Low Molecular Weight Products Research Articles

Коррозионная стойкость газопламенных полимерных покрытий, модифицированных неорганическими добавками

Исследовано влияние концентрации и дисперсности микроразмерного неорганического модификатора (ситалл, алюминиевая пудра) на коррозионную стойкость полимерного композиционного материала (ПКМ) газопламенных покрытий на основе полиэтилентерефталата (ПЭТФ), полиэтилена высокого давления (ПЭВД) и полиамида (ПА-6). Получена зависимость уровня коррозионной стойкости от дисперсности и концентрации наполнителя.

Study of The Reaction Mechanism to Produce Nanocellulose-Graft-Chitosan Polymer.

Cellulose and chitin are the most abundant polymeric materials in nature, capable of replacing conventional synthetic polymers. From them, cellulose nano/microfibers (CNFs/CMFs) and chitosan are obtained. Both polymers have been used separately in graft copolymerization but there are not many studies on the use of cellulose and chitosan together as copolymers and the reaction mechanism is unknown. In this work, the reaction mechanism to produce nano/microcellulose-graft-chitosan polymer has been studied. Recycled cellulose pulp was used, with and without a 2,2,6,6-tetramethylpiperidin-1-oxyl-radical (TEMPO)-mediated oxidation pretreatment, to produce CNFs and CMFs, respectively. For chitosan, a low-molecular weight product dissolved in an acetic acid solution was prepared. Grafted polymers were synthesized using a microwave digester. Results showed that TEMPO-mediated oxidation as the cellulose pretreatment is a key factor to obtain the grafted polymer CNF-g-CH. A reaction mechanism has been proposed where the amino group of chitosan attacks the carboxylic group of oxidized cellulose, since non-oxidized CMFs do not achieve the desired grafting. 13C NMR spectra, elemental analysis and SEM images validated the proposed mechanism. Finally, CNF-g-CH was used as a promising material to remove water-based inks and dyes from wastewater.

Comparative study on ferrate oxidation of BPS and BPAF: Kinetics, reaction mechanism, and the improvement on their biodegradability

Bisphenol S (BPS) and bisphenol AF (BPAF) were increasingly consumed and these compounds are resistant to environmental degradation. Herein, ferrate oxidation of BPS and BPAF was investigated, and biodegradability of the oxidation products was examined. The second-order reaction rate constants of ferrate with BPS and BPAF were 1.3 × 103 M−1s−1 and 3 × 102 M−1s−1, respectively, at pH 7.0, 25 °C. In the oxidation process, some BPS molecules dimerized, while other BPS molecules were oxidized through oxygen-transfer process, leading to the formation of hydroxylation products and benzene-ring cleavage products. The dominant reaction of BPAF with ferrate was oxygen-transfer process, and BPAF was degraded into lower molecular weight products. The variation of assimilable organic carbon (AOC) suggested that the biodegradability of BPAF and BPS was largely improved after ferrate oxidation. Compared with the BPS oxidation products, the BPAF oxidation products were easier to be bio-consumed. Pure culture test showed that BPAF inhibited the growth of Escherichia coli, while ferrate oxidation completely eliminated this toxic effect. Co-existing humic acid (HA, 1 mg C/L to 5 mg C/L) decreased the removal of BPS and BPAF with ferrate. Compared with BPAF, more oxidation intermediates formed in the ferrate oxidation of BPS may be reduced by HA to the parent molecular. Thus, the inhibition effect of HA on the ferrate oxidation of BPS was more obvious than that on BPAF.

Recent Efforts to Prevent Undesirable Reactions From Fractionation to Depolymerization of Lignin: Toward Maximizing the Value From Lignin

Lignin is a major component of lignocellulosic biomass along with cellulose and hemicellulose, currently underutilized with the bulk of technical lignin being combusted for heat generation in plant. From the technoeconomic perspective, the success of a future biorefinery is highly dependent on lignin valorization. However, structural complexity, heterogeneity of lignin, and several undesirable reactions associated with the nature of lignin and process conditions obstruct the effective utilization of lignin. Lignin condensation has been a long-lasting problem from conventional to recent biorefineries, which makes the recovered lignin more difficult to decompose. Also, the undesirable condensation and repolymerization during the depolymerization of lignin is more problematic as this significantly limits its ability to be depolymerized to low molecular weight products at high yields. To solve this problem, which ultimately enables maximizing lignin utilization, there have been many efforts in various aspects. In this review, we focus on the undesirable reactions occurring during the fractionation and depolymerization process of lignin and introduce recent efforts to suppress or minimize those unwanted reactions. The aim of all these efforts is to maximize lignin conversion to low molecular weight products.

Oxidative conversion of lignin over cobalt-iron mixed oxides prepared via the alginate gelation

The depolymerization of polymer lignin model to low molecular weight products was studied in water, at 200 °C under 100 MPa of 10% O2 using cobalt-iron mixed oxides as catalysts. These nanostructured oxides with different Co/Fe ratios were prepared via alginate gelation. X-ray diffraction, scanning electron microscope, and size exclusion chromatography were used to study the influence of the Fe/Co ratios on the structure and the proprieties of the oxides as well as the morphology, the structure, and the composition of the obtained degraded products. The results showed that the oxides used in this study were versatile catalysts with a high catalytic activity for lignin depolymerization. Furthermore, these oxides demonstrated high yield and high selectivity towards aromatic compounds.

RSM-CCD optimized In-air synthesis of photocatalytic nanocomposite: Application in removal-degradation of toxic brilliant blue

The present research work describes the synthesis of a nanocomposite hydrogel [BFO/Mr-cl-poly(AAm)-IPN-poly(AA)] from nano bismuth iron oxide (BFO) synergistically coupled with interpenetrating network (IPN: Mr-cl-poly(AAm)-IPN-poly(AA)) of acrylic acid (AA) created within crosslinked network of a semi-IPN (Mr-cl-poly(AAm)). Semi-IPN was previously synthesized from N, N′-methylene bisacrylamide (MBA) crosslinked (cl) network of polyacrylamide (poly(AAm)) grafted onto aqueous extract of Commiphora mukul (Mr). The synthesized sample was efficient in removal-degradation of Coomassie brilliant blue G-250 (CBB) dye. Nanocomposite (NC) was magnetic as well as photocatalytic. Initially, optimization of the reaction parameters was carried out using Response Surface Methodology (RSM) design. Significant variables were accessed using Minimum Resolution V design and further optimized conditions were evaluated with central composite design (CCD). Semi-IPN showed maximum % swelling of 833.8% showing interdependence of time-temperature and solvent-crosslinker concentration. IPN synthesized gave maximum swelling of 285.8%. On insertion of BFO nanoparticles, the NC synthesized could remove-degrade a maximum of 90.4% dye in sunlight and 88.6% in UV–visible light under optimized parameters: 600 mg NC dose, 10 ppm initial dye concentration, pH 7.0, removal and degradation time 25 h and 4 h, respectively. The whole process showed second order kinetics with Elovich model criteria and followed Langmuir adsorption isotherm. GC-MS analysis gave low molecular weight products as an evidence of degradation process. Also, the NC synthesized can be recycled for industrial use.

Wplyw budowy ukladu katalitycznego i warunkow polimeryzacji utleniajacej 2,6-dimetylofenolu na wydajnosc i mase molowa poli(tlenku fenylenu)

The activities of catalytic systems CuX2/L [where: X = Brˉ, Clˉ, L = dibutylamine, N,N-dimethylbutylamine (DBA), N-methylaminopropyltrimetoxysilane, morpholine] in the oxidative polymerization of 2,6-dimethylphenol (2,6-DMP) to poly(phenylene oxide) (PPO) were compared. The effects of 2,6-DMP/Cu molar ratio (500—750) in the most active CuBr2/dibutylamine system and the composition of toluene/hexane mixture as reaction medium on the PPO yield and molar mass were investigated. The CuBr2/DBA system (molar ratio 2,6-DMP/Cu = 250) allowed to obtain the highest yield (90.4 %) of PPO with the highest molar mass (67 900 g/mol). It has been found that in the presence of CuBr2/DBA during a dozen or so minutes after completing monomer dosing, low molecular weight product (5000 g/mol) was produced, after one hour polymer with molar mass typical for commercial species (56 800 g/mol) was produced, and further extending of the time did not significantly affect the molar mass of the product. The introduction of additional amine (N,N-dimethylbutylamine or N,N’-di-t-butylethylenediamine) enabled PPO synthesis with high yield and molar mass typical for that of commercial polymer at lower dibutylamine to Cu molar excess. The use of solvent/non-solvent mixture turned out to be ineffective in the synthesis of PPO.

A modified kinetic analysis method of cellulose pyrolysis based on TG–FTIR technique

The pyrolysis characteristics of cellulose was investigated using TGA and TG–FTIR. An modified reaction model was proposed to study cellulose pyrolysis. In this model, the active cellulose (E=137 kJ/mol) and dehydrocellulose (E=91.3 kJ/mol) were formed by parallel mechanism. The degradation of the active cellulose was followed by two competitive pathways, this is, one that formed levoglucosan (E=159.2 kJ/mol) and another that formed furan and some low molecular weight products (E=203.5 kJ/mol). The random scission model was used to describe the kinetics of cellulose pyrolysis. The same kinetic parameters were used for different linear heating rates (10–100 °C/min) and isothermal segment conditions. By successfully modeling non-isothermal and isothermal segment data, the model was proved to be credible in describing cellulose pyrolysis.

Nano-peroxidase fabrication on cation exchanger nanocomposite: Augmenting catalytic efficiency and stability for the decolorization and detoxification of Methyl Violet 6B dye

Abstract In present study polypyrrole-zirconium(IV)selenoiodate cation exchanger nanocomposite (PZrSeI-CENC) was employed to immobilize ginger peroxidase (GP) via strong electrostatic interactions. Fourier transform infrared spectroscopy, transmission electron microscopy and scanning electron microscopy was done to characterize the PZrSeI-CENC before and after immobilization of GP. PZrSeI-CENC bound GP exhibited very high activity yield of around 96%. Immobilized GP was less sensitive to the changes in pH and temperature compared to free GP. In stirred batch processes immobilized GP was able to decolorize around 96% of the Methyl Violet 6B (MV 6B) dye after 3 h of incubation whereas only 81% of the dye was decolorized by free GP under identical experimental conditions. Immobilized GP exhibited excellent reusability in the stirred batch process and decolorized around 60% of the dye even after its 10th repeated use. Furthermore, Vmax of PZrSeI-CENC bound GP was amplified 10 times which is mainly attributed to polypyrrole aided enhanced electron shuttle system of the enzyme. A degradation pathway was proposed in compliance with gas chromatography-mass spectroscopy analysis that confirms the degradation of MV 6B into low molecular weight products. The genotoxic assessment revealed a significant reduction in toxicity of dye after treatment with nanocomposite bound peroxidase.

Modification of native fucoidan from Fucus evanescens by recombinant fucoidanase from marine bacteria Formosa algae

Enzymatic depolymerization of fucoidans attracts many researchers due to the opportunity of obtaining standardized fucoidan fragments. Fucoidanase catalyzes the cleavage of fucoidan from Fucus evanescens (FeF) to form low molecular weight products (LMP) and a polymeric fraction (HMP) with 50.8 kDa molecular weight and more than 50% yield. NMR spectroscopy shows that the HMP fraction has regular structure and consists of a repeating fragment [→3)-α-l-Fucp2,4OSO3−-(1 → 4)-α-l-Fucp2,4OSO3−-(1 → 4)-α-l-Fucp2OSO3−-(1→]n. The anticancer effects of FeF fucoidan and its derivative (HMP) were studied in vitro on colon cancer cells HCT-116, HT-29, and DLD-1. The anticancer activity of the HMP fraction was found to be slightly lower than that of the FeF fucoidan. Research and practical applications of the enzyme include modification of native fucoidans for purposes of regular and easier characterized derivatives acquisition.

Microbial Degradation of Coal into a Value Added Product

ABSTRACTMicrobial treatment has been considered as an economic, effective and environment safe way of processing coal via degradation of the macromolecular network into simpler, low molecular weight products. The present work is intended to observe the feasibility of microbial attack on reject coal, having high ash content (65% ash). The results indicated that microorganisms were able to change and modify the macro molecular structure of reject coal. This paper summarizes the potential ability of the microorganisms to beneficiate reject coal and to make a value-added product, humic acid from reject coal. This work describes the status of current and the probable directions of the future research.

Products of Metabolism and Processing of Lactic Acid Bacteria as Functional Ingredients

Lactic acid bacteria (LAB) and bifidobacteria (BB) are unique substances that have a lot of biological and physiological effects. Structural components of LAB and BB – peptidoglycans, compounds of the muramylpeptide series, teichoic acids – have powerful immunological properties. Metabolites of LAB and BB – organic acids, hydrogen peroxide, bacteriocins, etc. – provide antagonistic activity, have an indirect impact on the immune system, reducing the antigenic load caused by pathogenic microorganisms. The expediency of peptidoglycans degradation of LAB and BB cell walls is substantiated. Low molecular weight products of the degradation can easily be absorbed and enter into biochemical processes, accelerating the expected functional-physiological effect. To obtain low-molecular products of peptidoglycans degradation, a combination of LAB and BB was used. The combination of LAB and BB is the sum of the test cultures of Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. Bulgaricus, Bifidobacterium bifidum, Lactococcus cremoris, Streptococcus termophilus. Destruction of peptidoglycans of bacterial cell walls was carried out using a combination of disintegrating factors. The efficiency of destruction was determined by the accumulation of low molecular weight peptides (with molecular weight up to 1500 Da), amino acids and soluble protein in the disintegrate. It has been established that the highest accumulation of low molecular weight degradation products occurs when using autolysis followed by enzymatic hydrolysis during 180 min with the ratio of the enzyme : substrate 1 : 100. At the same time ≈ 53% of protein substances pass from insoluble to soluble state. The molecular weight of the obtained products is determined by the gel chromatography method. The qualitative and quantitative content of organic acids, amino acids and vitamins of group В in the hydrolysis products composition was investigated. It was shown that the obtained product possesses high biological effect in the experiment on animals.

Quantum chemical study of the impact of protective association on the chemoselective synthesis of carboxybetaine from 2-(dimethylamino)ethanol and acrylic acid

Abstract Targeted carboxybetaine synthesis is an important process that one can apply to prepare polymeric materials with various unique properties or low molecular weight products, such as deep eutectic solvents based on acrylic acid formulated for the specific tasks. Analyzing the mechanism of carboxybetaine formation, it was found that with an excess of amine, the H-bond formed between amine nitrogen and the acidic proton of the acrylic acid was strong enough to protect the intermediate obtained after carbanion protonation from the interaction with acrylate anion, thus facilitating the formation of quaternary ammonium salts as the final product at the beginning of the reaction instead of the desired carboxybetaine. Similarly, a threefold excess of acrylic acid should also lead to the preferential formation of the quaternary salt due to the protection of the half-product from the interaction with acrylate anion via cyclic dimer formation with two strong H-bonds. From the other side, calculations revealed that a twofold excess of acrylic acid should provide formation of carboxybetaine as the dominant product. The discussed energy profiles were supplemented with extensive natural bond order analysis in the course of which delocalization energies were calculated and used to discuss the strength of intermolecular donor–acceptor interactions within the considered molecular systems.

The Effect of Transfer Factor as Immunoprotective in Mice Challenged with <i>Mycobacteriu</i>m <i>tuberculosis</i>

Background: Transfer Factor (TF) is an immune modulator which stimulates the cellular arm of the immune system (killer lymphocytes), activates immune cytokine synthesis and regulates immune function [1]. TF is very effective in those diseases in which CMI plays a relevant role in protection and control of the disease, such as intracellular bacterial diseases (tuberculosis) [2]. TF are low molecular weight products from immune cells that are able to transmit the ability to express delayed-type hypersensitivity (DTH) and cell mediated immunity (CMI) from sensitized donors to non immune recipients [3]. Objectives: The aim of this experimental study is to determine the protective efficacy of transfer factor (TF) as immunotprotective for mice. Materials and methods: A total number of 82 mice were examined for their immunopotency and protective efficacy of Transfer factor (TF) against challenge dose of M. tuberculosis (107 CFU). A number of 20 mice were immunized with the attenuated strain of M. bovis, Bacillus Calmette-Guerin (BCG). After 21 days of BCG spleens of 10 tuberculous mice were removed aseptically for the preparation of TF. To evaluate the effect of TF 3 groups of inbred BALB/c male mice were injected with TF and challenged with virulent M. tuberculosis, All mice with TF were tested for tuberculin skin test (TST) so as to determine susceptibility and resistance against tuberculosis, susceptible groups of mice were challenged with virulent M. tuberculosis.Followed by study of humoral response by immunization of a group of mice with immune sera and challenged with M. tuberculosis H37Rv strain. Followed by an experiment of group A and B for the susceptibility and resistance of the strains of mice. Results: After three weeks of observations the mice of experiment were tested for tuberculin skin test and the results were positive. Effectiveness determination of TF as protective efficacy was (83.3%). Humoral immunity response against M. tuberculosis showed negative reaction hence mortality rate was 100%, group B mice were resistant for BCG (Swiss white strain). Conclusions: The results indicated that administration of murine transfer factor (mTF) extracted and prepared from spleen of animal model (mice) as immunoprotective for challenged mice of M. tuberculosis (H37Rv) showed a better results enhanced immune response in respect to delayed type hypersensitivity, survival rate and mortality rate suggesting that efficacy of mTF as immunotherapy for tuberculosis.

A method of GC-MS analysis of serum metabolites

Metabolites are the intermediate and natural low molecular weight products of metabolic reactions that naturally occur within cells. Metabolomics is a post-genomics study that analyzes metabolic profile in all biological samples. Gas chromatography-mass spectrometry (GC-MS) is a powerful technique that detects volatile components. In this study we evaluate the metabolite profile of serum with a simple method for derivatization. The metabolic profile of serum taken from 16 rats was analyzed using GC-MS after protein precipitation with acetonitrile. Then, it was derivatized with a method requiring the less number and volume of materials. Acquisition chromatograms were pre-processed and analyzed using National Institute of Standards and Technology (NIST) library. We detected 35 metabolites with probability of >60% perfect match according to spectrum fragments analysis by NIST library.This study represents the metabolome profile of serum instead the change of metabolites that can be evaluated by a simple derivatization method.

Structural Properties of the RNA Synthesized by Glutamate Dehydrogenase for the Degradation of Total RNA

Glutamate dehydrogenase (GDH)-synthesized RNA, a nongenetic code-based RNA is suitable for unraveling the structural constraints imposed on the regulation (transcription, translation, siRNA etc.) of metabolism by genetic code. GDH-synthesized RNAs have been induced in whole plants to knock out target mRNA populations thereby producing plant phenotypes that are allergen-free; enriched in fatty acids, essential amino acids, shikimic acid, resveratrol etc. Methods applied hereunder for investigating the structural properties of GDH-synthesized RNA included purification of GDH isoenzymes, synthesis of RNA by the isoenzymes, reverse transcription of the RNA to cDNA, sequencing of the cDNA, computation of the G+C-contents, profiling the stability through PCR amplification compared with genetic code-based DNA; and biochemical characterization of the RNAs synthesized by individual hexameric isoenzymes of GDH. Single product bands resulted from the PCR amplification of the cDNAs of GDH-synthesized RNA, whereas several bands resulted from the amplification of genetic code-based DNA. The cDNAs have wide G+C-contents (35% to 59%), whereas genetic code-based DNA has narrower G+C-contents (50% to 60%). The GDH β6 homo-hexameric isoenzyme synthesized the A+U-rich RNAs, whereas the a6, and α6 homo-hexameric isoenzymes synthesized the G+C-rich RNAs. Therefore, the RNA synthesized by GDH is different from genetic code-based RNAs. In vitro chemical reactions revealed that GDH-synthesized RNA degraded total RNA to lower molecular weight products. Therefore, GDH-synthesized RNA is RNA enzyme. Dismantling of the structural constraints imposed on RNA by genetic code liberated RNA to become an enzyme with specificity to degrade unwanted transcripts. The RNA enzyme activity of GDH-synthesized RNA is ubiquitous in cells; it is readily induced by treatment of plants with mineral nutrients etc. and may simplify experimental approaches in plant enzymology and molecular biology research projects.

Involvement of the Transcriptional Coactivator ThMBF1 in the Biocontrol Activity of Trichoderma harzianum.

Trichoderma harzianum is a filamentous fungus well adapted to different ecological niches. Owing to its ability to antagonize a wide range of plant pathogens, it is used as a biological control agent in agriculture. Selected strains of T. harzianum are also able to increase the tolerance of plants to biotic and abiotic stresses. However, little is known about the regulatory elements of the T. harzianum transcriptional machinery and their role in the biocontrol by this species. We had previously reported the involvement of the transcription factor THCTF1 in the T. harzianum production of the secondary metabolite 6-pentyl-pyrone, an important volatile compound related to interspecies cross-talk. Here, we performed a subtractive hybridization to explore the genes regulated by THCTF1, allowing us to identify a multiprotein bridging factor 1 (mbf1) homolog. The gene from T. harzianum T34 was isolated and characterized, and the generated Thmbf1 overexpressing transformants were used to investigate the role of this gene in the biocontrol abilities of the fungus against two plant pathogens. The transformants showed a reduced antifungal activity against Fusarium oxysporum f. sp. lycopersici race 2 (FO) and Botrytis cinerea (BC) in confrontation assays on discontinuous medium, indicating that the Thmbf1 gene could affect T. harzianum production of volatile organic compounds (VOC) with antifungal activity. Moreover, cellophane and dialysis membrane assays indicated that Thmbf1 overexpression affected the production of low molecular weight secreted compounds with antifungal activity against FO. Intriguingly, no correlation in the expression profiles, either in rich or minimal medium, was observed between Thmbf1 and the master regulator gene cross-pathway control (cpc1). Greenhouse assays allowed us to evaluate the biocontrol potential of T. harzianum strains against BC and FO on susceptible tomato plants. The wild type strain T34 significantly reduced the necrotic leaf lesions caused by BC while plants treated with the Thmbf1-overexpressing transformants exhibited an increased susceptibility to this pathogen. The percentages of Fusarium wilt disease incidence and values of aboveground dry weight showed that T34 did not have biocontrol activity against FO, at least in the ‘Moneymaker’ tomato variety, and that Thmbf1 overexpression increased the incidence of this disease. Our results show that the Thmbf1 overexpression in T34 negatively affects its biocontrol mechanisms.

Understanding interactions between lignin and ionic liquids with experimental and theoretical studies during catalytic depolymerisation

Compared to H2SO4, Brønsted acidic ionic liquid (BAIL, [C3SO3HMIM][HSO4]) catalyzed depolymerization of lignin yielded higher concentration of low molecular weight products under mild conditions (120°C) as proven by GC and GC–MS. To comprehend this disparity in catalytic activity among H2SO4 and BAIL (at similar H+ concentration), experimental techniques [1D(1H) NMR, 2D(15N/1H HMBC) NMR and RAMAN] have been employed. Based on these studies, it has been proven that the transfer of electron density from substrate to the electron deficient imidazolium ring via formation of hydrogen bond between OH/OCH3 (substrate) and N1C2H2N3− (cation) is possible, while the anion plays an important role. Further, density functional theory (DFT) calculations also corroborated this fact by showing a change in the bond angle and decrease in bond length (C2H2 in imidazole), due to the presence of weak and strong hydrogen bonding between the substrate and IL.

PAMAM Dendrimers Attached to Collagen via a Malondialdehyde Linker

AbstractFunctionalization of polyamidoamine dendrimers (PAMAM) for use as macromolecular drug carriers with aldehydes was performed using aminoacetaldehyde dimethylacetal (AADA) and malondialdehyde (MDA). AADA was used to obtain low molecular weight product upon reaction with dimethyl succinate and PAMAM G‐0.5. The structure of succinate bis‐(dimethylacetal)acetamide was elucidated by X‐ray crystallography. This product, as well as the product of condensation of PAMAM G‐0.5 with AADA, were resistant to hydrolysis. MDA reacted with iso‐butylamine and polyamidoamine PAMAM G0 dendrimers to give 3‐[N‐(2‐methylpropyl)amino]prop‐2‐enal and PAMAM G0 with four arms ending with prop‐2‐enal groups. The compounds were characterized by NMR, MS and/or elemental analysis. PAMAM G3 was also converted to aldehyde‐terminated dendrimer with excess MDA, however, the product was water insoluble. The low molecular weight water soluble analogue prop‐2‐enal terminated PAMAM G0 dendrimer was tested for toxicity on normal human fibroblasts and glioblastoma cell cultures. The toxicity of prop‐2‐enal terminated PAMAM G0 was comparable with that of amine ending PAMAM G0. Finally, fluorescein‐labeled PAMAM G3 was covalently attached to a collagen scaffold via a MDA linker as demonstrated by confocal microcopy. This rapid method of covalent attachment of PAMAM‐drug conjugates to MDA‐activated collagen opens new pathways for delivery of drugs into tissue.

Effect of increased surface hydrophobicity via drug conjugation on the clearance of inhaled PEGylated polylysine dendrimers.

PEGylated polylysine dendrimers are attractive and well tolerated inhalable drug delivery platforms that have the potential to control the release, absorption kinetics and lung retention time of conjugated drugs. The clinical application of these systems though, would likely require partial substitution of surface PEG groups with drug molecules that are anticipated to alter their lung clearance kinetics and clearance pathways. In the current study, we therefore evaluated the impact of increased surface hydrophobicity via substitution of 50% surface PEG groups with a model hydrophobic drug (α-carboxyl OtButylated methotrexate) on the lung clearance of a Generation 5 PEGylated polylysine dendrimer in rats. PEG substitution with OtBu-methotrexate accelerated lung clearance of the dendrimer by increasing polylysine scaffold catabolism, improving systemic absorption of the intact dendrimer and low molecular weight products of scaffold catabolism, and enhancing mucociliary clearance. These results suggest that the conjugation of hydrophobic drug on the surface of a PEGylated dendrimer is likely to accelerate lung clearance when compared to a fully PEGylated dendrimer.