over 0.2 M sulfate ion did. 4. The degree of crystal coverage showed a tendency to increase and then decrease according to the concentration of sulfate ion in the 20%-40% polyacrylic acid. The experimental solutions containing 0.5 M sulfate ion showed the peak of degree of crystal coverage. 5. The crystal length showed a tendency to decrease by increment of sulfate ion in the polyacrylic acid solution. 6. There was a tendency to increase the frequency of random arragement of short crystals when increasing the concentration of sulfate ion in the polyacrylic acid solution. The lower concentration of sulfate ion in the polyacrylic acid solutions tended to make spherulitic arrangement of crystals, the higher concentration of sulfate ion, the more random arrangement of crystals. The experimental solutions containing 0.5M sulfate ion showed more spherulitic arrangement than random arrangement of crystals. 7. The best one of these experimental crystal growth solutions was 30% polyacrylic acid solution containing 0.5M sulfate ion.