Polyamidoamine Dendrimers Research Articles

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.

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.

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.

Polyamidoamine dendrimer conjugated with novel scorpion venom peptide as a promising targeted delivery system for glioblastoma

Polyamidoamine dendrimer conjugated with novel scorpion venom peptide as a promising targeted delivery system for glioblastoma

Injectable Dendrimer Hydrogel Delivers Melphalan in Both Conjugated and Free Forms for Retinoblastoma.

We report the successful synthesis of an injectable dendrimer hydrogel (DH) carrying melphalan, a clinical drug for retinoblastoma treatment, in both conjugated and free forms. Polyamidoamine (PAMAM) dendrimer generation 5 (G5) is surface-modified with an acid-sensitive acetal-dibenzocyclooctyne linker and then undergoes azide-alkyne cycloaddition with melphalan-PEG-N3 conjugate to form G5-acetal-melphalan. During the DH gelation between G5-acetal-melphalan and PEG-diacrylate, free melphalan is added, resulting in a hydrogel (G5-acetal-melphalan-DH/melphalan) that carries the drug in both conjugated and free forms. Melphalan is slowly released from G5-acetal-melphalan-DH/melphalan, with the conjugated melphalan released more quickly at pH 5.3 due to acid-triggered acetal bond cleavage. The formulation's in vitro safety and efficacy were established on human corneal epithelia (HCE-2) and retinoblastoma cells (Y79). In an in vivo Y79 tumor xenograft model of retinoblastoma, intratumorally injected G5-melphalan-DH formulation prolonged tumor suppression. This injectable, multimodal, pH-responsive formulation shows promise for intravitreal injection to treat retinoblastoma.

Graphene Oxide‐Incorporated Polylactic Acid/Polyamidoamine Dendrimer Electroconductive Nanocomposite as a Promising Scaffold for Guided Tissue Regeneration

AbstractIn the recent years, electroconductive scaffolds have shown promising capabilities in guided regeneration of electroactive tissues including nerve, heart muscle, bone, cartilage, and skin. Herein, the fabrication of a novel electroconductive poly (L‐lactic acid) (PLLA)/polyamidoamine (PAMAM) dendrimer nanofibrous scaffold containing graphene oxide (GO) nanosheets is described. The presence of PAMAM with amine terminal groups successfully aminolyzed PLLA. Interestingly, both PAMAM (5% w/w) and GO (0.5, 1, 2% w/w) not only contributed to reducing the fiber diameter, increasing the hydrophilicity and degradation rate, but also provided a nanocomposite scaffold with enhancement in electrical conductivity. By incorporating 1% w/w of GO, the nanocomposite scaffold exhibited optimized properties, including electrical conductivity (≈3.09 × 10−5 S m−1), crystallinity (≈ 47%), Young's modulus (≈16.95 MPa), as well as strength (≈1.58 MPa). This nanocomposite also demonstrated significant antibacterial activity of ≥ 90% against both gram‐positive and gram‐negative bacteria. Cellular assays confirmed acceptable cytocompatibility of the nanocomposite scaffolds containing GO and PAMAM, which can support the viability and proliferation of PC‐12 cells. In conclusion, the presence of GO nanosheets alongside PAMAM dendrimers can synergically promote the properties of the prepared nanofibrous mats which can be used as potential electroconductive scaffolds for guided tissue regeneration.

Controlling Alveolar Bone Loss by Hydrogel‐Based Mitigation of Oral Dysbiosis and Bacteria‐Triggered Proinflammatory Immune Response

AbstractPeriodontitis is a chronic infection where abnormal host‐microbiota interactions alter the oral microbiome, trigger a proinflammatory immune response, and cause inflammatory alveolar bone loss. While antibiotics are occasionally necessary for treating periodontitis, their use must be carefully managed to prevent the development of drug resistance and oral dysbiosis. Therefore, it's crucial to develop new treatment strategies for periodontitis that reduce antibiotic dependence while effectively controlling the inflammation triggered by bacteria. In this study, a hydrogel is engineered by grafting cationic polyamidoamine dendrimers (PAMAM‐G3) onto the oxidized carboxymethyl cellulose (OCMC) backbone, resulting in an injectable cationic hydrogel (OCMC‐PAMAM‐G3, O‐P). This hydrogel can capture anionic microbial‐associated molecular patterns (MAMPs), such as lipopolysaccharides (LPS) and cell‐free DNA (cfDNA). These findings reveal that using O‐P application circumvents the disruption of the oral mucosa microbiome caused by traditional antibiotics. Additionally, this hydrogel can mitigate inflammatory alveolar bone loss in a ligature‐induced periodontitis mouse model by alleviating the LPS/cfDNA‐TLR4/9 pathway. Moreover, topical administration of O‐P hydrogel has no significant adverse effects on the oral mucosa microbiome while improving the local subgingival microbiome. The study highlights a strategy targeting MAMPs while avoiding antibiotics, as it can mitigate the bacteria‐triggered proinflammatory immune response and potentially preserve oral dysbiosis.

Fast and efficient synthesis of polymers driven by solar radiation. New insights on dye/dendrimer photoinitiating systems

The performance of a series of visible-light driven photoinitiating systems (Vis-PIs) for radical polymerization was evaluated. The Vis-PIs formulations consisted of aqueous solutions containing xanthene dyes as sensitizers, while polyamido-amine (PAMAM) dendrimers were tested as alternative co-initiators of lower toxicity than the traditional amines. Acrylamide and HEMA were used as probe monomers and the respective polymers were characterized by FTIR, DSC and viscosimmetry. In order to elucidate the mechanism of photopolymerization, the triplet excited-states and semirreduced forms of the dyes were characterized by transient spectroscopy. Photophysical parameters as intersystem crossing and radical quantum yields were also determined for each dye/dendrimer couple. All Vis-PIs operated successfully under solar irradiation, achieving high monomer conversions after short exposure times. Interestingly, formulations with partially halogenated dyes showed the highest efficiency, which correlates inversely with the affinity and the electron transfer capability between the reactants. This study demonstrates the usefulness of dye/dendrimer combinations to operate as efficient aqueous Vis-PIs under an inexpensive, unlimited and natural energy source such as sunlight.

A Novel PAMAM G3 Dendrimer-Based Foam with Polyether Polyol and Castor Oil Components as Drug Delivery System into Cancer and Normal Cells.

One of the intensively developed tools for cancer therapy is drug-releasing matrices. Polyamidoamine dendrimers (PAMAM) are commonly used as nanoparticles to increase the solubility, stability and retention of drugs in the human body. Most often, drugs are encapsulated in PAMAM cavities or covalently attached to their surface. However, there are no data on the use of PAMAM dendrimers as a component of porous matrices based on polyurethane foams for the controlled release of drugs and biologically active substances. Therefore, in this work, porous materials based on polyurethane foam with incorporated third-generation poly(amidoamine) dendrimers (PAMAM G3) were synthesized and characterized. Density, water uptake and morphology of foams were examined with SEM and XPS. The PAMAM was liquefied with polyether polyol (G441) and reacted with polymeric 4,4'-diphenylmethane diisocyanate (pMDI) in the presence of silicone, water and a catalyst to obtain foam (PF1). In selected compositions, the castor oil was added (PF2). Analogs without PAMAM G3 were also synthesized (F1 and F2, respectively). An SEM analysis of foams showed that they are composed of thin ribs/walls forming an interconnected network containing hollow bubbles/pores and showing some irregularities in the structure. Foam from a G3:G441:CO (PF2) composition is characterized by a more regular structure than the foam from the composition without castor oil. The encapsulation efficiency of drugs determined by the XPS method shows that it varies depending on the matrix and the drug and ranges from several to a dozen mass percent. In vitro biological studies with direct contact and extract assays indicated that the F2 matrix was highly biocompatible. Significant toxicity of dendrimeric matrices PF1 and PF2 containing 50% of PAMAM G3 was higher against human squamous carcinoma cells than human immortalized keratinocytes. The ability of the matrices to immobilize drugs was demonstrated in the example of perspective (Nimesulide, 8-Methoxypsolarene) or approved anticancer drugs (Doxorubicin-DOX, 5-Aminolevulinic acid). Release into the culture medium and penetration of DOX into the tested SCC-15 and HaCaT cells were also proved. The results show that further modification of the obtained matrices may lead to their use as drug delivery systems, e.g., for anticancer therapy.

Polyamidoamine dendrimer-modified polyvinylidene fluoride microporous membranes for protein separation

The separation efficiency of pressure-driven filtration membranes is primarily dictated by the membrane pore size. Membranes with larger pores typically demonstrate high flux but low or zero rejection when it comes to separating small molecules. In protein separation, ultrafiltration (UF) membranes with pore sizes smaller than the molecular dimensions of target proteins are commonly used for size rejection. Taking inspiration from the separation mechanism of nanofiltration (NF) membranes, we hypothesize that introducing charged groups into membranes of appropriate pore sizes could significantly enhance the electrical interaction between membrane charges and protein charges. This enhancement, occurring at the nanoscale distance when protein molecules approach or pass through charged nanoscale membrane channels, may enable the rejection of proteins substantially smaller than the pore size. Using membranes with relatively large pore sizes could lead to an increase in flux. To test this hypothesis, we conducted experiments involving the modification of polyvinylidene fluoride (PVDF) membranes with suitable pore sizes, using polyamidoamine (PAMAM) dendrimers to introduce negative charges to the membranes. The performance of the PVDF membranes and the modified membranes were investigated in the separation of whey proteins. To evaluate the contribution of steric and electrical hindrance to the solute separation, filtration experiments were performed using polyethylene oxide (PEO) and polyacrylic acid (PAA). The membranes were characterized using techniques such as attenuated total reflectance-Fourier transform infrared (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The results indicate that the modification enhances the rejection efficiency of whey proteins. The whey protein rejection and permeate flux for PVDF membranes were 58.9% and 15.3 LMH, respectively. Following alkaline treatment or PAMAM-G3.5 dendrimer modification, the whey protein rejection increased to 97.3% and 98.8%, respectively. However, alkaline treatment and PAMAM-G3.5 dendrimer modification resulted in a reduction of permeate flux to 5.6 LMH and 2.3 LMH, respectively. This suggests that increasing membrane charge effectively enhances the separation ability of filtration membranes in charged macromolecule separation.

Unilateral Administration of Surface-Modified G1 and G4 PAMAM Dendrimers in Healthy Mice to Assess Dendrimer Migration in the Brain.

Polyamidoamine (PAMAM) dendrimers are nanoparticles that have a wide scope in the field of biomedicine. Previous evidence shows that the generation 4 (G4) dendrimers with a 100% amine surface (G4-NH2) are highly toxic to cells in vitro and in vivo due to their positively charged amine groups. To reduce the toxicity, we modified the surface of the dendrimers to have more neutral functional groups, with 10% of the surface covered with -NH2 and 90% of the surface covered with hydroxyl groups (-OH; G4-90/10). Our previous in vitro data show that these modified dendrimers are taken up by cells, neurons, and different types of stem cells in vitro and neurons and glial cells in vivo. The toxicity assay shows that these modified dendrimers are less toxic compared with G4-NH2 dendrimers. Moreover, prolonged dendrimer exposure (G1-90/10 and G4-90/10), up to 3 weeks following unilateral intrastriatal injections into the striatum of mice, showed that dendrimers have the tendency to migrate within the brain via corpus callosum at different rates depending on their size. We also found that there is a difference in migration between the G1 and G4 dendrimers based on their size differences. The G4 dendrimers migrate in the anterior and posterior directions as well as more laterally from the site of injection in the striatum compared to the G1 dendrimers. Moreover, the G4 dendrimers have unique projections from the site of injection to the cortical areas.

Evaluation of Surface Topography and Biomimetic Remineralization Capacity of Dendrimers in Comparison With Calcium Silicate Cement: An In Vitro Study.

Biodentine, a calcium silicate-based material, is known for its biocompatibility and ability to promote dentin regeneration. With their unique branching structure, polyamidoamine (PAMAM) dendrimers have shown promise in facilitating biomimetic remineralization processes. This study investigates the synergistic effects of combining PAMAM with Biodentine on root dentin remineralization, aiming to develop a novel bioactive compound that offers superior protective and regenerative properties. The following predictions were made: (1) In a cyclic artificial saliva/acid regimen, among the test groups, the combination of Biodentine and PAMAM would cause the most root dentin remineralization (2). Biodentine alone would increase Ca and P concentrations, neutralize acid, and promote root dentin remineralization (3). PAMAM, on the other hand, can remineralize the demineralized root dentin. Minimal mineral regeneration was accomplished in demineralized root dentin when treated with Biodentine or PAMAM alone. Root dentin remineralization was most pronounced when Biodentine and PAMAM were used together, and the hardness of demineralized root dentin was raised to an equivalent level to that of healthy root dentin. The study demonstrated the exceptional ability of PAMAM + Biodentine to promote root dentin remineralization. In an acid-challenging environment, PAMAM + Biodentine promoted full and efficient root dentin remineralization. Restorations made using innovative PAMAM + Biodentine technology show promise in remineralizing and protecting tooth structures.

Selective Cellular Uptake and Druggability Efficacy through Functionalized Chitosan-Conjugated Polyamidoamine (PAMAM) Dendrimers.

Nanotechnology has ushered in significant advancements in drug design, revolutionizing the prevention, diagnosis, and treatment of various diseases. The strategic utilization of nanotechnology to enhance drug loading, delivery, and release has garnered increasing attention, leveraging the enhanced physical and chemical properties offered by these systems. Polyamidoamine (PAMAM) dendrimers have been pivotal in drug delivery, yet there is room for further enhancement. In this study, we conjugated PAMAM dendrimers with chitosan (CS) to augment cellular internalization in tumor cells. Specifically, doxorubicin (DOX) was initially loaded into PAMAM dendrimers to form DOX-loaded PAMAM (DOX@PAMAM) complexes via intermolecular forces. Subsequently, CS was linked onto the DOX-loaded PAMAM dendrimers to yield CS-conjugated PAMAM loaded with DOX (DOX@CS@PAMAM) through glutaraldehyde crosslinking via the Schiff base reaction. The resultant DOX@CS@PAMAM complexes were comprehensively characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Notably, while the drug release profile of DOX@CS@PAMAM in acidic environments was inferior to that of DOX@PAMAM, DOX@CS@PAMAM demonstrated effective acid-responsive drug release, with a cumulative release of 70% within 25 h attributed to the imine linkage. Most importantly, DOX@CS@PAMAM exhibited significant selective cellular internalization rates and antitumor efficacy compared to DOX@PAMAM, as validated through cell viability assays, fluorescence imaging, and flow cytometry analysis. In summary, DOX@CS@PAMAM demonstrated superior antitumor effects compared to unconjugated PAMAM dendrimers, thereby broadening the scope of dendrimer-based nanomedicines with enhanced therapeutic efficacy and promising applications in cancer therapy.

Engineering polyvinylidene fluoride membranes using charge tunable dendrimer polyamidoamine to enable microporous membranes for protein separation

Dendrimers are structurally precise molecules, whose peripheral layer provides ample sites for anchoring functional groups of different charges and charge densities. This characteristic renders them capability of providing numerous target functional groups on the surface of filtration membranes when modified by dendrimers. Consequently, there has been a growing interest in dendrimer-modified membranes. In this study, we investigated the engineering of polyvinylidene fluoride (PVDF) membranes using polyamidoamine (PAMAM) dendrimers anchoring different functional groups to tune the charges and charge density of membranes to enable microporous membranes for separation of charged macromolecules. PVDF membranes were functionalized by grafting PAMAM-G3.0 (generation 3) dendrimers with amine groups onto their surfaces and internal surfaces of membrane pores. Subsequently, the peripheral functional groups of dendrimers on the membranes were replaced by carboxyl groups, quaternary ammonium groups, or sulfonic acid groups for charges of different nature and densities. Surface chemical properties, electrical properties, and morphology were characterized using various techniques, including attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and surface zeta potential measurement. The filtration performance of both PVDF and modified membranes was evaluated using polyethylene oxide (PEO), polyacrylic acid (PAA), and whey protein filtration. Among the modified membranes, the G3PA membranes, with carboxyl functional groups, exhibited the most effective whey protein separation performance. The whey protein rejection and permeate flux of the G3PA membranes were 79 % and 30.3 LMH, respectively. As a comparison, the whey protein rejection and permeate flux of the pristine PVDF membranes were 58.9 % and 15.3 LMH, respectively.

Therapeutic Effects of PEG-Modified Polyamide Amine Dendrimer for Cell Free DNA Adsorption in Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJ OA) is characterized by the degeneration of cartilage and subchondral bone. In this study, we observed a significant increase in cell-free DNA (cfDNA) levels during the progression of TMJ OA. Bioinformatics analysis identified TLR9 as a pivotal molecule in TMJ OA pathogenesis. The polyamidoamine (PAMAM) dendrimer characterized by a well-structured, highly branched, and reactive nature, exhibits robust binding and clearance capabilities for cfDNA. However, the abundant amino groups on the surface of PAMAM lead to its inherent toxicity. To mitigate this, PEG-5000 was conjugated to the surface of PAMAM dendrimers, enhancing safety. Our results indicate that PEG-PAMAM effectively inhibits the upregulation of the TLR9 protein in TMJ OA, significantly suppressing the activation of the p-IκBα/p-NF-κB signaling pathway and subsequently decreasing chondrocyte inflammation and apoptosis, as evidenced by both in vivo and in vitro experiments. We conclude that PEG-PAMAM is a safe and effective material for in vivo applications, offering a promising therapeutic strategy for TMJ OA by targeting cfDNA clearance.