Dendrimer Complexes Research Articles

Dendritic Pyridine-Imine Copper Complexes as Metallo-Drugs.

Since the discovery of cisplatin in the 1960s, the search for metallo-drugs that are more efficient than platinum complexes with negligible side effects has attracted much interest. Among the other metals that have been examined for potential applications as anticancer agents is copper. The interest in copper was recently boosted by the discovery of cuproptosis, a recently evidenced form of cell death mediated by copper. However, copper is also known to induce the proliferation of cancer cells. In view of these contradictory results, there is a need to find the most suitable copper chelators, among which Schiff-based derivatives offer a wide range of possibilities. Gathering several metal complexes in a single, larger entity may provide enhanced properties. Among the nanometric objects suitable for such purpose are dendrimers, precisely engineered hyperbranched macromolecules, which are outstanding candidates for improving therapy and diagnosis. In this review article, we present an overview of the use of a particular Schiff base, namely pyridine-imine, linked to the surface of dendrimers, suitable for complexing copper, and the use of such dendrimer complexes in biology, in particular against cancers.

Characterization of a Novel TiF4 Inclusion Complex and in vitro Evaluation of Its Effect on Inhibiting Enamel Demineralization

Introduction: Titanium tetrafluoride (TiF4) is an anticariogenic agent with high remineralizing potential. However, the acidic pH of TiF4 solution can limit its clinical application. The present study aimed to prepare and characterize a new TiF4-dendrimer inclusion complex and evaluate its ability to inhibit enamel demineralization under pH cycling conditions. Methods: PEG-citrate dendrimer and TiF4-dendrimer inclusion complex were synthesized and their molecular structures were evaluated using Fourier-transform Infrared Spectroscopy (FTIR), Hydrogen Nuclear Magnetic Resonance (HNMR), and Liquid Chromatography-Mass Spectrometry (LC-MS) tests. Forty-eight enamel samples were prepared and randomly divided into four groups: distilled water (negative control), TiF4 solution (T), dendrimer solution (D), and TiF4-dendrimer solution (TD). The microhardness of the samples was measured initially. Next, the samples underwent pH cycling, were exposed to the solutions, the microhardness was measured again, and microhardness loss was calculated. EDX analysis was performed on the surface and cross-sectional segments of the samples. Results: The microhardness loss was significantly higher in control (−65.1 ± 6.0) compared to other groups. No significant difference was observed between T (−47.9 ± 5.6) and D (−41.7 ± 12.0) and also D and TD (−40.5 ± 9.4) in this regard. Microhardness loss was significantly higher in T compared to TD group. The TD samples showed similar fluoride and titanium content in both surface and subsurface regions, while the T group had higher concentrations in the surface region. Moreover, the TD solution had a higher pH of 3.4 compared to the T solution’s pH of 1.1. Conclusion: No significant difference was observed between the efficacy of TiF4-dendrimer and TiF4 solution in inhibiting demineralization while TiF4-dendrimer solution had the added advantage of having a higher pH.

DENDRIMERS IN NOVEL DRUG DELIVERY SYSTEM: AN UPDATED REVIEW

Nanoscale molecules known as dendrimers possess clearly defined, uniform, and monodisperse structures. They’re composed of a symmetrical core with an outside and interior shell. Due to their multiple beneficial features, dendrimers are an excellent choice in the medical field; this page compiles all of their different uses. Many different kinds of poly (propylene imine) and poly (amidoamine) dendrimers integrated with imatinib, sunitinib, cisplatin, melphalan, doxorubicin, paclitaxel, and methotrexate have shown advantages over the drug molecule alone. Dendrimers have undergone extensive research for their potential as anti-cancer agents. The mainstay of the inflammatory medicine was dendrimer complexes of indomethacin, piroxicam, ketoprofen ibuprofen, and diflunisal. Given the circumstances, the growth of bacterial strains resilient to antibiotics, fluoroquinolone, macrolide, beta-lactamine, and aminoglycoside dendrimer complexes have shown positive outcomes. In relation to treatment with antiviral drugs, There has been a study to create dendrimers being conjugated with tenofovir, maraviroc, zidovudine, oseltamivir, and other antivirals. Additionally, dendrimers have successfully allured much interest in cardiovascular medicine. Large, multi-component macromolecules constitute dendrimers. The present review enlists all kinds of related scientific and valuable aspects of dendrimers to help the researcher working with dendrimers.

A Molecular Dynamics Simulation of Complexes of Fullerenes and Lysine-Based Peptide Dendrimers with and without Glycine Spacers.

The development of new nanocontainers for hydrophobic drugs is one of the most important tasks of drug delivery. Dendrimers with hydrophobic interiors and soluble terminal groups have already been used as drug carriers. However, the most convenient candidates for this purpose are peptide dendrimers since their interiors could be modified by hydrophobic amino acid residues with a greater affinity for the transported molecules. The goal of this work is to perform the first molecular dynamics study of the complex formation of fullerenes C60 and C70 with Lys-2Gly, Lys G2, and Lys G3 peptide dendrimers in water. We carried out such simulations for six different systems and demonstrated that both fullerenes penetrate all these dendrimers and form stable complexes with them. The density and hydrophobicity inside the complex are greater than in dendrimers without fullerene, especially for complexes with Lys-2Gly dendrimers. It makes the internal regions of complexes less accessible to water and counterions and increases electrostatic and zeta potential compared to single dendrimers. The results for complexes based on Lys G2 and Lys G3 dendrimers are similar but less pronounced. Thus, all considered peptide dendrimers and especially the Lys-2Gly dendrimer could be used as nanocontainers for the delivery of fullerenes.

Fucoidan and dendrimer-based nanocapsule exhibiting effectiveness in methotrexate controlled delivery towards rheumatoid arthritis treatment

In recent years, nanomaterials have been intensively studied and applied in various fields, including pharmaceutical applications. This platform can act as a carrier for anticancer drugs or for insoluble bioactive compounds. To increase the stability and prolong the effect of anticancer drugs, we have incorporated a sulfated polysaccharide fucoidan (Fu) into PAMAM dendrimer G3.0 to form a G3.0-Fu complex. Then, a nano-sized encapsulated anticancer drug, methotrexate (MTX), was successfully embedded in the synthesised dendrimer complex namely G3.0-Fu/MTX. Newly synthesised G3.0-Fu/MTX was characterised by transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential measurement.Additionally, the loading efficiency of MTX was assessed via UV spectroscopy. Our findings revealed that upon combining with Fu, the G3.0 nanoparticle size increased from 4.3 ± 1.1 nm to 56 ± 6 nm. The changes in zeta potential aligned with drug entrapment efficiency and the results from TEM and DLS. The drug release activity of G3.0-Fu/MTX was increased compared to free MTX after 24 h. G3.0-Fu also showed high cytocompatibility in fibroblast cells. Taken together, the G3.0-Fu could be used to increase the encapsulation of several kinds of hydrophobic drugs and G3.0-Fu/MTX could be further studied in rheumatoid arthritis treatment.

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.

Radiolabeled Dendrimer Coated Nanoparticles for Radionuclide Imaging and Therapy: A Systematic Review

Dendrimers are nanoscale-size polymers with a globular structure. They are composed of an internal core and branching dendrons with surface active groups which can be functionalized for medical applications. Different complexes have been developed for imaging and therapeutic purposes. This systematic review aims to summarize the development of newer dendrimers for oncological applications in nuclear medicine. An online literature search was conducted on Pubmed, Scopus, Medline, Cochrane Library, and Web Of Science databases selecting published studies from January 1999 to December 2022. The accepted studies considered the synthesis of dendrimer complexes for oncological nuclear medicine imaging and therapy. 111 articles were identified; 69 articles were excluded because they did not satisfy the selection criteria. Thus, nine duplicate records were removed. The remaining 33 articles were included and selected for quality assessment. Nanomedicine has led researchers to create novel nanocarriers with high affinity for the target. Dendrimers represent feasible imaging probes and therapeutic agents since, through the functionalization of external chemical groups and thanks to the possibility to carry pharmaceuticals, it can be possible to exploit different therapeutic strategies and develop a useful weapon for oncological treatments.

Complexes of Cationic Pyridylphenylene Dendrimers with Anionic Liposomes: The Role of Dendrimer Composition in Membrane Structural Changes.

In the last decades, dendrimers have received attention in biomedicine that requires detailed study on the mechanism of their interaction with cell membranes. In this article, we report on the role of dendrimer structure in their interaction with liposomes. Here, the interactions between cationic pyridylphenylene dendrimers of the first, second, and third generations with mixed or completely charged pyridyl periphery (D16+, D215+, D229+, and D350+) with cholesterol-containing (CL/Chol/DOPC) anionic liposomes were investigated by microelectrophoresis, dynamic light scattering, fluorescence spectroscopy, and conductometry. It was found that the architecture of the dendrimer, namely the generation, the amount of charged pyridynium groups, the hydrophobic phenylene units, and the rigidity of the spatial structure, determined the special features of the dendrimer-liposome interactions. The binding of D350+ and D229+ with almost fully charged peripheries to liposomes was due to electrostatic forces: the dendrimer molecules could be removed from the liposomal surfaces by NaCl addition. D350+ and D229+ did not display a disruptive effect toward membranes, did not penetrate into the hydrophobic lipid bilayer, and were able to migrate between liposomes. For D215+, a dendrimer with a mixed periphery, hydrophobic interactions of phenylene units with the hydrocarbon tails of lipids were observed, along with electrostatic complexation with liposomes. As a result, defects were formed in the bilayer, which led to irreversible interactions with lipid membranes wherein there was no migration of D215+ between liposomes. A first-generation dendrimer, D16+, which was characterized by small size, a high degree of hydrophobicity, and a rigid structure, when interacting with liposomes caused significant destruction of liposomal membranes. Evidently, this interaction was irreversible: the addition of salt did not lead to the dissociation of the complex.

The importance of pH for the formation of stable and active quercetin–polyamidoamine dendrimer complex

AbstractThe purpose of this study was to investigate the effect of pH on the complexation of quercetin and polyamidoamaine (PAMAM) dendrimers, which can exert antioxidant activity in aqueous solution. The therapeutic use of quercetin has been limited due to its low water solubility and bioavailability. In this study, quercetin was complexed with generation 4 PAMAM (G4) in different buffers at pH 4–9, with pH 6 showing the best results in terms of solubility and stability. The solubility of quercetin in 0.1 M phosphate buffer at pH 6.0 containing 1% G4 was over 1 mg/ml. The antioxidant and neuroprotective activities of water‐soluble G4–quercetin complex (G4‐Q) were comparable to those of free quercetin dissolved in methanol. In conclusion, this study indicates that the complexation of quercetin with PAMAM dendrimers was optimized at pH 6 and the complex exhibits good water solubility, strong antioxidant activity, and neuroprotective activity.

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.

Multifunctional Therapeutic Cyclodextrin-Appended Dendrimer Complex for Treatment of Systemic and Localized Amyloidosis.

Amyloidosis pathologically proceeds via production of amyloidogenic proteins by organs, formation of protein aggregates through structural changes, and their deposition on tissues. A growing body of evidence demonstrates that amyloidosis generally develops through three critical pathological steps: (1) production of amyloid precursor proteins, (2) amyloid formation, and (3) amyloid deposition. However, no clinically effective therapy that is capable of targeting each pathological step of amyloidosis independently is currently available. Here, we combined therapeutic effects and developed a short hairpin RNA expression vector (shRNA) complex with a cyclodextrin-appended cationic dendrimer (CDE) as a novel multitarget therapeutic drug that is capable of simultaneously suppressing these three steps. We evaluated its therapeutic effects on systemic transthyretin (ATTR) amyloidosis and Alzheimer's disease (AD) as localized amyloidosis, by targeting TTR and amyloid β, respectively. CDE/shRNA exhibited RNAi effects to suppress amyloid protein production and also achieved both inhibition of amyloid formation and disruption of existing amyloid fibrils. The multitarget therapeutic effects of CDE/shRNA were confirmed by evaluating TTR deposition reduction in early- and late-onset human ATTR amyloidosis model rats and amyloid β deposition reduction in AppNL-G-F/NL-G-F AD model mice. Thus, the CDE/shRNA complex exhibits multifunctional therapeutic efficacy and may reveal novel strategies for establishing curative treatments for both systemic and localized amyloidosis.

Equable Fine-tuning Techniques of Bimetallic Co-complexation in Dendrimer for Cluster Synthesis Covering a Wide Range of Composition

Precise preparation of multinuclear bimetallic dendrimer complexes with finely-controlled compositions was investigated for template synthesis of alloy clusters by using platinum and tin. An ordered complexation behavior of metal salts in the dendrimer with imine units enabled bimetallic co-accumulations in a dendrimer template while combinations of metal salts with various acidity achieved the formation of 27 patterns of complexes. This fine-tuning technique of compositions in the dendrimer complexes leads to precise synthesis of alloy clusters covering wider range of composition.

49P Antitumor effects of cationic dendritic molecules and their complexes with microRNA in glioblastoma stem-like cells

An important way for anti-tumor drug development is using of molecular targets involved in the regulatory pathways during tumorogenesis. As it was found microRNAs (miRs) are active players in this processes. Manipulations with miR-34a and onco-miR-21 demonstrated their effectiveness as antitumor intervention in glioblastoma (GBM), so stable and efficient nanocarriers should be found. One of the promising approach is using of dendrimers – highly symmetrical hyperbranched polymers. The aim of our study was evaluation of effects of treatment by complexes of dendrimers with miRs on human glioblastoma stem-like cells (GSCs).

Dendriplex-Impregnated Hydrogels With Programmed Release Rate.

Hydrogels are biocompatible matrices for local delivery of nucleic acids; however, functional dopants are required to provide efficient delivery into cells. In particular, dendrimers, known as robust nucleic acid carriers, can be used as dopants. Herein, we report the first example of impregnating neutral hydrogels with siRNA–dendrimer complexes. The surface chemistry of dendrimers allows adjusting the release rate of siRNA-containing complexes. This methodology can bring new materials for biomedical applications.

MD Simulation of AEDG Peptide Complexes with New K2R Dendrimer and Dendrigraft

Biocompatible peptide dendrimers and dendrigrafts have useful properties for application in biomedicine. In previous papers the computational approach for study lysine dendrimers and dendrigrafts as well as their complexes with various medical peptides was used. In this paper the comparison of complex formation between molecules of therapeutic AEDG tetrapeptide and novel K2R peptide dendrimer or DG2 dendrigraft of near the same size and charge was fulfilled. The systems consisting of 16 therapeutic AEDG tetrapeptide molecules and one dendrimer or one dendrigraft were studied by molecular dynamics simulation. Full atomic models of these molecules in water with explicit counterions were used for this goal. First of all, the process of complex formation was studied. It was obtained that peptide molecules were attracted by both branched molecules and were quickly adsorbed by them. Times of complexes formation as well as size, anisotropy and structure of each complex were calculated. It was demonstrated that both K2R dendrimer and DG2 dendrigraft are effective for complexation of these peptide molecules but new dendrimer complex is more stable than dendrigraft complex because it has almost twice more hydrogen bonds with peptide molecules and 33% more ion pairs with their charged groups.

Cotton Fabric Modified with a PAMAM Dendrimer with Encapsulated Copper Nanoparticles: Antimicrobial Activity.

A new methodology for modifying textile materials with dendrimers containing nanoparticles was developed. This involved a combination of eosin Y and N-methyldiethanolamine (MDEA) for reducing the copper ions in the dendrimer complex by enabling a photochemical reaction under visible light and ambient conditions. The conversion of copper ions into nanoparticles was monitored using scanning electron microscopy (SEM) and by performing colorimetric, fluorescence, and electron paramagnetic resonance (EPR) studies. Regardless of the concentration of the photoinitiator eosin Y, it discolored completely upon illumination. Three types of cotton fabrics were compared as antimicrobial materials against Bacillus cereus. One of the fabrics was dyed with a first-generation PAMAM dendrimer which had been functionalized with eight 1,8-naphthalimide fluorophores. Another fabric was dyed with a dendrimer–copper complex, and the third was treated by conversion of the complex into copper nanoparticles encapsulated into the dendrimer. An enhancement in the antimicrobial activity of the textiles was achieved at higher dendrimer concentrations, under illumination with visible light. The fabric modified with the copper nanoparticles encapsulated inside the dendrimer exhibited the best antibacterial activity because it had two photosensitizers (PS), as both 1,8-naphthalimide fluorophores and copper nanoparticles were contained in the dendrimer molecules. The presence of oxygen and suitable illumination activated the photosensitizers to generate the reactive oxygen species (singlet oxygen (1O2) and other oxygenated products, e.g., anion radicals, hydroxyl radicals, and hydrogen peroxide) responsible for destroying the bacteria.

Unique Functions and Applications of Rigid Dendrimers Featuring Radial Aromatic Chains.

Dendrimers, which are highly branched polymers and regarded as huge single molecules, are interesting substances from the aspect of not only polymer chemistry but also molecular chemistry. Various applications in materials science and life science have been investigated by taking advantage of the radially layered structures and intramolecular nanospaces of dendrimers. Most dendrimers have flexible structures that originate from their organic chains which contain many sp3-type atoms, while relatively rigid dendrimers composed only of sp2-type atoms have rarely been reported. It has been recently clarified that such rigid dendrimers exhibit a specific aromatic property not found in other materials. Dendritic phenylazomethines (DPAs), as one of the rigid dendrimers, have only sp2-type C and N atoms and possess a radially branched π-conjugation system in their own macromolecular chains. Such geometric and electronic structures heighten the electron density at the core of the dendrimer and induce an intramolecular potential gradient, which affords unique reactivities that lead to extraordinary functions. This unique property of the rigid dendrimers can be regarded as a new atypical electronic state based on radial aromatic chains not found in conventional aromatic compounds containing spherical aromaticity, Möbius aromaticity, metal aromaticity, and conductive polymers. Therefore, this as-yet-unknown characteristic is expected to contribute to the further development of fundamental and materials chemistry.In this Account, we highlight the rigid DPA dendrimers and their peculiar atomically precise and selective assembly behaviors that originate from the radial aromatic chains. One of the most noteworthy attainments based on the radial aromatic chains is the precise synthesis of a multimetallic multinuclear complex of a dendrimer containing a total of 13 elements. Next, we describe the electrochemical and catalytic functionalization of such multinuclear dendrimer complexes and the construction of supramolecular nanoarchitectures by the polymerization of DPAs. These complexes exhibit encapsulation-release switching of guests and additive-free catalytic ability similar to proteins and enzymes. Such selective and accurate control of the intramolecular assembly of guests and the intermolecular arrangement of hosts realized by the radial aromatic chains of dendrimers will enable supramolecular chemistry and biochemistry to be linked from a new aspect. In addition, the multimetallic multinuclear complexes of dendrimers afford a novel approach to precisely synthesize sub-nanoparticles with ultrasmall particle sizes (1 nm) that have been technically difficult to obtain by conventional nanotechnology. We discuss the method for the synthesis of these sub-nanoparticles with well-controlled atomicity and composition using DPA complexes as a template and recent advances to reveal their specific physical and chemical properties. These results suggest that the unique electronic states induced in such radial aromatics could play an important role in the development of next-generation chemistry.

Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs.

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

Metal atom-guided conformational analysis of single polynuclear coordination molecules.

Microscopic observation of single molecules is a rapidly expanding field in chemistry and differs from conventional characterization techniques that require a large number of molecules. One of such form of single-molecule microscopy is high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), which is especially suitable for coordination compounds because of its atomic number-dependent contrast. However, to date, single-molecule observations using HAADF-STEM has limited to simple planar molecules. In the present study, we demonstrate a direct structural investigation of nonplanar dendronized polynuclear Ir complexes with subnanometer resolution using Ir as an atomic label. Decreasing the electron dose to the dendrimer complexes is critical for the single-molecule observation. A comparison with simulated STEM images of conformational isomers is performed to determine the most plausible conformation. Our results enlarge the potential of electron microscopic observation to realize structural analysis of coordination macromolecules, which has been impossible with conventional methods.

In-vitro evaluation of dendrimeric formulation of oxaliplatin

The aim of this study is, preparing various dendrimeric formulations of oxaliplatin and investigating their properties. First of all, the solubility enhancement capabilities of polyamidoamine (PAMAM) G3.5 and PAMAM G4.5 dendrimers were investigated. The results showed that oxaliplatin solubility mostly increasing linearly with dendrimer concentration. Additionally, the increase was more notable in PAMAM G4.5 dendrimers. Then, drug–dendrimer complexes were prepared in different mediums, since the medium used can affect the amount of drug-loaded to dendrimers. Prepared complexes were examined for loading capacity and loading efficiency. It was found that PAMAM G4.5 dendrimers can complex with 2- to 5-fold more oxaliplatin than PAMAM G3.5. Finally, oxaliplatin was modified to a platinum (IV) compound to prepare chemical drug–dendrimer conjugates. Ester bonds were established by Steglich esterification through the hydroxyl group of modified oxaliplatin and the carboxyl groups of the dendrimers. The formulations were characterized by UV, IR, NMR spectroscopy, and dynamic light scattering techniques. PAMAM G3.5 conjugate was further evaluated for the cytotoxicity test. The IC50 value of PAMAM G3.5 conjugate was found as 0.72 µM. For unmodified oxaliplatin, this value was 14.03 µM. As a result, a dendrimer-based drug delivery system that has been found promising for further improvement has been developed successfully.