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Sulfamethoxazole (SMZ) is a sulfonamide and used widely in the treatment of bacteriostatic and urinary tract infections with trimethoprim as an antibiotic. The problem with SMZ is its poor water solubility, therefore, low bioavailability in clinical applications. In this study, we synthesized new-generation Tris(2-aminoethyl)amine (TREN)-cored amine (NH 2 ), Tris(hydroxymethyl)aminomethane (TRIS), and carboxyl (COOH) terminated different generations T2-T4 poly(amidoamine) PAMAM dendrimers. Synthesized PAMAMs were characterized by 1 H NMR, 13 C NMR, ATR-FTIR, spectroscopic titrations, and evaluated as potential solubility enhancers and drug carriers of sulfonamides by taking SMZ as a model drug. The effect of concentration, generation, and surface groups of PAMAMs on the solubility of SMZ was also investigated. Results showed that the solubility of SMZ improved significantly with an increasing generation size (T2-T4) and PAMAM dendrimer concentration (0-2 mM). The role of PAMAMs in the solubility enhancement of SMZ was in the order of T4.NH 2  > T4.COOH > T3.NH 2  > T4.TRIS > T2.NH 2  > T3.COOH > T3.TRIS > T2.COOH > T2.TRIS, and in the ranges of 5- to 45-fold with maximum SMZ loading 7 to 61 mole/mole per PAMAM dendrimer molecule. In vitro release studies demonstrated that SMZ-PAMAM dendrimer complexes at the end of 2-h drug release (16-26%) was considerable slower than pure SMZ (38.8%).

This article investigates the aqueous solubility of the poorly soluble drug candesartan cilexetil (CC) in the presence of poly(amidoamine) (PAMAM) dendrimers. The effect of variables such as concentration, generation size (G2-G4), and surface groups (NH 2 , COOH and TRIS) of PAMAMs on the aqueous solubility of CC was studied. A two-factor factorial (3 × 3) ANOVA design was used to study the effect of generation size and surface functional group of the PAMAMs. The results showed that the aqueous solubility of CC in the presence of carboxyl and TRIS-terminated PAMAMs was higher than those of amine-terminated PAMAMs, and the effect of surface functional group of the PAMAMs on the aqueous solubility of CC was dependent on the generation size (p < 0.05). The sequence of the observed solubility fold enhancement due to PAMAMs was G4.COOH (8378)>G3.COOH (3456)>G4.TRIS (2362)>G2.COOH (1013)>G3.TRIS (749)>G2.TRIS (293)>G4.NH 2 (91)>G3.NH 2 (50)>G2.NH 2 (37). The CC-PAMAM dendrimer inclusion complexes were characterized by UV-Vis, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and differential thermal analysis (DTA) techniques. Regarding the results of these techniques, improvement in the solubility of CC is expected primarily through the intermolecular hydrogen bonding between the drug and internal tertiary and surface functional groups of the studied PAMAMs.

Starting from Ethylenediamine (EDA) or poly(ethylene glycol) tetra amine (4-arm-PEG) cores, two different peripheral methylester (-COOCH3) or amine (-NH2) PAMAM dendrimers have been synthesized. In the growth phase of dendrimers, two important building blocks, methyl acrylate for the half generation and EDA for the full generations, have been used. In order to improve the yield and decrease the time for the aminolysis step, a microwave-assisted technique was applied. Both of these dendrimers with different cores were grown up to 4.5 generations where surface modification, i.e. PEGylation, with 10% Poly(ethylene glycol) bis(amine) was performed. In order to increase the solubility of dendrimers, esteric surfaces were converted to carboxylic acid groups. Accordingly, the dendrimers were soluble in water or in water-methanol mixture which enabled their purification by liquid-phase polymer-based retention in each step. Finally, the resulting products that were characterized with (NMR and FTIR) spectroscopy were evaluated in vitro and in vivo. The analytical grade dendrimers were not cytotoxic to mouse fibroblasts and their biodistribution was mainly determined in the site of injection (peritoneum), liver and kidneys.

Glycosylated proteins modulate various important functions of organisms. To reveal the functions of glycoproteins, in‐depth characterization studies are necessary. Although mass spectrometry is a very efficient tool for glycoproteomic and glycomic studies, efficient sample preparation methods are required prior to analyses. In the study, poly(amidoamine) dendrimer‐coated magnetic nanoparticles were presented for the specific enrichment and fast purification of glycopeptides and glycans. The enrichment and purification performance of the developed method was evaluated both at the glycopeptide, and the glycan level using several standard glycoprotein digests and released glycan samples. The poly(amidoamine) dendrimer‐coated magnetic nanoparticles not only showed selective affinity (Immunoglobulin G/Bovine Serum Albumin, 1/10 by weight) to glycopeptides and released glycans but also good sensitivity (0.4 ng/µL for Immunoglobulin G) for glycoproteomic and glycomic applications. Thirty‐five glycopeptides of Immunoglobulin G were detected after enrichment with poly(amidoamine) dendrimer‐coated magnetic nanoparticles. In addition, 55 18O tagged deamidated glycopeptides belonging to human plasma glycoproteome were confirmed. Finally, fifty 2‐aminobenzoic acid, and 30 procainamide‐labelled human plasma N‐glycans released from human plasma glycoproteins were determined after purifications. The results indicate that the proposed enrichment and purification method using poly(amidoamine) dendrimer‐coated magnetic nanoparticles could be simply adjusted to sample preparation methods. [ABSTRACT FROM AUTHOR]

Abstract: This study reports the use of a new microwave assisted amidation method for the synthesis of Jeffamine cored poly (amidoamine) (PAMAM) dendrimers up to fourth generations. Reaction proceeding is monitored by attenuated total reflectance (ATR) without final purification. It was found that current method decreases the aminolysis time, and minimizes the excessive use of reagents and solvents. Synthesized dendrimers were purified by liquid-phase polymer-based retention (LPR) technique and characterized by 1H-NMR, 13C-NMR, EA, GPC and UV–VIS spectroscopy. [Copyright &y& Elsevier]

The objective of this study is to make comprehensive cytotoxicity evaluation and in vitro characterization of Jeffamine-cored polyamidoamine (PAMAM) dendrimers on L929 cell lines for oral drug delivery purposes. Ester-, amine- and carboxylic acid-terminated PAMAMs were investigated for their cytotoxicity on L929 cells at different generations and concentrations. Cationic surface charge caused highest cytotoxicity on L929 cells, while ester-terminated PAMAMs showed generation- and concentration-dependent toxicity. Anionic dendrimers were determined as the lowest cytotoxic group, and highest generation number presented lowest cellular toxicity. Encapsulation studies were performed with anionic PAMAMs at 2.5, 3.5 and 4.5 generations and different concentrations. Increasing generation number provides greater loaded naproxen amounts and larger particle size. Moreover, formulations provide controlled release at simulated terminal ileum conditions. Consequently, Jeffamine-cored carboxylic acid-terminated PAMAMs can be a promising option for oral drug delivery of poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]