Generation Polyamidoamine Dendrimers Research Articles

Catalytic Application of Copper Complex Prepared by a NNN Pincer Ligand Supported on Silica Nanoparticles Using first Generation of Polyamidoamine Dendrimers

Catalytic Application of Copper Complex Prepared by a NNN Pincer Ligand Supported on Silica Nanoparticles Using first Generation of Polyamidoamine Dendrimers

Synthesis and characterization of Fulvestrant and Paclitaxel conjugates with polyamidoamine dendrimer fourth generation

Introduction and aim. Poorly soluble anticancer drugs can be attached covalently into biologically inert macromolecule in order to administrate a drug as water soluble form. It was proven that covalent linkers, for instance amide or carbamate bonds are susceptible to hydrolysis. Thus the attached drug can be released from the conjugates in tissue, specifically within the targeted cell. We aimed at construction of water soluble conjugates of Fulvestrant and Paclitaxel with PAMAM G4 dendrimer. In order to obtain water soluble conjugates the amine groups were substituted with R-glycidol. Material and methods. Polyamidoamine dendrimer of fourth generation was synthesized and examined by detailed NMR analysis in water and in DMSO. The conjugates were covalently linked to amine groups of PAMAM after activation of Fulvestrant 17-OH group with 4-nitrophenylchloroformate and activation of end-carboxyl group of Paclitaxel succinate. Results. The method of binary conjugate PAMAMG4-Fulvestrant-Paclitaxel synthesis was elaborated and the product was characterized by physicochemical methods. Conclusion. The glycidylated PAMAMG4-Fulvestrant-Paclitaxel conjugate is better soluble in water than unconverted drugs.

Improved biocompatibility of dendrimer-based gene delivery by histidine-modified nuclear localization signals

Polyamidoamine (PAMAM) dendrimers have been explored as an alternative to polyethylenimine (PEI) as a gene delivery carrier because of their relatively low cytotoxicity and excellent biocompatibility. The transfection efficiency of PAMAM dendrimers can be improved by the addition of nuclear localization signal (NLS), a positively charged peptide sequence recognized by cargo proteins in the cytoplasm for nuclear transport. However, increased positive charges from NLS can cause damage to the cytoplasmic and mitochondrial membranes and lead to reactive oxygen species (ROS)-induced cytotoxicity. This negative effect of NLS can be negated without a significant reduction in transfection efficiency by adding histidine, an essential amino acid known as a natural antioxidant, to NLS. However, little is known about the exact mechanism by which histidine reduces cytotoxicity of NLS-modified dendrimers. In this study, we selected cystamine core PAMAM dendrimer generation 2 (cPG2) and conjugated it with NLS derived from Merkel cell polyomavirus large T antigen and histidine (n = 0–3) to improve transfection efficiency and reduce cytoxicity. NLS-modified cPG2 derivatives showed similar or higher transfection efficiency than PEI 25 kDa in NIH3T3 and human mesenchymal stem cells (hMSC). The cytotoxicity of NLS-modified cPG2 derivatives was substantially lower than PEI 25 kDa and was further reduced as the number of histidine in NLS increased. To understand the mechanism of cytoprotective effect of histidine-conjugated NLS, we examined ROS scavenging, hydroxyl radical generation and mitochondrial membrane potential as a function of the number of histidine in NLS. As the number of hisidine increased, cPG2 scavenged ROS more effectively as evidenced by the hydroxyl radical antioxidant capacity (HORAC) assay. This was consistent with the reduced intracellular hydroxyl radical concentration measured by 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) assay in NIH3T3. Finally, fluorescence imaging with JC-1 confirmed that the mitochondrial membranes of NIH 3T3 were well-protected during the transfection when NLS contained histidine. These experimental results confirm the hypothesis that histidine residues scavenge ROS that is generated during the transfection process, preventing the excessive damage to mitochondrial membranes, leading to reduced cytotoxicity.

Synthesis of guanidinium‐dendrimer‐type pDNA carriers for gene delivery into floating blood cells

AbstractGuanidinium‐dendrimer‐type pDNA carriers have been synthesized for gene delivery into floating blood cells. A 2nd generation polyamidoamine (PAMAM‐G2) dendrimers were modified with guanidinium groups at the primary amine. The resulting PAMAM‐G2‐Gu dendrimer with a modification degree of 53 mol%, PAMAM‐G2‐Gu(53), formed polyion complexes (PICs) above a mixing positive/negative charge ratio (+/−) of 64. The resulting PAMAM‐G2‐Gu(53)/pDNA PIC was stable for 24 h in the presence of 10% fetal bovine serum and exhibited no significant cytotoxicity against HL‐60 human leukemia cells during the above incubation. It is worth noting that the PAMAM‐G2‐Gu(53)/pDNA PIC at mixing positive/negative (+/−) charge ratio of 64 mediated the highest gene expression among all PICs in this study such as an unmodified PAMAM‐G2, the PAMAM‐G2 modified with diethylaminoethyl groups (PAMAM‐G2‐DEAE). Especially, the resulting gene expression was higher than commercially available branched poly(ethylenimine) (b‐PEI). Consequently, the PAMAM‐G2‐Gu(53)/pDNA PIC is effective for gene delivery to floating blood cells and is expected to be applied to ex vivo transfection.

Polyamidoamine with a hyper-branched structure grafted on modified magnetic graphene oxide for the trace separation of diclofenac and acetaminophen followed by high-performance liquid chromatography determination

Different generations of polyamidoamine dendrimers were synthesized on a focal core of magnetic graphene oxide modified with 3-aminopropyltriethoxysilane. After the characterization of synthesized dendrimers, its second generation was employed as a suitable sorbent for simultaneous separation/preconcentration of diclofenac and acetaminophen by a dispersive magnetic solid phase microextraction. The extracted analytes were then quantified by high-performance liquid chromatography with ultraviolet detection. Under optimized conditions, the limits of detection were 0.3 µg/L for diclofenac and 0.1 µg/L for acetaminophen. The intra-day relative standard deviations at 50 μg L−1 levels were 1.8% for diclofenac and 2.1% for acetaminophen, while the inter-day relative standard deviations were 3.6% and 4.5% for diclofenac and acetaminophen, respectively. The calibration graphs were linear in ranges of 1.0–500.0 µg/L and 0.5–600.0 µg/L for diclofenac and acetaminophen, respectively, with good coefficients of determination (r2 > 0.998). The method was successfully applied to the determination of diclofenac and acetaminophen in water, milk, and biological samples.

Gene Delivery into T cells using Ternary Complexes of DNA, Lipofectamine, and Carboxy-terminal Phenylalanine-modified Dendrimers.

T-cells play critical roles in various immune reactions, and genetically engineered T-cells have attracted attention for the treatment of cancer and autoimmune diseases. Previously, we showed that a polyamidoamine dendrimer of generation 4 (G4), modified with 1,2-cyclohexanedicarboxylic anhydride (CHex) and phenylalanine (Phe) (G4-CHex-Phe), was useful for delivery into T cells and their subsets. In this study, we constructed an efficient non-viral gene delivery system using this dendrimer. Ternary complexes were prepared using different ratios of plasmid DNA, Lipofectamine, and G4-CHex-Phe. A carboxyl-terminal dendrimer lacking Phe (G3.5) was used for comparison. These complexes were characterized using agarose gel electrophoresis, dynamic light scattering, and ζpotential measurements. In Jurkat cells, the ternary complex with G4-CHex-Phe at a P/COOH ratio of 1/5 showed higher transfection activity than other complexes such as binary and ternary complexes with G3.5 and without any significant cytotoxicity. The transfection efficiency of the G4-CHex-Phe ternary complexes decreased considerably in the presence of free G4-CHex-Phe and on altering the complex preparation method. These results suggest that G4-CHex-Phe promotes the cellular internalization of the complexes, which is useful for gene delivery into T cells. This article is protected by copyright. All rights reserved.

Erlotinib-Loaded Dendrimer Nanocomposites as a Targeted Lung Cancer Chemotherapy.

Lung cancer is the main cause of cancer-related mortality globally. Erlotinib is a tyrosine kinase inhibitor, affecting both cancerous cell proliferation and survival. The emergence of oncological nanotechnology has provided a novel drug delivery system for erlotinib. The aims of this current investigation were to formulate two different polyamidoamine (PAMAM) dendrimer generations-generation 4 (G4) and generation 5 (G5) PAMAM dendrimer-to study the impact of two different PAMAM dendrimer formulations on entrapment by drug loading and encapsulation efficiency tests; to assess various characterizations, including particle size distribution, polydispersity index, and zeta potential; and to evaluate in vitro drug release along with assessing in situ human lung adenocarcinoma cell culture. The results showed that the average particle size of G4 and G5 nanocomposites were 200 nm and 224.8 nm, with polydispersity index values of 0.05 and 0.300, zeta potential values of 11.54 and 4.26 mV of G4 and G5 PAMAM dendrimer, respectively. Comparative in situ study showed that cationic G4 erlotinib-loaded dendrimer was more selective and had higher antiproliferation activity against A549 lung cells compared to neutral G5 erlotinib-loaded dendrimers and erlotinib alone. These conclusions highlight the potential effect of cationic G4 dendrimer as a targeting-sustained-release carrier for erlotinib.

Synthesis and characterization of low generation polyamidoamine dendrimers and release of 5‐fluorouracil from their complexes

AbstractThe aim of this work was to investigate the potential of low‐generation polyamidoamine (PAMAM) dendrimers as drug nanocarriers for 5‐fluorouracil (5‐FU), an anticancer drug, and to determine the type of dendrimer generation (half or full) with the highest drug load capacity and slowest release rate. For this, PAMAM dendrimers (up to 2.0 generation) were synthesized and characterized by means of spectroscopic techniques and thermal analysis. Then, 5‐FU was successfully incorporated into dendrimers, and the resulting complexes were characterized in terms of their, elemental composition, spectroscopy, thermal behavior, and loading efficacy. In addition, in vitro release studies of 5‐fluorouracil from complexes were conducted using phosphate‐buffered saline; and the 5‐FU release kinetics was also modeled. The successful synthesis of PAMAM dendrimers was confirmed by Fourier transform infrared spectroscopy (FTIR), 1H‐NMR, UV–vis, dynamic light scattering and thermogravimetric analysis (TGA) analysis. Energy‐dispersive X‐ray spectroscopy (EDX), FTIR, UV–vis and TGA results confirmed the complexation phenomena among PAMAM dendrimers and 5‐FU drug. It was found that the encapsulation efficiency and drug release rate are a function of generation type, and that the full‐generation dendrimers showed the best results. The Korsmeyer‐Peppas model best described the kinetics of drug release for all complexes. These results confirm that the proposed low‐generation dendrimers are suitable polymeric nanocarriers for drug delivery applications.

Abstract 1997: 2C5 antibody modified dendrimer-based mixed micelles for the treatment of multidrug resistant cancers

Abstract Purpose: A major hurdle in chemotherapy is multidrug resistance (MDR) observed in tumors. Downregulation of efflux proteins such as P-glycoprotein (P-gp) using small interfering RNA (siRNA) can be an effective way to treat resistant tumors. In this study, monoclonal antibody 2C5 (mAb 2C5) - PEG7k-DOPE conjugates were post-inserted into the mixed dendrimer micelles containing generation 4 (G4) polyamidoamine (PAMAM)-PEG2k-DOPE and PEG5k-DOPE. The inherent amphiphilic nature of DOPE conjugates causes the copolymers to self-assemble to form a micelle and encapsulate hydrophobic chemotherapeutic drug in its core. The siRNA electrostatically binds to the cationic charges on the G4 PAMAM dendrimer. The tumor-specific mAb 2C5 on the surface of these nano-preparations resulted in improved tumor targeting. Methods: G4 PAMAM-PEG2k-DOPE was prepared by conjugating G4 PAMAM with para-nitrophenol (pNP)-PEG2k-DOPE. To prepare 2C5-PEG7k-DOPE, mAb 2C5 was mixed with micelles containing pNP-PEG7k-DOPE and PEG5k-DOPE in sodium citrate buffer at pH 5.0 and later adjusted the pH to 8.0. In vitro evaluation of the targeted and non-targeted micelles were performed in both MDA-MB-231 and SKOV-3TR resistant cell lines. Further a xenograft MDA-MB-231 in vivo mice tumor models were performed. Results: The 2C5-conjugated mixed dendrimer micelles have a uniform size distribution with a slightly positive zeta potential. They show a stable size and zeta potential for 20 days. The morphology of the 2C5 modified micelles was confirmed using TEM imaging. A higher cellular association was observed in the micelles with the 2C5 antibody targeting using fluorescence imaging (DOPE-FITC tagged micelle) in both the cell lines. At 30 minutes the 2C5 targeted mixed dendrimer micelles showed high cellular uptake and was analyzed using flow cytometry. We further evaluated the P-gp downregulation using western blot and observed a significant downregulation of P-gp levels in the targeted formulation versus the non-targeted formulation. The in vivo tumor growth inhibition study in nude NCG 572 MDA-MB-231 tumor bearing mice showed that the immuno-micelles loaded with siMDR-1 and chemotherapeutics resulted in significantly increased therapeutic efficacy compared to non-modified mixed dendrimer micelles. Conclusions: We have evaluated the 2C5 antibody-modified mixed dendrimer micelles in different cell models, in addition to the models tested in our previous studies. We have successfully established the stability of the formulation in this study and established a 20-day shelf-life. Cellular association, internalization and P-gp downregulation studies show the superiority of the 2C5 modified dendrimer micelles upon non-targeted preparations or free actives. Citation Format: Satya Siva Kishan Yalamarty, Nina Filipczak, Xiang Li, Tanvi Vinod Pathrikar, Colin Cotter, Vladimir P. Torchilin. 2C5 antibody modified dendrimer-based mixed micelles for the treatment of multidrug resistant cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1997.

Electrospun nanofibers of cellulose acetate/metal organic framework-third generation PAMAM dendrimer for the removal of methylene blue from aqueous media

In this research, magnetic metal–organic framework nanofibers were produced by the electrospinning method. The nanocomposite was functionalized by third generation hyperbranched poly(amidoamine) dendrimer (PAMAM) to improve its dye adsorption efficiency from aqueous media. The characteristics of the synthesized magnetic nanocomposite was determined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) along with elemental mapping analysis and scanning electron microscopy (SEM). Central composite design (CCD) based on response surface methodology (RSM) was performed to optimize the adsorption variables and the values of coefficient of determination (R2) and adjusted R2 were 0.9837 and 0.9490, respectively. The results obtained demonstrated remarkable properties of the synthesized nanofiber as adsorbent for methylene blue from aqueous solutions with the removal efficiency of 95.37% and maximum methylene blue (MB) adsorption capacity of 940.76 mg g−1 under optimized conditions. In addition, it was shown that kinetics and adsorption isotherm of the dye removal process followed Langmuir and pseudo-second-order models, respectively. Thermodynamic study of the dye removal indicated that the process was spontaneous and favorable at higher temperatures. Also, the reusability study shows favorable dye removal efficiency of 80.67% even after 4 cycles. To investigate the performance of the adsorbent for the removal of MB in real samples, a sewage sample from a local hospital was used. The result showed good efficiency of the adsorbent.

Cytarabine and dexamethasone-PAMAM dendrimer di-conjugate sensitizes human acute myeloid leukemia cells to apoptotic cell death

Polyamidoamine (PAMAM) dendrimers are widely used as a part of drug delivery systems (DDS) to improve anticancer drug bioavailability. In the present study, monophosphates of nucleosides, anti-nucleosides (cytarabine, C and fludarabine, F) and synthetic glucocorticoid dexamethasone (D) were attached to the third generation (G3) PAMAM dendrimer via phosphamide pH-sensitive linker. Conjugates were found to be stable at neutral pH, whereas acid-triggered hydrolysis of phosphamide bond was observed at pH 5. The anticancer action of selected biotinylated mono- and di-conjugates, namely CP-, FP-, DP-CP- and DP-FP-PAMAM dendrimers was then compared to cytotoxic activity of free drugs using four cellular models of leukemia in vitro, i.e., K-562, LAMA-84, THP-1 and HL-60 cells. 10 nM DP-CP-conjugate lowered metabolic activity, caused G0/G1 cell cycle arrest and induced apoptotic cell death in HL-60 cells compared to non-cytotoxic and non-cytostatic action of free drugs when used at the same concentration. 10 nM CP-, DP-FP- and FP-conjugates also promoted a decrease in metabolic activity in K-562, LAMA-84, and THP-1 and HL-60 cells, respectively, however, without a sign of cytotoxicity. In conclusion, we show that the anticancer potential of CP and FP in leukemia cells may be enhanced by the conjugation with PAMAM dendrimers, especially in the presence of DP in selected experimental settings.

Orchestrated Cytosolic Delivery of Antigen and Adjuvant by Manganese Ion-Coordinated Nanovaccine for Enhanced Cancer Immunotherapy.

Cancer vaccines have received tremendous attention in cancer immunotherapy due to their capability to induce a tumor-specific immune response. However, their effectiveness is compromised by the insufficient spatiotemporal delivery of antigens and adjuvants in the subcellular level to induce a robust CD8+ T cell response. Herein, a cancer nanovaccine G5-pBA/OVA@Mn is prepared through multiple interactions of manganese ions (Mn2+), benzoic acid (BA)-modified fifth generation polyamidoamine (G5-PAMAM) dendrimer, and the model protein antigen ovalbumin (OVA). In the nanovaccine, Mn2+ not only exerts a structural function to assist OVA loading as well as its endosomal escape, but works as an adjuvant of stimulator of interferon genes (STING) pathway. These collaboratively facilitate the orchestrated codelivery of OVA antigen and Mn2+ into cell cytoplasm. Vaccination with G5-pBA/OVA@Mn not only shows a prophylactic effect, but also significantly inhibits growth against B16-OVA tumors, indicating its great potential for cancer immunotherapy.

Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines.

Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance. In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifically and stay stable in the circulation longer. In order to determine whether conjugate selectivity can be increased for the specific drug type, we have reported different strategies for loading and conjugation of Palbociclib to different generations of magnetic PAMAM dendrimers. The best method leading to the highest amount of Palbociclib conjugation was chosen, and the characterization of the Palbociclib conjugated dendrimeric magnetic nanoparticles (PAL-DcMNPs) were performed. In vitro pharmacological activity of the conjugation was demonstrated by measuring the cell viability and lactate dehydrogenase (LHD) release. Obtained results indicated that PAL-DcMNPs treatment of the breast cancer cell lines, leads to an increase in cell toxicity compared to free Palbociclib. The observed effects were more evident for MCF-7 cells than for MDA-MB231 and SKBR3 cells, considering that viability decreased to 30% at 2.5µM treatment of PAL-DcMNPs at MCF-7 cells. Finally, in Palbociclib and PAL-DcMNPs treated breast cancer cells, the expression levels of some pro-apoptotic and drug resistance related genes were performed by RT-PCR analysis. Our knowledge indicates that the proposed approach is novel, and it can provide new insight into the development of Palbociclib targeting delivery system for cancer treatment.

Preclinical evaluation of modified carbon nanohorns and their complexation with insulin.

The current study emphasizes the minimal toxicity observed in vitro and in vivo for carbon nanohorns (CNHs) modified with third generation polyamidoamine (PAMAM) dendrimers. Initially, we investigated the interactions between CNH-PAMAM and lipid bilayers, which were utilized as representative models of cellular membranes for the evaluation of their toxicity in vitro. We found that the majority of those interactions occur between the modified CNHs and the polar groups of phospholipids, meaning that CNH-PAMAM does not incorporate into the lipid chains, and thus, disruption of the lipid bilayer structure is avoided. This outcome is a very important observation for further evaluation of CNH-PAPAM in cell lines and in animal models. Next, we demonstrated the potential of CNH-PAMAM for complexation with insulin, as a proof of concept for its employment as a delivery platform. Importantly, our study provides comprehensive evidence of low toxicity for CNH-PAMAM both in vitro and in vivo. The assessment of cellular toxicity revealed that the modified CNHs exhibited minimal toxicity, with concentrations of 151 μg mL-1 and 349 μg mL-1, showing negligible harm to EO771 cells and mouse embryonic fibroblasts (MEFs), respectively. Moreover, the histological analysis of the mouse livers demonstrated no evidence of tissue necrosis and inflammation, or any visible signs of severe toxicity. These findings collectively indicate the safe profile of CNH-PAMAM and further contribute to the growing body of knowledge on the safe and efficient utilization of CNH-based nanomaterials in drug and protein delivery applications.

Immobilization of Alcalase on Silica Supports Modified with Carbosilane and PAMAM Dendrimers.

Enzyme immobilization is a powerful strategy for enzyme stabilization and recyclability. Materials covered with multipoint molecules are very attractive for this goal, since the number of active moieties to attach the enzyme increases with respect to monofunctional linkers. This work evaluates different dendrimers supported on silica to immobilize a protease enzyme, Alcalase. Five different dendrimers were employed: two carbosilane (CBS) dendrimers of different generations (SiO2-G0Si-NH2 and SiO2-G1Si-NH2), a CBS dendrimer with a polyphenoxo core (SiO2-G1O3-NH2), and two commercial polyamidoamine (PAMAM) dendrimers of different generations (SiO2-G0PAMAM-NH2 and SiO2-G1PAMAM-NH2). The results were compared with a silica support modified with a monofunctional molecule (2-aminoethanethiol). The effect of the dendrimer generation, the immobilization conditions (immobilization time, Alcalase/SiO2 ratio, and presence of Ca2+ ions), and the digestion conditions (temperature, time, amount of support, and stirring speed) on Alcalase activity has been evaluated. Enzyme immobilization and its activity were highly affected by the kind of dendrimer and its generation, observing the most favorable behavior with SiO2-G0PAMAM-NH2. The enzyme immobilized on this support was used in two consecutive digestions and, unlike CBS supports, it did not retain peptides released in the digestion.

Development and optimization of RofA-PAMAM dendrimer complex materials for sustained drug delivery

The current indagation is observed on anatomization of drug release dynamics aiming at preceding the anti-inflammation activity of roflumilast analogue (RofA), post assemblage with dendrimer. The study pondered the development and optimization of RofA-Dendrimer complexes for sustained delivery. Many physiological and physicochemical factors, like encapsulation potency, drug loading, drug release, dissolvability, stability, and anti-inflammation activity were determined. The study results in the observation of encapsulation potency of 72.64 ± 0.189%, loading capability of 63.41 ± 0.166%, and in vitro release of RofA-4.0 G PAMAM complex was found to increase making it an appropriate candidate for sustained drug release progressively . It has been found by constructing drug release kinetics, that the release followed was a non- fickian diffusion ( n<0.89). The phase solubility diagram indicated an increment of solubility of RofA with varied dendrimer generation as well as pH. The study was initiated to prepare a suited candidate fit to scale back site-specific inflammation. Further concluding the contemplation for its sustained delivery, enhanced solubility, and potentially augmented anti-inflammation activity. • The aims of this study were to assess the potentially augmented effect of roflumilast analogue post assemblage with different generations of polyamidoamine dendrimer. • In this study, RofA-Dendrimer complexes, with RofA as the model drug, the encapsulation potency, loading capacity, in vitro drug release behavior, and stability were studied. • The effect of the concentration of varied generations of PAMAM dendrimer on the solubility of RofA has been discussed in detail. • We also examined the anti-inflammatory activity and sought to determine the inhibitory effect on protein denaturation. • The results were affirmed by the determination of n value i.e. hill coefficient with respect to the substrate concentration and rate of inhibition. • The impact of adjuvant antibiotic therapy was also explored by the means of a cytotoxicity assay.

Toxicity of polyamidoamine dendrimers in vivo

The development of effective drug delivery systems is a crusial task for modern medicine. The main problem is the occurrence of non-specific toxicity leading to undesirable side effects in vivo.This article aims at reviewing resent research on the toxicity of polyamidoamine (PAMAM) dendrimers in vivo. The research results show that the toxicity of PAMAM dendrimers and modified nanoparticles depends both on the characteristics of the particles themselves (size, generation and surface charge) and on the administration parameters. It has been shown that cationic PAMAM dendrimers of small and medium generations are non-toxic in vivo when administered intravenously and intraperitoneally to mice at doses up to 10 mg/kg. In turn, anionic, neutral, and modified PAMAM dendrimers do not exhibit toxicity, regardless of the route of administration. Thus, by varying methods of administration, the dose, and modifying the surface of dendrimers, the decrease in toxicity can be achieved, promising a path towards their successfully aplication as drug carriers.

Synthesis and characterization of fluorescence poly(amidoamine) dendrimer-based pigments

In this work, we looked at how to make fluorescence hybrid poly(amidoamine) dendrimer (PAMAM) dendrimers using calcozine red 6G and coumarin end groups. After synthesis of ethylenediamine (EDA)-cored 4th generation PAMAM dendrimer (G4.0), surface functional groups is reacted with calcozine red 6G (Rh6G) and 7-methacryloyloxy-4-methylcoumarin. Fourier transform infrared spectroscopy, proton nuclear magnetic resonance (1H NMR), and X-ray diffraction are used to characterize the structure of synthesized fluorescent hybrid dendrimers. Optical properties are demonstrated using a fluorescence spectrophotometer, and UV–Vis–NIR reflectance spectra. According to UV–Vis–NIR reflectance spectra, hybrid dendrimers were transparent in the NIR range. Moreover, quantum yield (Φs) of hybrid dendrimers was calculated in dimethylformamide (DMF), ethanol, dimethyl sulfoxide (DMSO), and distilled water (H2O). Dendrimers in which Rh6G was utilized to modification showed the maximum quantum yield in ethanol due to great interaction of structure with ethanol and the arrangement of ring-opened amide shape of calcozine red 6G.

Lipophilic PAMAM Dendrimer: Conceptualization of Targeted Cosmetics and Drug Delivery

Abstract: The structure, properties, synthesis, negligible toxicity, and surface modification of PAMAM (polyamidoamine dendrimers) are all discussed in this review. The properties of supramolecular PAMAM dendrimers in nanopolymer science have shown great progress in delivering medicines. A divergent strategy was used to construct a Generation four (G4.0) PAMAM dendrimer with an ethylenediaminetetraacetic acid core and repeating units of acrylic acid and ethylenediamine. PAMAM dendrimers, have an aminodoamine repeat branching architecture that starts with an ethylene diamine initiator core. A generation [G] is a set of branching steps that follow each other. Drug molecules can be transferred either as covalently bonded to the functional groups on the dendrimer surface or by forming non-covalent complexes with dendrimers. Full generation PAMAM dendrimers are terminated with amine surface [G0, G1, G2, G3, G4], whereas half-generation dendrimers are terminated with carboxylate [G1.5, G2.5, etc]. PAMAM dendrimers appear to have negligible toxicity and immunogenicity, as well as favorable biodistribution-: according to the current study they can improve drug solubility, prevent drug degradation, increase circulation time, and potentially target drugs. According to the characterization study, they exhibit strong lipophilic qualities, allowing them to easily pass the blood-brain barrier. Due to cheaper polydispersity index of dendrimers, they possess greater stability and the void spaces of dendrimers are accessible for drug loading. The existence of a duplet functional group on the dendrimers enables appending vectors, ligands and devices for targed the drug delivery in the body.

Co-Delivery of siRNA and Chemotherapeutic Drug Using 2C5 Antibody-Targeted Dendrimer-Based Mixed Micelles for Multidrug Resistant Cancers.

Multidrug resistance (MDR) observed in tumors significantly hinders the efficacy of chemotherapy. Downregulation of efflux proteins, such as P-glycoprotein (P-gp), using small interfering RNA (siRNA) can be an effective way to minimize the resistance in tumors. In this study, monoclonal antibody 2C5 (mAb 2C5)-PEG7k-DOPE conjugates were post-inserted into the mixed dendrimer micelles containing generation 4 (G4) polyamidoamine (PAMAM)-PEG2k-DOPE and PEG5k-DOPE. The inherent amphiphilic nature of DOPE conjugates causes the copolymers to self-assemble to form a micelle, which can encapsulate hydrophobic chemotherapeutic drugs in its core. The siRNA electrostatically binds to the cationic charges on the G4 PAMAM dendrimer. The tumor-specific mAb 2C5 on the surface of these nano-preparations resulted in improved tumor targeting. This active targeting to tumors can cause increase in the drug and siRNA accumulation at the tumor site, and thereby minimizing the off-target effects. The micelles were shown to have higher cellular association and effectiveness in vitro. The immunomicelle preparation was also tested for cytotoxicity in breast (MDA-MB-231) and ovarian (SKOV-3TR) MDR cancer cell lines.