Polyamidoamine Dendrimers Research Articles

Anti-Tissue-Transglutaminase IgA Antibodies Presence Determination Using Electrochemical Square Wave Voltammetry and Modified Electrodes Based on Polypyrrole and Quantum Dots

A novel electrochemical detection method utilizing a cost-effective hybrid-modified electrode has been established. A glassy carbon (GC) modified electrode was tested for its ability to measure electrochemical tTG antibody levels, which are essential for diagnosing and monitoring Celiac disease (CD). Tissue transglutaminase protein biomolecules are immobilized on a quantum dots-polypyrrole nanocomposite in the improved electrode. Initial, quantum dots (QDs) were obtained from Bombyx mori silk fibroin and embedded in polypyrrole film. Using carbodiimide coupling, a polyamidoamine (PAMAM) dendrimer was linked with GQDs-polypyrrole film to improve sensor sensitivity. The tissue transglutaminase (tTG) antigen was cross-linked onto PAMAM using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC)-N-hydroxy succinimide (NHS) chemistry to develop a nanoprobe that can detect human serum anti-tTG antibodies. The physicochemical characteristics of the synthesized nanocomposite were examined by FTIR, UV-visible, FE-SEM, EDX, and electrochemical studies. The novel electrode measures anti-tissue antibody levels in real time using human blood serum samples. The modified electrode has great repeatability and an 8.7 U/mL detection limit. Serum samples from healthy people and CD patients were compared to standard ELISA kit assays. SPSS and Excel were used for statistical analysis. The improved electrode and detection system can identify anti-tissue antibodies up to 80 U/mL.

The Role of Light Irradiation and Dendrimer Generation in Directing Electrostatic Self-Assembly

pH-responsive polyamidoamine (PAMAM) dendrimers are used as well-defined building blocks to design light-switchable nano-assemblies in solution. The complex interplay between the photoresponsive di-anionic azo dye Acid Yellow 38 (AY38) and the cationic PAMAM dendrimers of different generations is presented in this study. Electrostatic self-assembly involving secondary dipole–dipole interactions provides well-defined assemblies within a broad size range (10 nm–1 μm) with various shapes. The size and shape of these assemblies were determined using dynamic and static light scattering (DLS/SLS) and small-angle neutron scattering (SANS); ζ-potential measurements were performed to elucidate the charge characteristics, revealing the effective surface charge density of the nano-objects as an important parameter in the size and shape control. UV–vis spectroscopy and isothermal titration calorimetry (ITC) were employed to investigate the interaction on a molecular level and from a thermodynamic point of view. The results show that the amount of isomerized cis dye depends on the dendrimer generation because of a photoprotective effect through electrostatics for lower generations and through dipole–dipole interactions for higher generations; as the cis dye and trans dye bind with different strength, the amount of cis dye then again encodes the charge density and thereby the particle size and shape.

Hydration and Biodistribution of Zwitterionic Dendrimers Conjugating a Sulfobetaine Monomer and Polymers.

Zwitterionic polymers exhibit strong hydration, high biocompatibility, and antifouling properties. Dendrimers are regularly branched polymers, which are used in the drug delivery system (DDS). In this study, we synthesized zwitterionic monomer- and polymer-conjugated dendrimers as a biocompatible nanoparticle to investigate the relation between the hydration property and biodistribution. A sulfobetaine monomer (SBM) was conjugated at the termini of the polyamidoamine (PAMAM) dendrimer. Polysulfobetaines (PSBs) were produced by reversible addition-fragmentation chain transfer polymerization and were also conjugated at the termini. Intermediate water, that is, water molecules loosely bound to the material, can be estimated from the melting peaks at less than 0 °C in differential scanning calorimetry (DSC) measurement. Our DSC results showed that the PSB-conjugated dendrimers (PSM-dens) contained more intermediate water than the SBM-conjugated dendrimer (SBM-den). PSB-dens accumulated in the tumor after intravenous administration, but SBM-den did not. These suggested that the amount of intermediate water, that is, the hydration property, was related to the biodistribution of the zwitterionic dendrimers. This relation is a possible design criterion for drug carriers. PSB-dens accumulated in the tumor even after the second injection, possibly overcoming the accelerated blood clearance observed with poly(ethylene glycol)-modified nanoparticles. Thus, this kind of zwitterionic polymer-conjugated dendrimer is useful for the DDS in cancer treatment.

Probing Macromolecular Conformation in Restricted Geometry by PEF: Application to Hydrophobically Modified PAMAM Dendrimers Isolated Inside Surfactant Micelles.

The conformation of a series of zero-generation polyamidoamine dendrimers end-labeled with four 1-pyrene-butyroyl, -hexanoyl, -octanoyl, -decanoyl, and -dodecanoyl derivatives, referred to as the PyCX-PAMAM-G0 samples with X = 4, 6, 8, 10, and 12, respectively, was characterized in N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and aqueous solutions of 50 mM sodium dodecyl sulfate (SDS) or 50 mM dodecyltrimethylammonium bromide (DTAB). The conformation of the PyCX-PAMAM-G0 samples was determined from the global model-free analysis (MFA) of the fluorescence decays, which yielded the average rate constant (⟨k⟩) for pyrene excimer formation (PEF) between an excited and a ground-state pyrenyl labels, with ⟨k⟩ being proportional to the local concentration ([Py]loc) of the pyrenyl labels within the macromolecular volume; ⟨k⟩-vs-[Py]loc plots yielded straight lines passing through the origin in DMF and DMSO, demonstrating that the internal segments of the dendrimers obeyed Gaussian statistics in these two solvents. In aqueous surfactant solutions, the hydrophobic pyrenyl labels induced the interactions of the PyCX-PAMAM-G0 dendrimers with the SDS and DTAB micelles. Plots of ⟨k⟩ as a function of [Py]loc yielded straight lines passing through the origin for the PyCX-PAMAM-G0 samples with X equal to 4, 6, and 8, indicating that the internal segments of these three dendrimers obeyed Gaussian statistics within the surfactant micelles. However, ⟨k⟩ departed from the straight lines for the PyCX-PAMAM-G0 samples with X = 10 and 12 associated with the SDS and DTAB micelles. This behavior indicated that [Py]loc was much larger than expected for the dendrimers prepared with longer alkanoyl linkers. This behavior was attributed to strong hydrophobic interactions between the longer linkers and the dodecyl tails of the surfactants in the hydrophobic core of the micelles, which induced a conformational change for the dendrimers inside the micelles, that could be probed at the molecular level by PEF.

TEMPERATURE INDICES OF WELL KNOWN DENDRIMER NETWORKS

Chemical graph theory is a branch of graph theory. In this field, molecules are modeled using graph theory and a mathematical approach is obtained. Thus, predictions can be made about the physical, chemical and bioactivity properties of molecules. In this study, temperature indices depending on the vertex degree are considered. Temperature indices of Polyamidoamine (PAMAM) dendrimers, Porphyrin core dendrimers are obtained and the results are compared numerically using the MATLAB program.

Surface-modified dendrimer nanoconjugate for targeting delivery of rifampicin

ObjectiveThe study aimed to formulate and evaluate the efficiency of surface-modified Polyamidoamine dendrimer (PAMAM) as a targeted nanocarrier for the antimycobacterial agent rifampicin. MethodsThe periphery of dendrimer was modified with mannose using α-D-mannopyranosylphenyl isothiocyanate and characterized using analytical techniques i.e., infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Then, rifampicin was encapsulated into mannosylated dendrimers and evaluated for size, shape, encapsulation efficiency (EE%), drug-dendrimer interaction, and drug release. The toxicity of the nanoconjugates were assessed towards macrophages using the MTT technique. The study investigated the internalization of dendrimer nanoparticles into macrophages to assess the impact of mannose conjugation. Dendrimers were fluorescently labelled and the internalization was quantified using a fluorescence spectroscopy and flow cytometer methods. ResultsMannosylated dendrimers with different mannose densities were successfully developed. The nanoparticles were within the nanoscopic scale. The dendrimers appeared spheroidal under scanning electron microscopy (SEM), and thermal analysis confirmed the conjugation of rifampicin into the dendrimers. The nanoparticles exhibited a good EE% for rifampicin at 10.34 % w/w. After surface mannosylation, the EE% further increased, ranging from 43.43 % to 57.91 % w/w. Mannose-functionalized dendrimers prolonged rifampicin release in physiological pH, while a rapid release in pH 4.5 medium was noticed. The cytotoxicity of the dendrimers in RAW macrophages was considerably reduced after mannose functionalization. In vitro studies indicated that mannose significantly increased the macrophage uptake of nanoconjugates, likely via lectin receptor-mediated endocytosis. ConclusionOverall results suggested mannosylated dendrimers as an effective targeted pulmonary delivery system for rifampicin with negligible cytotoxicity.

Cholesterol‐Conjugated PAMAM Dendrimers: Enhancing Stability, Drug Delivery Efficiency, and In Vitro Anticancer Performance

ABSTRACTNanomaterials offer great potential in cancer treatment, particularly in drug delivery, where their unique properties allow for targeted therapy, increasing treatment efficacy while minimizing side effects. Dendrimers, with their highly branched structure, are ideal candidates for drug delivery. However, polyamidoamine (PAMAM) dendrimers, despite their versatility, exhibit cytotoxicity. Modifying PAMAM dendrimers with cholesterol through p‐nitrophenyl chloroformate (NPC) mediation enhances their biocompatibility and targeting ability, especially toward cancer cells. In this study, PAMAM G3.0 was successfully synthesized and conjugated with cholesterol to form G3C nanogels, with a nanoscale size of 83.8 ± 21.9 nm. The study of cholesterol conjugation revealed that at 25% surface functionalization of G3.0, G3C exhibited stable behavior in PBS buffer for up to 8 days. The system's capacity to load single or dual drugs was also explored, demonstrating controlled drug release for over 96 h. Moreover, cholesterol modification on G3.0 significantly enhanced cell compatibility. The G3C@QU/PTX system exhibited improved targeting toward HeLa cancer cells in vitro compared to healthy fibroblast cells. This research provides a strong foundation for developing nanomaterials for targeted cancer treatment.

Future-Oriented Nanosystems Composed of Polyamidoamine Dendrimer and Biodegradable Polymers as an Anticancer Drug Carrier for Potential Targeted Treatment.

Background/Objectives: Camptothecin (CPT) is a well-known chemical compound recognized for its significant anticancer properties. However, its clinical application remains limited due to challenges related to CPT's high hydrophobicity and the instability of its active form. To address these difficulties, our research focused on the development of four novel nanoparticulate systems intended for either oral or intravenous administration. Methods: These nanosystems were based on a poly(amidoamine) (PAMAM) dendrimer/CPT complex, which had been coated with biodegradable homo- and copolymers, designed with appropriate physicochemical properties and chain microstructures. Results: The resulting nanomaterials, with diameters ranging from 110 to 406 nm and dispersity values between 0.10 and 0.67, exhibited a positive surface charge and were synthesized using biodegradable poly(L-lactide) (PLLA), poly(L-lactide-co-ε-caprolactone) (PLACL), and poly(glycolide-co-ε-caprolactone) (PGACL). Biological assessments, including cell viability and hemolysis tests, indicated that all polymers demonstrated less than 5% hemolysis, confirming their hemocompatibility for potential intravenous use. Furthermore, fibroblasts exposed to these matrices showed concentration-dependent viability. The entrapment efficiency (EE) of CPT reached up to 27%, with drug loading (DL) values as high as 17%. The in vitro drug release studies lasted over 400 h with the use of phosphate buffer solutions at two different pH levels, demonstrating that time-dependent processes allowed for a gradual and controlled release of CPT from the developed nanosystems. The release kinetics of the active compound at pH 7.4 ± 0.05 and 6.5 ± 0.05 followed near-first-order or first-order models, with diffusion and Fickian/non-Fickian transport mechanisms. Importantly, the nanoparticulate systems enabled the stabilization of the pharmacologically active form of CPT, while providing protection against hydrolysis, even in physiological environments. Conclusions: In our opinion, these results underscore the promising future of biodegradable nanosystems as effective drug delivery systems (DDSs) for targeted cancer treatment, offering stability and efficacy over short, medium, and long-term applications.

Fluorinated dendrimer-mediated miR-30a delivery regulates the inflammation of macrophages and mitigates the symptoms of rheumatoid arthritis

Abnormal expression of microRNAs (miRNAs) plays a significant role in the pathogenesis of rheumatoid arthritis (RA), and thus miRNA-based therapy has emerged as a promising approach for the RA treatment. Herein, miR-30a was successfully screened and identified to be an essential mediator for the inflammation of RA. MiR-30a could directly target the Snai1 gene and further regulate the Cad11 expression to inhibit the NF-κB and MAPK signaling pathways, contributing to the anti-inflammatory effect. To enhance the therapeutic outcome of miR-30a, fluorinated polyamidoamine dendrimer (FP) was developed as the carrier to achieve the miR-30a delivery in the mice of collagen-induced arthritis. The carrier FP and miR-30a formed stable nanocomplexes and effectively mediated the transfection of miR-30a to execute the anti-inflammatory response in lipopolysaccharide-stimulated macrophages. Further, the intravenous administration of FP/miR-30a showed obvious accumulation in the inflamed joints and inhibited the inflammatory response via the Snai1/Cad11 axis, thereby contributing to the anti-arthritic efficacy. In addition, the FP/miR-30a nanocomplexes displayed favorable biocompatibility, as they did not cause the damage of organs following the systemic administration. Taken together, our study demonstrated that miR-30a is an effective anti-inflammatory oligonucleotide and the fluorinated dendrimer-mediated miR-30a delivery possesses the potential to be a promising approach for the treatment of RA and other autoimmune diseases.

Aptamer sgc8-Modified PAMAM Nanoparticles for Targeted siRNA Delivery to Inhibit BCL11B in T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disease with limited targeted therapy options. Overexpression of B-cell lymphoma/leukemia 11B is frequently observed in T-ALL and contributes to leukemogenesis. Knockdown of BCL11B inhibits T-ALL cell proliferation and induces apoptosis, making it a potential therapeutic target. However, the clinical application of siRNA therapies is hindered by challenges such as poor delivery efficiency and limited clinical outcomes. We developed a targeted delivery system for BCL11B siRNA (siBCL11B) using generation 5 polyamidoamine (G5-PAMAM) dendrimers conjugated with the sgc8 aptamer, which specifically binds to the T-ALL cell membrane protein PTK7. This nanoparticle, designated G5-sgc8-siBCL11B, was designed to selectively deliver siRNA to T-ALL cells. In vitro and in vivo experiments were conducted to evaluate its therapeutic efficacy and safety. We demonstrate that sgc8-conjugated siBCL11B nanoparticles selectively and efficiently target BCL11B-overexpressing T-ALL cells, significantly inhibiting cell viability and promoting apoptosis while exhibiting minimal impact on the viability of normal T cells. In T-ALL mouse model studies, G5-sgc8-siBCL11B and G5-siBCL11B significantly inhibited the progression of T-ALL in vivo, extending the survival of mice compared to the control (CTR), G5, and G5-sgc8 groups. Although there was no significant difference in survival between the G5-sgc8-siBCL11B and G5-siBCL11B groups, a trend towards improved survival was observed (p = 0.0993). The G5-sgc8-siBCL11B nanoparticle system demonstrated efficient delivery and significant therapeutic efficacy, highlighting its potential as a promising novel approach for the treatment of T-ALL.

PAMAM dendrimers based co-delivery of methotrexate and berberine for targeting of Hela cancer cells

Polyamidoamine dendrimer (PAMAM) is a class of synthetic macromolecular polymers for targeted drug delivery. PAMAM dendrimers are characterized by a pure defined structure, adjustable nanoscale dimensions, mono-dispersity, and versatile surface modification. The objective of this study was to study the covalent coupling of methotrexate (MTX) to PAMAM dendrimer, which was loaded with the natural product anticancer agent, berberine (BER) for the targeting of HeLa cells. The successful preparation of MTX-conjugated PAMAM loaded with BER (MTX-PAMAM-BER) was confirmed by Fourier transform infrared spectroscopy and particle size was evaluated using dynamic light scattering. The biological assays, MTT, flow cytometry, ROS levels evaluation and DAPI staining were used to assess the cytotoxicity effect of the prepared nanosystem. The findings indicated that MTX-PAMAM-BER exhibited greater suppression of tumor cell growth in comparison to BER, MTX, PAMAM-BER, and MTX-PAMAM. Besides, the noteworthy ROS level has been seen in the treated cells with MTX-PAMAM-BER. Finally, it should be stated that the fabricated MTX-PAMAM-BER co-delivery nanosystem could be a promising agent for cancer therapy and targeting.

Mechanisms and efficiency of CO2 absorption in polyamidoamine dendrimers: Experiments and theoretical calculations

To investigate the effect of amino number and viscosity on the absorption properties of PAMAM dendrimers and CO2, different initiation cores and different generations of PAMAM dendrimers were used to absorb the CO2. Molecular simulations were also employed to explain the regulatory mechanisms governing CO2 absorption, and an evaluation method of the absorption capacity was constructed for PAMAM dendrimers. The results exhibited that the viscosity of PAMAM dendritic polymers increased according to the increase of the initiator carbon chain length and nitrogen-containing functional groups. The high viscosity of G1.0 PAMAM-T and G2.0 PAMAM-D resulted in absorption loadings that were only slightly higher than those of G1.0 PAMAM-D and much lower than the theoretical capacity. The molecular simulations confirm that increasing the number of amino groups enhances the ability of PAMAM dendrimers to bind CO2, the correlation is not entirely linear. The increase in viscosity increases the resistance to mass transfer of CO2 molecules in the absorption system, thus limiting diffusion and reducing absorption efficiency. Consequently, the optimal benefits of PAMAM dendrimers are achieved only by balancing the advantages of multi-amino groups with the disadvantages of increased viscosity. 13C NMR confirms that the CO2 absorption mechanism of the PAMAM dendrimers follows the zwitterionic mechanism in which primary and secondary amines react with CO2 to produce carbamate.

Phosphorous Acid‐Functionalized Polyamidoamine Dendrimer: Efficient Scale and Corrosion Inhibition

AbstractPhosphorous‐based polymeric scale and corrosion are widely used for industrial water treatment. In this paper, phosphorous acid modified polyamidoamine dendrimer (PDD) was prepared for scale inhibition and corrosion inhibition and compared with the existing inhibitors, 2‐phosphonobutane‐1,2,4‐tricarboxylic acid (PBTCA) and polyacrylic. The scale inhibition efficiency of CaCO3 was evaluated using the static scale inhibition and conductivity method. Compared to polyacrylic acid, the dendritic structure can effectively improve the calcium carbonate scale inhibition performance of the scale inhibitor. When the concentration of PDD is 40 mg/L, the scale inhibition rate is 96%, which is higher than the scale inhibition rate of 91% for PBTCA. The conductivity experimental results reveal that PDD endows the solution with higher supersaturation degree than that of PBTCA at the same concentration. Furthermore, the nucleation induction period of PDD is 1300 s, which is more than twice that of PBTCA at a concentration below 20 mg/L. The XPS, XRD, and SEM results exhibited that PDD can adsorb on the surface of calcium carbonate crystals, changing the crystals from stable calcite to metastable aragonite and vaterite. In addition, electrochemical measurements show a corrosion inhibition rate of 82.67% at a PDD concentration of 100 mg/L. This article provides data support for the application of phosphorous acid functionalization PAMAM in scale and corrosion inhibition.

Specific isolation and quantification of PD-L1 positive tumor derived exosomes for accurate breast cancer discrimination via aptamer-functionalized magnetic composites and SERS immunoassay

PD-L1 positive tumor derived exosomes (TEXsPD−L1) play a significant role in disease progression, tumor metastasis and cancer immunotherapy. However, the overlap of PD-L1 between TEXs and non-tumor derived exosomes (non-TEXs) restricts the specific isolation and quantification of TEXPD−L1 from clinical samples. Herein, a new aptamer-functionalized and hydrophilic immunomagnetic substrate was designed by decorating generation 5 polyamidoamine dendrimers (G5 PAMAM), zwitterionic trimethylamine N-oxide (TMAO) and EpCAM (Epithelial cell adhesion molecule) aptamers on magnetic cores sequentially (Fe3O4@PAMAM@TMAO@Aptamer, named as FPTA) for rapid target and efficient capture of TEXs. The FPTA substrate gathered excellent characters of strong magnetic responsiveness of Fe3O4, abundant affinity sites of PAMAM, strong hydrophilicity of TMAO and enhanced affinity properties of EpCAM aptamers. Because of these advantages, FPTA can isolate TEXs quickly within 30min with high capture efficiency of 90.5 % ± 3.0 % and low nonspecific absorption of 8.2 % ± 2.0 % for non-TEXs. Furthermore, PD-L1 (Programmed cell death-ligand 1) positive TEXs (TEXsPD−L1) from the captured TEXs were recognized and quantitatively analyzed by utilizing SERS (surface-enhanced Raman spectroscopy) reporter molecules 4-NTP (4-Nitrothiophenol) on PD-L1 aptamers-functionalized gold immunoaffinity probe. The signal of TEXsPD−L1 was converted to SERS signal of 4-NTP at 1344 cm−1 which exhibited a linear correlation to concentration of TEXsPD−L1(R2 = 0.9905). With these merits, this strategy was further applied to clinical plasma samples from breast cancer (BC) patients and healthy controls (HC), exhibited an excellent diagnosis accuracy with area under curve (AUC) of receiver operating characteristic (ROC) curve reaching 0.988. All these results demonstrate that the FPTA immunomagnetic substrate combined with SERS immunoaffinity probe may become a generic tool for specific isolation and quantitative analysis of PD-L1 positive tumor-derived exosomes in clinics.

Switchable PAMAM megamers for deep tumor penetration and enhanced cell uptake

Nanoparticles fabricated to deliver anticancer drugs are usually designed to present optimized tumor penetration and cell internalization. However, there are some barriers and difficulties with most current technologies. Herein, size and charge switchable polyamidoamine (PAMAM) megamers (SChPMs) were prepared for the delivery of doxorubicin (DOX). SChPMs were fabricated by connecting PAMAM dendrimers with pH-sensitive bonds and surface PEGylation. At pH 7.4, the size and surface charge of these nanocarriers were approximately 100 nm and + 0.75 mV, but at the acidic extracellular pH of tumor cells (pH 6.5), their size were reduced dramatically (15 nm) and their surface charge increased to +6.7 mV. Cell studies confirmed that alteration of the size and surface charge enhanced their penetration into multicellular spheroids and cell internalization. These megamers, in addition to delivering the drug to the deeper areas of the tumor, could powerfully overcome physiological resistance to anthracycline-based drugs. The nanocarrier revealed enhanced antitumoral activity in animal studies. Toxicology studies and histopathological assessments of vital tissues of 4 T1 tumor bearing mice indicated minimal tissue damage when DOX-loaded SChPMs (DSChPMs) were used. It can be concluded that the versatile and agile nanocarriers developed in this study could be considered for further investigations into their clinical application.

The cardiac toxicity of PAMAM dendrimer drug delivery systems can be attenuated with the adjunct use of cardioprotective agents.

Polyamidoamine (PAMAM) dendrimer nanoparticles are efficient drug delivery vectors with potential clinical applications in nanomedicine. However, PAMAMs can compromise heart function, and strategies to mitigate cardiotoxicity would be beneficial. In this study, we investigated whether the adjunct use of three key cardioprotective agents could prevent the cardiac injury induced by a seventh-generation cationic PAMAM dendrimer (G7). Isolated rat hearts were subjected to ischemia and reperfusion (I/R) injury in the presence or absence of G7 or the cardioprotective agents Losartan, Epidermal Growth Factor (EGF), or S-nitroso-N-acetylpenicillamine (SNAP). I/R injury significantly compromised cardiac function, in terms of left ventricular hemodynamics, contractility, and vascular dynamics, which were markedly improved (p<0.05) by the administration of Losartan, EGF, or SNAP alone, confirming their cardioprotective effects. The administration of G7 significantly worsened cardiac function recovery following I/R(p<0.05). G7-induced impairments in cardiac and vascular dynamics were significantly improved by co-administration of Losartan, EGF, or SNAP. Treatment with G7 also significantly increased cardiac enzyme levels and infarct size, both of which were markedly reduced upon co-infusion of Losartan, EGF, or SNAP (p<0.05). Thus, G7 deteriorates the recovery of cardiac function in isolated hearts subjected to I/R injury, which can be rescued by co-administration of Losartan, EGF, or SNAP. These findings enhance our understanding of the nanotoxicology of PAMAM dendrimers in the mammalian heart and suggest that the adjunct use of cardioprotective agents is an effective strategy for mitigating the cardiotoxicity of these dendrimers and potentially other drug delivery systems.

The Importance of Biotinylation for the Suitability of Cationic and Neutral Fourth-Generation Polyamidoamine Dendrimers as Targeted Drug Carriers in the Therapy of Glioma and Liver Cancer.

In this study, we hypothesized that biotinylated and/or glycidol-flanked fourth-generation polyamidoamine (PAMAM G4) dendrimers could be a tool for efficient drug transport into glioma and liver cancer cells. For this purpose, native PAMAM (G4) dendrimers, biotinylated (G4B), glycidylated (G4gl), and biotinylated and glycidylated (G4Bgl), were synthesized, and their cytotoxicity, uptake, and accumulation in vitro and in vivo were studied in relation to the transport mediated by the sodium-dependent multivitamin transporter (SMVT). The studies showed that the human temozolomide-resistant glioma cell line (U-118 MG) and hepatocellular carcinoma cell line (HepG2) indicated a higher amount of SMVT than human HaCaT keratinocytes (HaCaTs) used as a model of normal cells. The G4gl and G4Bgl dendrimers were highly biocompatible in vitro (they did not affect proliferation and mitochondrial activity) against HaCaT and U-118 MG glioma cells and in vivo (against Caenorhabditis elegans and Wistar rats). The studied compounds penetrated efficiently into all studied cell lines, but inconsistently with the uptake pattern observed for biotin and disproportionately for the level of SMVT. G4Bgl was taken up and accumulated after 48 h to the highest degree in glioma U-118 MG cells, where it was distributed in the whole cell area, including the nuclei. It did not induce resistance symptoms in glioma cells, unlike HepG2 cells. Based on studies on Wistar rats, there are indications that it can also penetrate the blood-brain barrier and act in the central nervous system area. Therefore, it might be a promising candidate for a carrier of therapeutic agents in glioma therapy. In turn, visualization with a confocal microscope showed that biotinylated G4B penetrated efficiently into the body of C. elegans, and it may be a useful vehicle for drugs used in anthelmintic therapy.

Synthesis and characterization of mesoporous silicate as core and low generation polyamidoamine dendrimer as shell for delivery of 5-fluorouracil from their nano complex

Modern nanomedicine delivers drugs to malfunctioning cells. Several synthetic processes can change the shape, particle size, polydispersity index, surface area, and porosity of mesoporous silica nanoparticles (MSNs). Polyamidoamine (PAMAM) dendrimers are attractive polymers with circular forms, uniform distribution, well-structured branching, internal cavities, and surface terminal groups. The objective of this study is to deliver 5-fluorouracil (5-FU) as passive targeting to carcinogen cells via MSN-PAMAM-G3 nanoparticles. This study involved the direct and adaptable synthesis of MSN as the core vehicle, together with third-generation PAMAM dendrimers as the vehicle shell, with the goal of delivering the 5-FU in a targeted and controllable manner. Tetraethyl orthosilicate (TEOS) and cetyltrimethylammonium bromide (CTAB) are used as templates to make the center nanoparticle. Methyl acrylate (MA) and ethylenediamine (EDA) are monomers that cause the formation of branches in PAMAM. The obtained particles were fully characterized in terms of particle size, polydispersity index, zeta potential, thermal behavior, morphology, pore diameter, pore volume, and specific surface area. The particle size of MSN-PAMAM-G3s showed around 187.71 ± 3.97 nm, with a polydispersity index of 0.17 ± 0.01 and zeta potential of 32.17 ± 1.30 mV. By reducing the ratio of drug to vehicle from 1 to 0.25, a significant increase in the EE% of 5-FU from 21.36 ± 0.70 to 43.12 ± 0.67 was observed. The release of 5-FU from the vehicle (5-FU@MSN and 5-FU@MSN-PAMAM-G3) was shown to be considerably higher in an acidic medium (pH = 5.5) in comparison to a neutral medium (pH = 7.4) (P-value<0.05). Furthermore, in both acidic and neutral conditions, 5-FU release was sustained from the vehicle rather than the 5-FU solution. Our research revealed that the MSN-PAMAM-G3 nanoparticles effectively regulated the encapsulation and release of 5-FU, providing pH-sensitive and sustained medication delivery. It is asserted that this nanocarrier has the potential to effectively deliver 5-FU to cancer cells.

Effect of chromophore type on efficiency of reactive dye removal using polyamidoamine dendrimer

AbstractIn this study, by selecting a sample of dyes from a wide variety of chromophores used in the production of reactive dyes (monoazo, bisazo, metal azo, phthalocyanine, anthraquinone, copper formazan and triphendioxazine), the colour removal performance of polyamidoamine (PAMAM) dendrimer in reactive dyes was statistically evaluated depending on the dye chromophore groups (and accordingly molecular weight and number of sulfo groups of the dye), dendrimer concentration and centrifugation time. When all the results were examined, it was observed that the colour removal efficiency was significantly lower in metalazo and copper formazan‐based reactive dyes, whereas colour removals ranging from 93% to 98% could be obtained in bisazo, triphendioxazine, monoazo, anthraquinone and phthalocyanine dyes. With the use of dendrimer, the best colour removal efficiencies occurred at pH 3. However, it was found that the centrifugation time of 15 min is sufficient for all dyes, and a longer centrifugation does not provide any additional benefit in terms of colour removal.

Pharmacokinetic Assessments of Ursolic Loaded-Dendrimer Complex

Background: This study investigates the application of polyamidoamine (PAMAM) dendrimers as an innovative drug delivery approach for enhancing the pharmacokinetic profile of ursolic acid (UA), a pentacyclic triterpenoid with multifaceted therapeutic properties. UA, sourced from plants like Sanguisorba officinalis and Salvia officinalis, has been extensively studied for its pharmacological characteristics, including anti-inflammatory, antioxidant, and anti-diabetic properties, as recognized in Traditional Chinese Medicine (TCM). The clinical utility of UA is hampered by low bioavailability, which is attributed to its hydrophobic nature. To address this limitation, we explore the use of PAMAM dendrimers, known for their drug delivery potential. Methods: The UA-PAMAM G0 dendrimers were synthesized with varying molar ratios. Characterization included size analysis, PDI, and zeta potential determination. FTIR confirmed the chemical structure. Male SD rats were acclimatized and administered UA control suspension and UA-G0 dendrimer complex orally. Blood samples were collected for pharmacokinetic analysis. The study obtained IAEC approval. Results: The UA-PAMAM G0 dendrimer complexes exhibited varying sizes based on molar ratios, with the 2:1 ratio showing significantly smaller dimensions. FTIR confirmed successful conjugation. In the pharmacokinetic study, the UA-G0 dendrimer complex demonstrated higher plasma concentrations than UA alone, as indicated by increased Cmax and AUC values. The results suggest enhanced oral delivery and bioavailability of UA in the dendrimer complex. Conclusion: This study demonstrated the successful synthesis of UA-PAMAM G0 dendrimer complexes with size variations based on molar ratios. The pharmacokinetic analysis revealed improved plasma concentrations and bioavailability of UA in the dendrimer complex compared to UA alone. These findings highlight the potential of PAMAM dendrimers for enhancing the oral delivery of hydrophobic compounds like UA, bridging the gap between traditional herbal medicine and modern drug delivery strategies. Further research can explore the broader applications of such dendrimer complexes in drug delivery systems.