Polyamide-amine Dendrimer Research Articles

Preparation, characterization and application of the Pb-ion-imprinted polymers based on epoxy resin and polyamide-amine dendrimers

Preparation, characterization and application of the Pb-ion-imprinted polymers based on epoxy resin and polyamide-amine dendrimers

Injectable polyamide-amine dendrimer-crosslinked meloxicam-containing poly-γ-glutamic acid hydrogel for prevention of postoperative tissue adhesion through inhibiting inflammatory responses and balancing the fibrinolytic system

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from ∼ 57.31 kPa to ∼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of ∼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.

Zwitterionic Injectable Hydrogel-Combined Chemo- and Immunotherapy Medicated by Monomolecular Micelles to Effectively Prevent the Recurrence of Tumor Post Operation.

Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on "thiol-ene" click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.

The effect of cationic polyamide-amine dendrimer on HLD equation and interface behavior of nonionic polyether water clarifier

Cationic polyamide-amine dendrimer can promote the clarification performance of nonionic block polyether water clarifier for treating produced water from heavy oil field, but the reason is lack of study. In this paper, a cationic polyamide-amine dendrimer TA which can effectively improve the oil removal speed of nonionic polyether DMEA-PE and reduce the onset temperature of DMEA-PE clarification performance was prepared, and the reason was explored from both thermodynamic and dynamic aspects by studying the effect of TA on the hydrophilic-lipophilic deviation (HLD) equation and oil-water interface behavior of DMEA-PE. The research results showed that TA moved up the HLD vs T curve of DMEA-PE and decreased its temperature corresponding HLD = 0, which was a favor of decrease in onset temperature of DMEA-PE clarification performance. TA had no effect on the DMEA-PE's capacity of oil-water interface adsorption and decreasing oil-water interface film strength. However, TA can reduce the electronegativity of oil droplet in water and enhance the oil droplets coalescence, hence the oil removal speed and efficiency of DMEA-PE were enhanced. This is the first time that HLD concept was used to investigate the action mechanism of composite water clarifier and the results are useful for the water clarifier design.

Dendrimer modified composite magnetic nano-flocculant for efficient removal of graphene oxide

Graphene oxide (GO) as an emergingnanomaterial has been widely used in water purification. However, practical removal of GO from water environment and industrial waste liquid remains a critical challenge.Here, a poly (amideamine)dendrimer (PAMAM) modified composite magnetic nano-flocculant (Fe3O4@SiO2@PAMAM) was fabricated and a new strategy for removal of GO was proposed combining the advantages of flocculation with magnetic separation. Results showed that high removal efficiency of more than 82.41 % could be attained under the conditions of an initial GO concentration of 100 mg/L, flocculation time of 60 s, Fe3O4@SiO2@PAMAM dose of 100 mg/L, and pH of 6.0. The maximum removal capacity of Fe3O4@SiO2@PAMAM for GO was approximately 238.10 mg g−1. Based on the charge neutralization and sweep flocculation, the prepared Fe3O4@SiO2@PAMAM demonstrated excellent application performance for removing GO in surface water, domestic sewage, and industrial waste liquid. A new magnetic nano-flocculant and an alternative technology strategy for treatment of GO was presented.

An Intracellular Self-Assembly-Driven Uninterrupted ROS Generator Augments 5-Aminolevulinic-Acid-Based Tumor Therapy.

Free radical therapy based on 5-aminolevulinic acid (ALA, a precursor of the photosensitizer protoporphyrin IX (PpIX)) has been approved by the US Food and Drug Administration for clinical tumor treatment. However, PpIX can be quickly converted into photoinactive heme, leading to unexpectedly paused production of free radicals and severely hindering its therapeutic benefits. Here, inspired by the natural biotransformation of ALA (ALA-PpIX-heme), an uninterrupted reactive oxygen species generator (URG) that converts useless heme to peroxidase mimics via intracellular self-assembly is developed. The URG is prepared by enwrapping ALA-loaded polyamide-amine dendrimers in red blood cell membrane vesicles with a further surface modification of G-quadruplex-structured AS1411. The URGs realize "1 O2 -•OH" uninterrupted generation through "recycling waste" in two steps: i) PpIX generates 1 O2 under laser irradiation; and ii) the photoinactive metabolite heme self-assembled with AS1411 to catalyze H2 O2 conversion into •OH. Interestingly, the specific generation of 1 O2 in mitochondria and •OH in nuclei further augments the free-radical-induced damage. It is demonstrated that URG can continuously produce free radicals for 6 h postirradiation, and shows 3.3-times more than that of the nonassembly group, achieving nearly 80% regression of tumors in vivo.

Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe.

The conventional targeted delivery of chemotherapeutic and diagnostic agents utilizing nanocarriers is a promising approach for cancer theranostics. Unfortunately, this approach often faces hindered tumor access that decreases the therapeutic index and limits the further clinical translation of a developing drug. Here, we demonstrated a strategy of simultaneously double-targeting the drug to two distinct cites of tumor tissue: the tumor endothelium and cell surface receptors. We used fourth-generation polyamideamine dendrimers modified with a chelated Gd and functionalized with selectin ligand and alpha-fetoprotein receptor-binding peptide. According to the proposed strategy, IELLQAR peptide promotes the conjugate recruitment to the tumor inflammatory microenvironment and enhances extravasation through the interaction of nanodevice with P- and E-selectins expressed by endothelial cells. The second target moiety—alpha-fetoprotein receptor-binding peptide—enhances drug internalization into cancer cells and the intratumoral retention of the conjugate. The final conjugate contained 18 chelated Gd ions per dendrimer, characterized with a 32 nm size and a negative surface charge of around 18 mV. In vitro contrasting properties were comparable with commercially available Gd-chelate: r1 relaxivity was 3.39 for Magnevist and 3.11 for conjugate; r2 relaxivity was 5.12 for Magnevist and 4.81 for conjugate. By utilizing this dual targeting strategy, we demonstrated the increment of intratumoral accumulation, and a remarkable enhancement of antitumor effect, resulting in high-level synergy compared to monotargeted conjugates. In summary, the proposed strategy utilizing tumor tissue double-targeting may contribute to an enhancement in drug and diagnostic accumulation in aggressive tumors.

Phosphate Derivative Recognition Using Polyamide Amine Dendrimer Reagent Modified by Dipicorylamine Ligand

Phosphate Derivative Recognition Using Polyamide Amine Dendrimer Reagent Modified by Dipicorylamine Ligand

A Review: Adsorption and Removal of Heavy Metals Based on Polyamide-amines Composites.

In recent years, the problem of heavy metal pollution has become increasingly prominent, so it is urgent to develop new heavy metal adsorption materials. Compared with many adsorbents, the polyamide-amine dendrimers (PAMAMs) have attracted extensive attention of researchers due to its advantages of macro-molecular cavity, abundant surface functional groups, non-toxicity, high efficiency and easy modification. But in fact, it is not very suitable as an adsorbent because of its solubility and difficulty in separation, which also limits its application in environmental remediation. Therefore, in order to make up for the shortcomings of this material to a certain extent, the synthesis and development of polymer composite materials based on PAMAMs are increasingly prominent in the direction of solving heavy metal pollution. In this paper, the application of composites based on PAMAMs and inorganic or organic components in the adsorption of heavy metal ions is reviewed. Finally, the prospects and challenges of PAMAMs composites for removal of heavy metal ions in water environment are discussed.

Compatibilization and Toughening of Biodegradable Polylactic Acid/Cellulose Acetate Films by Polyamide Amine Dendrimers

Due to the poor compatibility caused by the large difference in hydrophilicity and interface between polylactic acid (PLA) and cellulose acetate (CA), the blending of the two materials is difficult and the application is limited. To solve this problem, a type of polyamide amine (PAMAM) dendrimer was introduced to modify PLA/CA blends in this work. The results showed that PAMAM could improve the compatibility of PLA/CA blends, promote the distribution of CA and crystallization of PLA. At the same time, adding PAMAM could enhance the mechanical properties of the blend material, and the toughness and tear strength were increased by 551% and 141%, respectively. In addition, the incorporation of PAMAM increased hydrophobicity and oxygen permeability of PLA/CA blends, and the oxygen permeability could be increased by up to three orders of magnitude. Degradation test results showed that the blend exhibited good biodegradability. The overall performance of the PLA/CA blend film was optimal when the content of PAMAM was 3 phr. The biodegradable blend films with excellent performance provided wide application prospect in the food green packaging fields.

Polyamide Amine Dendrimer Nanoparticles Conjugated with Cis-Diamminedichloroplatinum (CDDP) and miRNA-200c Inhibitor Suppresses Lung Cancer Cell Proliferation

Our study elucidates the effect of folate polyamide amine dendrimer nanoparticles targeting delivery of miRNA-200c inhibitor and CDDP on lung cancer cells proliferation. We established polyamide amine dendrimer nanoparticles binding with CDDP and miRNA-200c inhibitor (Den-PEI-CDDP-siRNA-FA), TEM was employed to detect the morphology of nanoparticles. Agarose gel assay was selected for stabilization test. Cell proliferation were detected by trypanosoma blue exclusion method. The expression of miRNA-200c targeted APKPA12 and apoptosis-related proteins were detected by Western blot and PCR. Finally, apoptosis was analyzed by flow cytometry. Den-PEI-CDDP-siRNA-FA nanoparticles showed excellent stability and drug encapsulation ability. Nanoparticles targeting for FRA to co-deliver siRNA and CDDP could significantly promote cell apoptosis, increase apoptosis-related protein expression, and inhibit cell proliferation. Besides, nanoparticles exerted less venomous effect than untargeted nanoparticles in MRC9 lung fibroblast. Den nanoparticle targeting FRA might be used as the carrier for joint applications with siRNA and CDDP for treating lung cancer.

Gold Nanoparticle-Optimized Computed Tomography Imaging Combined with Transcranial Magnetic Stimulation on Rehabilitation Training of Children with Cerebral Palsy

Traditional computed tomography (CT) contrast agents, such as iodine-containing small molecules (omnipaque), have limitations in some applications. The development of nanotechnology has made it possible to develop CT contrast agents based on this technology. In this study, a large number of surface functional groups of the fifth-generation polyamide-amine dendrimer (P5-NH2) were applied to functionally modify polyethylene glycol (PEG), targeting molecules, or drugs, which were used as the carrier of CT contrast agents. With the help of sodium borohydride (NaBH4), there was a rapid reduction. The fluorescein thiocyanate (FT) and PEG modified with lactobionic acid (PEG-LA) weres connected before gold coating to obtain gold nanoparticles coated with targeted dendrimer (Au(P5-LA)DENPs). In the experiment, the gold nanoparticles were characterized, and the liver cancer nude mouse model was established, so as to analyze the CT imaging performance of the material. Besides, the above was applied in the motor function of children with cerebral palsy, and the improvement effect of CT imaging combined with transcranial magnetic stimulation based on the preparation of nanomaterials on the movement function of children was analyzed and demonstrated with the help of graph theory. The results showed that the average particle size of gold nanoparticles was 1.88 nm. Within the range of 5 °C–50 °C and pH = 4–7, the physical properties of the aqueous solution of this material were stable. What’s more, the cell activity still exceeded 80% when the material concentration reached 2000 nm. The nude mouse model of liver cancer indicated that the CT imaging based on this material enhanced the image contrast effect of the tumor part, and the material had no obvious toxic and side effects. CT imaging based on the preparation of nanomaterials can promote transcranial magnetic stimulation to accelerate the efficiency of brain movement, accelerate the global and local information exchange and integration speed of brain network, thereby improving the movement function of children.

Preparation of Gd-Au Dendrimer-Entrapped Gold Nanoparticles-Folic Acid Nanoparticles and Its Application in Computed Tomography/Magnetic Resonance Imaging Dual-Modality Diagnosis of Abdominal Tumors

ABSTRACTThe development of nanomaterials, especially the development of multi-modality imaging nanoprobe technology has become a reality for tumor imaging diagnosis. In this study, the gadolinium ion chelating agent (2,2′,2′′-(10-(2-(2, 5-dioxopyrrolidin-1-oxyl)-2 oxoethyl)-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7-tri)triacetic acid) (DOTA-NHS) and polyethylene glycol (PEG)-modified targeting ligand PEG-folic acid (FA) were grafted onto the PEG-modified fifth-generation polyamide-amine dendrimer (P5-NH2), which were undertaken as standards to wrap gold nanoparticles. Then, remaining amino group was acetylated to acquire Gd–Au DENPS-FA nanoparticles. Biocompatibility and cytotoxicity of nanoparticles were analyzed while characterizing them. The cases with unidentified tumors (mass diameter >4.5 cm) of abdominal or pelvic origin were selected and used for clinical study of computed tomography (CT)/magnetic resonance imaging (MRI) dual-modality abdominal tumors. In the test, average particle size of Gd-Au DENPs-FA nanoparticles was 4.2 nm, and they had good water solubility and stability in aqueous solution. When concentration of Au+ nanoparticles increased, the cell morphology remained normal, only a small number of round cells appeared, and the cell activity remained above 80%. GD-Au DENPs-FA nanoparticles had a good targeting specificity for KB cells with high folate receptor expression. During 6–24 hours of injection, the signal at the tumor site of the patient was enhanced markedly, namely the targeted gold nanoparticles were bound to the tumor tissue and the metabolic rate was slow. Based on this material, CT/MRI imaging could be performed in the patient’s body and further used for the early diagnosis of abdominal tumors.

Remineralization of dentin induced by a compound of polyamide-amine and chlorhexidine in a resin dentin bonding microenvironment.

BackgroundThe purpose of this study was to investigate the effect of a complex of polyamide-amine dendrimer (PAMAM) and chlorhexidine gluconate (CG) on remineralization of dentin in an artificial simulated resin dentin bonding microenvironment.MethodsThe structure of this complex was characterized by FT-IR. Twelve standard dentin samples were randomly divided into four treatment fluid groups namely a PAMAM group, CG group, PAMAM + CG group, and deionized water group. A microenvironmental mineralization model was established in vitro with 50 µm gap width between resin and dentin. The dentin surface was observed by a scanning electron microscope (SEM), and the chemical structure of the surface was analyzed by X-ray energy spectrum (EDS), X-ray diffraction (XRD), and laser Raman spectroscopy.ResultsSEM showed the density of dentinal tubules exposed in the PAMAM group decreased after a 14-day immersion, with corn rod-shaped crystal structures gathered around the tubules. In addition, visible mineralization occurred in partial areas of the CG group, rod-shaped crystals and in comparison, dentinal tubules in the PAMAM + CG group were almost completely covered by flaky crystal structures. Raman spectrum analysis showed that crystals formed by PAMAM, CG, and PAMAM + CG solution all had strong phosphate characteristic peaks, indicating the presence of hydroxyapatite (HA), that of the PAMAM + CG group was the strongest. The EDS results showed that the Ca and P levels of the PAMAM group and the CG group were slightly higher than those of the deionized water group, while PAMAM + CG group significantly higher than the others, Ca/P value approaching 1.67. The results of XRD showed the characteristic peaks of hydroxyapatite detected by the PAMAM + CG group at 2θ=26.0 (002), 2θ=32.0 (211), and 2θ=33.0 (112) were high and sharp, with a few diffraction line burrs indicating it had high crystallinity and purity. The Scherrer equation results showed that the appearance and size of the grains formed by the PAMAM + CG group were basically consistent with those of healthy dentin.ConclusionsAltogether, the compound of polyamide-amine dendrimer and chlorhexidine could induce the remineralization of human dentin in a resin dentin bonding microenvironment with a gap of 50 µm to form a crystal structure similar to dentin hydroxyapatite.

Research progress on the biomimetic remineralization of hard tooth tissues based on polyamide-amine dendrimer

Polyamide-amine (PAMAM) dendrimer, a new hyperbranched macromolecular polymer, is considered an "artificial protein" by many scholars on account of its excellent chemical and biological characteristics. PAMAM has internal cavities and a large number of reactive terminal groups. These structures allow the polymer to be used as a bionic macromoleculethat could simulate the biomimetic mineralization of the natural organic matrix on the surface of tooth tissue. Specifically, PAMAM can beused as an organic template to regulate mineral nucleation and crystal growth; thus, the polymerisa more ideal dental restoration material than traditional allogenic materials. This article reviews research progress on thePAMAM-induced biomimetic mineralization of hard tooth tissues.

Preparation and in vitro evaluation of arsenic trioxide glioma targeting drug delivery system loaded by PAMAM dendrimers co-modified with RGDyC and PEG

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. in vitro 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 in vitro. Accordingly, the drug delivery system has a better anti-tumour effect across the blood brain barrier (BBB) in vitro, which further proves the tumour targeting of RGDyC.

Synthesis of a novel structure for the oral delivery of insulin and the study of its effect on diabetic rats

Common materials used for drug delivery in the body are: liposomes, micelles, polymer capsules, dendrimers, nanoparticles, porous materials, etc. Drug delivery system should be inert, biodegradable, have high biocompatibility and the ability to load large amounts of the drug with known concentration while having a simple and economical sterilizing process. In this study we produced mesoporous silica nanostructures coated with polyamide amine dendrimer that were placed in chitosan-gelatin scaffolds. At every step of the synthesis, the products were identified using different methods, including XRD, FT-IR, SEM, and TGA. The final drug was studied in terms of in vitro & in vivo and MTT toxicity was evaluated.

Formulation of temozolomide-loaded nanoparticles and their targeting potential to melanoma cells.

The present study was carried out to prepare and evaluate a temozolomide (TMZ)-loaded polyamide-amine dendrimer (PAMAM)‑based nanodrug delivery system, and to explore its ability to target human melanoma (A375) cells invitro. Firstly, PAMAM-PEG and PAMAM-PEG-GE11 were synthesized by substitution and addition reactions, and their products were identified and characterized by fourier transform-infrared (FTIR), proton nuclear magnetic resonance (1H-NMR) and transmission electron microscopy (TEM), as well as differential light scattering (DLS). Using fluorescein isothiocyanate (FITC)-modified PAMAM, we synthesized FITC-PAMAM, FITC-PAMAM-PEG and FITC-PAMAM-PEG-GE11. Fluorescence microscopy and flow cytometry were used to monitor the uptake of A375 cells of these three nanomaterials. Secondly, TMZ-PAMAM‑PEG‑GE11-HA drug complexes were prepared by ultrasonic emulsification, and their particle size, zeta potential and morphology were evaluated by DLS and TEM. Drug loading (DL) and encapsulation efficiency (EE) were assayed by ultraviolet spectrophotometry. Thirdly, we ascertained whether TMZ-PAMAM-PEG-GE11-HA conjugates could target A375 cells invitro. The TMZ-PAMAM‑PEG‑GE11-HA nanodrug delivery system was successfully synthesized according to FTIR and 1H-NMR. Its mean particle size was 183.2nm and zeta potential was -0.01mV. It was a regular sphere with good uniformity. The EE of TMZ-PAMAM-PEG-GE11-HA was ~50.63% and DL ~10.4%. TMZ-PAMAM-PEG-GE11-HA targeted A375 cells invitro. In conclusion, the TMZ-PAMAM‑PEG-GE11-HA nanodrug delivery system was successfully prepared, and demonstrated its potential for targeting A375 cells invitro. This system enhanced the sensitivity of A375 cells to TMZ, and provided a novel targeted strategy for the treatment of metastatic melanoma.

Thermodynamic Interaction between PAMAM G4-NH2, G4-OH, G3.5-COONa Dendrimers and Gemcitabine in Water Sotutions

The thermodynamics of complex formation of polyamideamine dendrimers: cationic PAMAM G4-NH2, neutral PAMAM G4-OH and anionic PAMAM G3.5-COONa with gemcitabine hydrochloride, an antitumor drug, in water at a temperature of 250C was studied. The investigations were carried out with the use of ITC measurements allowing one to determine the number of the drug molecules bonded by the dendrimer macromolecule, the equilibrium constants of the complex formed and the values of enthalpy and entropy of their formation. The measurements results obtained show different numbers of the drug molecules bonded by dendrimer macromolecules depending on the properties of their terminal groups.

Synthesis of porphyrins as precursors to PAMAM dendrimers and their metal chelating properties

Novel meso-porphyrins were synthesized via microwave assistance and implemented as centers to polyamide amine (PAMAM) dendrimers. The molecular structures of the porphyrins were characterized by UV-Vis, 1 H and 13 C NMR spectroscopy. In addition, porphyrin-PAMAM dendrimers were characterized by 1 H and 13 C NMR spectroscopy. The molecular weight of the prepared dendrimers were confirmed by MALDI-TOF mass spectrometry. These porphyrin-core-PAMAM-modified dendrimers were used as templates to form Ag 0 species and doped nylon membranes, using the XPS technique to confirm the chemical reduction of the metal cation.