PAMAM Research Articles

Carbonylative Cyclization of 2-Iodofluorobenzenes and 2-Aminophenols with Recyclable Palladium-Complexed Dendrimers on SBA-15: One-Pot Synthesis of Dibenzoxazepinones.

A novel, efficient, and practical route to dibenzoxazepinones has been developed through a one-pot heterogeneous palladium-catalyzed aminocarbonylation/aromatic nucleophilic substitution (SNAr) sequence starting from readily available 2-iodofluorobenzenes and 2-aminophenols. The carbonylative cyclization reaction proceeds smoothly in dimethyl sulfoxide (DMSO) at 120 °C with 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as the base by using a polyamidoamine (PAMAM)-dendronized SBA-15-supported bidentate phosphine-palladium complex [G(1)-2P-Pd(OAc)2-SBA-15] as the catalyst under 10 bar of CO, yielding a wide variety of dibenzo[b,e][1,4]oxazepin-11(5H)-one derivatives in good to excellent yields. Moreover, this new heterogenized dendritic palladium catalyst has competitive advantages in that it can be facilely recovered by simple filtration in air and recycled more than eight times without any significant loss of activity. The broad substrate scope, high functional group tolerance, and excellent palladium catalyst recyclability of the reaction make this approach a general, efficient, and economical method for the construction of valuable dibenzoxazepinone derivatives.

PAMAM-Based Polymeric Immunogenic Cell Death Inducer To Potentiate Cancer Immunotherapy.

Immunogenic cell death (ICD) has been widely employed to potentiate cancer immunotherapy due to its capability to activate the anticancer immune response. Although various ICD inducers have been described, the development of synthetic materials with intrinsic ICD-inducing competency has rarely been reported. Herein, we identify a derivative of the fourth generation polyamidoamine (PAMAM) modified with multiple seven-membered heterocyclic rings, G4P-C7A, as a robust ICD inducer. G4P-C7A evokes characteristic release of damage-associated molecular patterns in tumor cells and induces efficient dendritic cell maturation. Mechanistic studies suggest that G4P-C7A can selectively accumulate in the endoplasmic reticulum and mitochondria to generate reactive oxygen species. G4P-C7A-treated tumor cells can work as potent vaccines to protect against secondary tumor implantation. Either local or systemic injection of G4P-C7A alone can effectively inhibit tumor growth by eliciting robust antitumor immune response. The combination of G4P-C7A with immunotherapeutic antibodies such as anti-PD1 (aPD-1) and anti-CD47 (aCD47) further potentiates the antitumor effect in either CT26 or 4T1 tumor model. This study offers a simple but effective strategy to induce ICD to boost cancer immunotherapy.

A size-switchable nanocluster remodels the immunosuppressive microenvironment of tumor and tumor-draining lymph nodes for improved cancer immunotherapy

Remodeling the immunosuppressive tumor microenvironment (TME) by immunomodulators has been well studied in the past years. However, strategies that enable concurrent modulation of both the immunosuppressive TME and tumor-draining lymph nodes (TDLNs) are still in the infancy. Here, we report a pH-sensitive size-switchable nanocluster, SPN-R848, to achieve simultaneous accumulation in tumor and TDLNs for immune activation. SPN-R848 with original size around 150 nm was formed by self-assembly of resiquimod (R848)-conjugated polyamidoamine (PAMAM) derivative, which could disintegrate into its small constituents (～ 8 nm) upon exposure to tumor acidity. The size reduction not only enhanced their accumulation and perfusion in the primary tumor, but promoted their transport and distribution in TDLNs. Accordingly, SPN-R848 remarkably remodeled the immunosuppressive TME by polarizing M2 to M1 macrophages and activated dendritic cells (DCs) in TDLNs, which synergistically facilitated the production and stimulation of cytotoxic T cells, and inhibited tumor growth in breast cancer and melanoma mouse models. Our study suggests that co-activation of immune microenvironments in both tumor and TDLNs may represent a promising direction to elicit strong antitumor immunity.

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.

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.

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.

Effects of dehydration time on performances of polyamidoamine-epichlorohydrin resin and its modified soybean-based adhesive

Soybean-based adhesive has been commercialized in the wood industry owing to its several advantages, such as no formaldehyde, good bonding properties, and renewability. However, the large-scale application of soybean-based adhesive is greatly limited by its significantly higher cost than urea-formaldehyde resin. Thus, in this study, a cost-effective polyamidoamine-epichlorohydrin (PAE) resin with improved crosslinking efficiency to soybean meal was prepared from branched polyamidoamine (PAA) with reduced dehydration time at high temperatures. Test results from GPC, FTIR and NMR analyses showed that traditional PAA synthesis involving 3-h dehydration time at 180 °C resulted in over-branching of PAA resin and poor crosslinking efficiency of PAE resin and decreased water resistance of obtained soybean-based adhesive. PAA resin synthesized at appropriate dehydration time (1 h) remained sufficient secondary amine groups for being grafted by epichlorohydrin to form effective PAE resin with more azetidinium groups. As a result, the water resistance of soybean-based adhesive crosslinked by the optimal PAE-1 resin prepared from 1 h-dehydrated PAA-1 significantly improved by 42.9 % compared with that of soybean-based adhesive crosslinked by traditional PAE resin, attributing to forming denser and stronger crosslinking networks after thermally cured. Consequently, this optimal PAE-1 could reduce the cost of soybean-based adhesive due to decreasing 16.7 wt% of PAE dosage without compromising bonding property and the energy consumption of PAA/PAE synthesis. Therefore, an appropriate decrease in the dehydration time of PAA resin at a high temperature provides an effective, economical, and energy-saving strategy to improve the bonding property of soybean-based adhesives.

Mannosylated PAMAM G2 dendrimers mediated rate programmed delivery of efavirenz target HIV viral latency at reservoirs

In this current research, we conceptualized a novel nanotechnology-enabled synthesis approach of targeting HIV-harboring tissues via second-generation (G2) polyamidoamine (PAMAM) mannosylated (MPG2) dendrimers for programmed delivery of anti-HIV drugs efavirenz (EFV) and ritonavir (RTV). Briefly, here mannose served purpose of ligand in this EFV and RTV-loaded PAMAM G2 dendrimers, synthesized by divergent techniques, denoted as MPG2ER. The developed nanocarriers were characterized by different analytical tools FTIR, NMR, zeta potential, particle size, and surface morphology. The results of confocal microscopy showed substantial alterations in the morphology of H9 cells, favored by relatively higher drug uptake through the MPG2ER. Interestingly, the drug uptake study and cytotoxicity assay of MPG2ER demonstrated that it showed no significant toxicity up to 12.5 µM. A typical flow cytometry histogram also revealed that MPG2ER efficiently internalized both drugs, with an increase in drug uptake of up to 81.2 %. It also enhanced the plasma pharmacokinetics of EFV, with Cmax7.68 μg/ml, AUC of 149.19 (μg/ml) * hr, and MRT of 26.87 hrs. Subsequently, tissue pharmacokinetics further evidence that MPG2ER accumulated more in distant Human immunodeficiency virus (HIV) reservoir tissues, such as the lymph nodes and spleen, but without exhibiting significant toxicity. Abovementioned compelling evidences strongly favored translational roles of MPG2 as a potential therapeutic strategy in the clinical eradication of HIV from viral reservoir tissue.

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.

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.

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.

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.

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.

Synthesis and characterization of ZnO quantum dot-functionalized mesoporous nanocarriers for controlled drug delivery

In this study, ZnO quantum dots (ZnO@QDs) were synthesized and functionalized with 2nd generation poly amido amine (2GPD) using 3-amino-propyl tri-methoxy silane as the initiator core, facilitated by tetramethylammonium hydroxide (TMAH) to enhance stability against oleate coating. Concurrently, a mesoporous substrate with a unique morphology was developed as a drug reservoir for doxorubicin loading. ZnO quantum dots displayed photoluminescence radiation, with dimensions ranging from 5 to 7 nm and exhibiting spherical morphology. The cubic structure of the synthesized mesoporous nanocatalysts was also confirmed. Brunauer-Emmett-Teller analysis indicated a multidimensional porous structure of the nanocarriers, while zeta potential analysis showed a stable system (approximately −9.6 mV). Fourier transform infrared spectroscopy, X-ray diffraction, and energy dispersive spectroscopy corroborated these findings. Drug release studies demonstrated sustained release under acidic conditions (pH 5.5), with an efficiency of approximately 94 %. These results highlight the potential applications of this nanosystem for controlled drug delivery, underscoring its practical implications in the field of nanotechnology.

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.

Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy.

Glioma is the most common primary intracranial tumor, which is formed by the malignant transformation of glial cells in the brain and spinal cord. It has the characteristics of high incidence, high recurrence rate, high mortality and low cure rate. The treatments for glioma include surgical removal, chemotherapy and radiotherapy. Due to the obstruction of the biological barrier of brain tissue, it is difficult to achieve the desired therapeutic effects. To address the limitations imposed by the brain's natural barriers and enhance the treatment efficacy, researchers have effectively used brain-targeted drug delivery systems (DDSs) in glioma therapy. Polyamidoamine (PAMAM) dendrimers, as branched macromolecular architectures, represent promising candidates for studies in glioma therapy. This review focuses on PAMAM-based DDSs in the treatment of glioma, highlighting their physicochemical characteristics, structural properties as well as an overview of the toxicity and safety profiles.