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In this work, functionalized carbon nanotubes (CNTs) using two polyamine polymers, polyethyleneimine (PEI) and polyamidoamine dendrimer (PAMAM), were investigated by thermal analysis in order to address preparation strategies to obtain low cytotoxic compounds with the ability to conjugate micro-RNAs and, at the same time, to transfect efficiently endothelial cells. Thermogravimetric analysis (TGA) was coupled to chemometrics as a novel analytical strategy to characterize functionalized CNTs from different preparation conditions. In particular, two starting materials were considered:very small CNTs and carboxylated CNTs (CNT-COOH) in order to examine the affinity with polymers. Chemometrics permitted to compare results from TGA and to investigate the effect of a number of factors affecting the synthesis of coated nanotubes including a different amount of involved polymer and the time required for the suspension for a satisfactory and reproducible preparation procedure. The results demonstrated the effectiveness of TGA as a tool able to address synthesis of coated CNTs to be employed as efficient drug delivery vectors in biomedical applications.
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Arsenic trioxide (ATO) is an effective component of traditional Chinese medicine arsenic. The existing studies have shown its good inhibition and apoptosis ability on a variety of tumours. However, its toxicity and difficulties in the permeability into the blood brain barrier (BBB) has the limitation in the application of glioma treatment. Polyamide-amine dendrimer (PAMAM) is a synthetic polymer with many advantages, such as a good permeability, stability and biocompatibility. Additionally, the 5th generation of PAMAM is an ideal drug carrier due to its three-dimensional structure. In this study, the 5th generation of PAMAM co-modified with RGDyC and PEG, then confirmed by ¹H-NMR. The average particle size of nanoparticles was about 20 nm according to the nanoparticle size-potential analyser and transmission electron microscopy. release showed that the nanocarrier not only has the sustained release effect, but also some pH-sensitive properties. The cell results showed that PAMAM co-modified with RGDyC and PEGAM has a lower cytotoxicity than the non-modified group . Accordingly, the drug delivery system has a better anti-tumour effect across the blood brain barrier (BBB) , which further proves the tumour targeting of RGDyC.
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The objective of this work is to evaluate the effect of polyamidoamine (PAMAM) dendrimers on electroosmotic flow (EOF) through skin. The effect of size and concentration of dendrimer was studied, using generation 1, 4 and 7 dendrimer (G1, G4 and G7, respectively). As a marker molecule for the direction and magnitude of EOF, a neutral molecule, acetoaminophen (AAP) was used. The visualization of dendrimer permeation into the current conducting pore (CCP) of skin was made using G4–fluorescein isothiocyanate (FITC) conjugate and confocal microscopy. Without dendrimer, anodal flux of AAP was much higher than cathodal or passive flux. When G1 dendrimer was added, anodal flux decreased, presumably due to the decrease in EOF by the association of G1 dendrimer with net negative charge in CCP. As the generation increased, larger decrease in anodal flux was observed, and the direction of EOF was reversed. Small amount of methanol used for the preparation of dendrimer solution also contributed to the decrease in anodal flux of AAP. Cross-sectional view perpendicular to the skin surface by confocal laser scanning microscope (CLSM) study showed that G4 dendrimer-FITC conjugate (G4-FITC) can penetrate into the viable epidermis and dermis under anodal current. The permeation route seemed to be localized on hair follicle region. These results suggest that PAMAM dendrimers can permeate into CCP and change the magnitude and direction of EOF. Overall, we obtained a better understanding on the mechanistic insights into the electroosmosis phenomena and its role on flux during iontophoresis.
Subject(s)
Acetaminophen , Dendrimers , Dermis , Electroosmosis , Epidermis , Fluorescein-5-isothiocyanate , Hair Follicle , Iontophoresis , Methanol , Microscopy, Confocal , SkinABSTRACT
PAMAM dendrimer is one of the most widely studied dendrimers in recent years, which has a large number of functional groups on the surface and cavities inside, specific three-dimensional structure and good biocompatibility, permeability and stability. It has been widely applied in drug and gene carrier fields and may become a new absorption enhancer. In order to study the absorption enhancing effects of PAMAM dendrimers, liquiritin was selected as the model drug, with the protection of spleen and liver, detoxification and other functions, but it had not been widely used in clinical application because of its difficult absorption, first pass effect, and low bioavailability. This topic was based on the two main determinants (solubility and permeability) of intestinal absorption in the body, researched the physicochemical properties of liquiritin, analyzed the transport volume of liquiritin with or without PAMAM dendrimers by using Caco-2 cell model, and analyzed the cytotoxicity of PAMAM dendrimers on Caco-2 cells by MTT experiments. These results showed that 0.1% of the G4 generation PAG can promote the absorption of liquiritin safely and effectively, and it was suitable for further development into a new type of pharmaceutical excipients.
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OBJECTIVE: To study the effect of different graft ratios of PEG on the toxicity in vitro and cellular uptake of PAMAM G5 dendrimers. METHODS: Nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FT-IR) spectroscopy were used to confirm the structure of PEG-PAMAM G5 dendrimers with four different graft ratios. The particle size and Zeta potential of the nanoparticles were determined by nanoparticle size-Zeta potential analyzer. The toxicity in vitro,cellular uptake, and intracellular localization were tested by hemolysis assay,cytotoxicity assay,cellular uptake test,and laser scanning confocal microscope images,respectively. RESULTS: The particle sizes of dendrimers with PEG graft ratios of 7.8%,14.1%, 20.3%,and 24.2% were (17.05 ± 1.77), (20.77 ± 1.02),(21.68 ± 1.04),and (23.19 ± 0.54) nm,respectively. The Zeta potential decreased from (25.57 ± 1.37) mV of PAMAM G5 to (9.27 ± 0.40) mV of PEG31-PAMAM G5. In addition, the hemolytic toxicity and cytotoxicity of PAMAM G5 dendrimers also markedly decreased especially at high concentrations because of PEG modification. Moreover, the PEG-PAMAM G5 dendrimers with particle diameter of nearly 20 nm not only could be taken in by HBMEC cells, but also accumulated in the cell nucleus. CONCLUSION: Modification of PEG can greatly reduce the toxicity of PAMAM G5 dendrimers in vitro, and the higher the degree of modification, the more obvious is the attenuated effect. The PEG-PAMAM G5 dendrimers with particle diameter larger than 20 nm still can be taken in by HBMEC cells and accumulate in the cell nucleus, which provide a foundation for the further research using modified PEG-PAMAM G5 as a basic carrier for genes and nuclear targeting agents in nano medicine.
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Objective:To evaluate the sealing ability of the 3.0th generation of polyamidoamine dendrimer(3.0 PAMAM)on hu-man dentinal tubules.Methods:1 6 extracted premolars were cut into 2 mm thick dentin slices to establish sensitive dentin model in vitro.Then 2 samples without any treatment were selected randomly into demineralized dentin group,and the remain 1 4 dentine pills were divided into 2 groups by the random number table(n=7).Samples in the experimental group were treated with 3.0 PAMAM, those in the control group were treated with deionized water.After having immersed in the artificial saliva for 2 and 4 weeks respec-tively,the dentin slices were examined by scanning electron microscope(SEM)and X-ray energy dispersive spectroscopy(EDS). Results:SEM showed that the minerals on the surfaces of the dentine disks in experimental group were formed gradually with the time,the dentinal tubules were blocked 4 weeks after treatment.The minerals on the sample surface in control group were less and the dentinal tubules remained open.EDS results showed that Ca/P(1 .49 ±0.1 6)of mineral deposition in the experimental group was higher than that in the control group (1 .1 8 ±0.20)(P<0.05).Conclusion:The 3.0th generation of PAMAMhas the occlu-ding ability by inducing remineralization on the dentine surface and it may be used in the treatment of dentin hypersensitivity.
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Dendrimers are novel synthetic polymeric systems having improved physical and chemical properties due to their unique three dimensional architecture. Dendrimers have a well defined size, shape, molecular weight and monodispersity. These are compatible with drug moieties as well as bioactive molecules like DNA, heparin and other polyanions. The nanoscopic size and recognition abilities make dendrimers as ideal building blocks for self-assembly and self-organization systems. The cavities inside the dendritic structure can be modified to incorporate hydrophobic and hydrophilic drugs. The terminal groups are modified to attach antibodies and bioactive substances for targeting purpose along with providing miscibility, reactivity and solubility. Currently, dendrimers are of great interest for delivering drug molecules via different routes as a nanocarrier. Toxicity problems associated with cationic dendrimers are overcome by PEGylation, which neutralizes the charge on them. Dendrimers possess suitable properties to establish itself as a potential carrier for delivery of therapeutic agents irrespective of certain synthetic and regulatory constraints. This review contains various structural aspects and properties of dendrimers along with their pharmaceutical application as a potential novel drug delivery carrier.
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Objective To construct and evaluate a novel PAMAM dendrimer vector-DNA vaccine for schistosomiasis japonica.Methods Lysine was used to modify 4.0G PAMAM.and the modified product PAMAM-Lys was synthesized.Agarose gel electrophoresis was used to confirm the composite ratio of plasmid DNA and dendrimer.Micrestructure of the compound was observed by using transmission electronic microscopy,and the stability was analyzed by using electrophoresis.The viability of the cells transfected with dendrimers was evaluated by using a MTT technique in vitro.Fiftyty mice were immunized with purified plasmid pJW4303,pJW4303-Sj23 dendrimer PAMAM-Lys and compound PAMAM-Lys/pJW4303-Sj23,respectively.The specific antibodies of the mice in each group were detected to access the immunoreactivity.Results The agarese gel electrophoresis showed that when the charge ratio of the dendrimer vector and DNA was between 2 and 4,the positive and negative charges could be counteraeted completely,and the compound was blocked completely by DNA electrophoresis.The obscrvation results with transmission electronic microscopy showed that the composition of dendrimer vector and DNA caused shrink of DNA structure.Dendrimer-DNA compound had a good stability.MTT showed the modified dendrimer vector and DNA compound system produced a lower cell toxicity on 293T cell than the unmodified Ones.Thk levels of specific antibodies of the mice immunized with PAMAM-Lys/pJW4303Sj23 were significantly higher than those of the mice immunized with naked DNA vaccine(P<0.05).Conclusions The lysinemodified PAMAM-lys is an excellent vector,and has an appropriate biocompatibility.Lysine-modification can reduce the cell toxicity of PAMAM dendrimer significantly.PAMAM-Lys can enhance the immunoreactivity of DNA vacmine which merits further application in schistosomiasis DNA vaccine.
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Objective Polyamidoamine(PAMAM) dendrimers enhance the solubility of nicotinic acid. Methods PAMAM dendrimers of generation 1 to 6 were prepared and the effect of pH and concentration of the dendrimers on the solubility enhancement of nicotinic acid was investigated. Results The pH and concentration of the dendrimers influence the solubility enhancement of nicotinic acid. Conclusions Electrostatic interaction between the carboxyl group of the nicotinic acid and the amine groups of the dendrimers is involved.
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@#ObjectivePolyamidoamine(PAMAM) dendrimers enhance the solubility of nicotinic acid. MethodsPAMAM dendrimers of generation 1 to 6 were prepared and the effect of pH and concentration of the dendrimers on the solubility enhancement of nicotinic acid was investigated. ResultsThe pH and concentration of the dendrimers influence the solubility enhancement of nicotinic acid. Conclusions Electrostatic interaction between the carboxyl group of the nicotinic acid and the amine groups of the dendrimers is involved.