Low Generation Polyamidoamine Dendrimers Research Articles

Low generation polyamidoamine dendrimers (PAMAM) and biotin-PAMAM conjugate – the detailed structural studies by 1H and 13C nuclear magnetic resonance spectroscopy

Introduction. The concept of targeted drug delivery is nowadays based on nanoparticle transporters. Such drug delivery systems for cancer cells should follow the requirements like: efficient drug release, selective binding and internalization to cancer cells. The anticancer drug selectivity can be achieved by attachment of cancer cell-recognizing molecules, like biotin. Among nanosized carriers the PAMAM dendrimers are tested intensely, especially they can be modified by covalent attachment of prodrug molecules and biotin as targeting molecule. Aim. We aimed at construction and characterization of a conjugate formed between PAMAM and biotin (Biot). The nuclear magnetic resonances is powerful tool to determine both the structure and stoichiometry of the conjugate. Material and methods. PAMAM G0 has been synthesized and functionalized with biotin by reaction with N-hydroxysuccinimide ester of biotin to obtain G0 double-substituted with biotin. All the compound were thoroughly characterized by the NMR spectroscopy. Results. The conjugate of PAMAM G0 dendrimer with two amide-bonded biotin molecules was obtained and fully characterized by NMR spectroscopy. Conclusion. N-hydroxysuccinimide ester of biotin spontaneously reacts with PAMAM G0 to obtain the conjugate of 2:1 biotin: G0 stoichiometry. The latter was designed as a targeting molecule in formation of megameric multidrug delivery system.

Understanding AuNP interaction with low-generation PAMAM dendrimers: a CIELab and deconvolution study

Low-generation polyamidoamine (PAMAM) dendrimers are known to adsorb on the surface of gold nanoparticles (AuNPs) causing aggregation and color changes. In this paper, a thorough study of this affinity using absorption spectroscopy, colorimetric, and emission methods has been carried out. Results show that, for citrate-capped gold nanoparticles, interaction with the dendrimer is not only of an electrostatic character but instead occurs, at least in part, through the dendrimer’s uncharged internal amino groups. The possibilities of the CIELab chromaticity system parameters’ evolution have also been explored in order to quantify dendrimer interaction with the red-colored nanoparticles. By measuring and quantifying 17 nm citrate-capped AuNP color changes, which are strongly dependant on their aggregation state, binding free energies are obtained for the first time for these systems. Results are confirmed via an alternate fitting method which makes use of deconvolution parameters from absorbance spectra. Binding free energies obtained through the use of both means are in good agreement with each other.

Comparative study of calf-thymus DNA complexation by low generation PAMAM dendrimers and linear cationic PEGylated block copolymers by time-resolved fluorescence spectroscopy

Detailed biophysical knowledge of polyplexes formed by complexation of DNA and a cationic agent is one of the primary requirements for their successful application in vivo. In this present work, time-resolved fluorescence spectroscopy was used to understand the complexation process between i) calf-thymus DNA (ctDNA) and a series of cationic PEGylated block copolymers (BCPs), and ii) ctDNA and commercially available Polyamidoamine (PAMAM) dendrimers of low generations (G1 and G3). Studies revealed that the nature of the polyplexes formed after the DNA compaction process were quite different in the two cases mentioned above, as it depends largely on the nature and structure of the cationic polymers under study. In case of low generation PAMAM dendrimers (G1–G3), the DNA dendriplexes formed were seen to have a relatively less relaxed complex state, as compared to the polyplexes formed between PEGylated cationic BCPs with DNA. In case of cationic BCP37 with the maximum PEG content, the resultant DNA polyplex existed in the most easily relaxed state i.e., DNA was not folded into a fixed conformation but rather existed in several conformations. As the existence of the polyplexed DNA in easily relaxed state eases the release of DNA in presence of biological polyanions in the cells, this kind of a study might be useful for the designing of effective non-viral systems for DNA delivery in near future.

Synergistic stabilization of shale by a mixture of polyamidoamine dendrimers modified bentonite with various generations in water-based drilling fluid

The amine terminated polyamidoamine (PAMAM) dendrimers were investigated as potential shale stabilizers for the first time. Its inhibitive properties were characterized by a bentonite inhibition test and a shale cuttings dispersion test. The interaction between PAMAM dendrimers of various generations and sodium bentonite was examined by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). The hydration and dispersion of shale can be effectively inhibited with PAMAM dendrimers. The decrease of pH value in the dendrimer aqueous solution improved the inhibitive performance. For lower generations of dendrimer growth (G0 to G3), the inhibitive level decreased with the increase of generation. For higher generations (G4, G5), the inhibitive level increased with the increase of generation. Low generation PAMAM dendrimers could penetrate into the clay interlayer space, but exhibited highly oblate intercalation behaviors. G0 intercalated into the interlayer space with a monolayer conformation as concentration increased, while G1, G2, G3 and G4 intercalated into the interlayer space with monolayer arrangement at low concentrations, and mixed phase orientation at high concentrations. G5 could not fully intercalate into the interlayer space due to the steric hindrance. According to the interaction between PAMAM and clay, effective internal and external inhibition on shale hydration and dispersion could be obtained with the combination of low generation G0 and high generation G5. A new water-based drilling fluid including G0 as shale swelling inhibitor and G5 as shale dispersion inhibitor was established and exhibited excellent inhibitive properties.

Stealth dendrimers for drug delivery: correlation between PEGylation, cytocompatibility, and drug payload

It is advantageous to utilize low generation polyamidoamine (PAMAM) dendrimers for drug delivery because low generations (generation 4.0 or below) have more biologically favorable properties as compared to high generations. Nevertheless, modification of low generation dendrimers with PEG to create stealth dendrimers is still necessary to avoid potential side effects by long term accumulation. However, low generation dendrimers have much fewer surface sites for drug loading as compared to higher generations. To efficiently utilize low generation dendrimer-based stealth dendrimers for drug loading, PEGylation needs to be optimized. In this study, we synthesized a series of stealth dendrimers based on low generation Starburst PAMAM dendrimers (i.e., G2.5, G3.0, G3.5, and G4.0) and quantitatively assessed PEGylation efficacy in modulating cytocompatibility of low generation PAMAM dendrimers. Cytocompatibility of stealth dendrimers was examined using endothelial cells. The results showed that PEGylation degree on low generation dendrimers could be dramatically reduced to leave as many unoccupied surface groups as possible for drug loading, while maintaining the drug carrier cytocompatibility. 3PEGs-G3.0 and 10PEGs-G4.0 were considered initially optimized stealth dendrimers that would be further modified to deliver drugs of interest. Correlation of PEGylation, cytocompatibility, and drug payload allowed us to optimize low generation dendrimer-based stealth dendrimers for drug delivery and advance the understanding of structure-property relationship of stealth dendrimers.

Effect of pH on the solubility and release of furosemide from polyamidoamine (PAMAM) dendrimer complexes

The complexation of the practically insoluble drug furosemide (acidic p K a 3.22) with lower generation PAMAM dendrimers showed a significant release dependence on the ionization state of the drug. UV and FTIR studies suggested that the drug was localized in the interior of the dendrimer. The dendrimer amine, amide and ester groups, demonstrated pH-dependent ionization as did the drug carboxylic acid group and it was proven that the most efficient drug complexation was achieved in slightly acidic conditions (pH 4.0–6.0). At this pH, amide groups in the dendrimer cavities were at least partially ionized to expose a positive charge whilst the furosemide carboxylic acid ionized to great extent (pH > p K a) resulting in electrostatic complexation. Conversely, higher release rates were observed in acidic conditions (pH 1.2) where furosemide was virtually unionized, emphasizing the importance of the drug ionization state in the determination of drug release. Despite the complex interactions between the dendrimer and drug and its effects on release kinetics, the dendrimers resulted in higher solubility of the drug and contributed significantly to the array of available techniques to increase the solubility of poorly water-soluble drugs that are very abundant in industry today. Complexation with low generation PAMAM dendrimers (<generation 4) could provide opportunities to both increase drug solubility and tuning of the release profile for practically insoluble drugs.