Density Functional Theory Study of the Reaction Behavior Histidine Modified Polyamidoamine Dendrimer as Nanocarrier for Delivery of Ectoine Drug

Fundamentals of Nanotechnology in Drug Delivery.- Physicochemical Principles of Nanosized Drug Delivery Systems.- Block Copolymer Synthesis for Nanoscale Drug and Gene Delivery.- Supercritical Fluid Technology for Nanotechnology in Drug Delivery.- Nanotubes, Nanorods, Nanofibers, and Fullerenes for Nanoscale Drug Delivery.- Drug Loading into and In Vitro Release from Nanosized Drug Delivery Systems.- Nanotechnology-Based Biosensors in Drug Delivery.- Biopharmaceutical, Physiological, and Clinical Considerations for Nanotechnology in Drug Delivery.- Nanomaterials and Biocompatibility: BioMEMS and Dendrimers.- Nanomaterials and Biocompatibility: Carbon Nanotubes and Fullerenes.- Factors Controlling Pharmacokinetics of Intravenously Injected Nanoparticulate Systems.- Controlled Release and Nanotechnology.- Nanotechnology for Intracellular Delivery and Targeting.- Nanotechnology for the Delivery of Small Molecules, Proteins and Nucleic Acids.- Nano-sized Advanced Delivery Systems as Parenteral Formulation Strategies for Hydrophobic Anti-cancer Drugs.- Engineering of Amphiphilic Block Copolymers for Drug and Gene Delivery.- PAMAM Dendrimers as Nanoscale Oral Drug Delivery Systems.- Nanoemulsions for Intravenous Drug Delivery.- Nanotechnology for Cancer Chemotherapy.- Nanotechnology for Cancer Vaccine Delivery.- Stimuli-Sensitive Nanotechnology for Drug Delivery.- A Look to the Future of Nanotechnology in Drug Delivery.- Nanotechnology in Drug Delivery: Past, Present, and Future.- Nanotechnology in Drug Development and Life Cycle Management.- Nanopharmaceuticals: Challenges and Regulatory Perspective.

Poly(amidoamine) dendrimers are very interesting macromolecules with highly branched structures and globular-shaped branched polymeric architectures. They are widely used for drug and gene delivery applications. In order to provide important insight into the interactions of poly(amidoamine) dendrimers with some organic acceptors, the binding of small molecules to 4-hexylamino-1,8-naphthalimide-labelled PAMAM dendrimer (PD) have been studied by spectrophotomeric method. The acceptors used in this research include chloranilic acid (CLA), p-chloranil (CHL), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), 7,7ʹ,8,8ʹ-tetracyanoquinodimethane (TCNQ), picric acid (PA), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and iodine monobromide (IBr). The spectrophotometric measurements proved that all the charge-transfer (CT) complexes are formed via a stoichiometry (PD: acceptor) of 1:2 (except for IBr acceptor). Accordingly the obtained complexes could be formulated as [(PD)(CLA)2], [(PD)(DCQ)2], [(PD)(DBQ)2], [(PD)(TCNQ)2], [(PD)(PA)2], [(PD)(CHL)2], [(PD)(DDQ)2] and [(PD)(IBr)4]. Benesi–Hildebrand and its modification methods were applied to estimate the spectroscopic and physical data.

Poly(amidoamine) (PAMAM) dendrimers are proposed as one of the most promising nanomaterials for biomedical applications because of their unique tree-like structure, monodispersity and tunable properties. In this study, we found that PAMAM dendrimers could induce the formation of autophagosomes and the conversion of microtubule-associated protein 1 light chain 3 (LC3) in hepatocellular carcinoma HepG2 cells, while the inhibition of the Akt/mTOR and activation of the Erk 1/2 signaling pathways were involved in autophagy-induced by PAMAM dendrimers. We also investigated the suppression of autophagy with the obviously enhanced cytotoxicity of PAMAM dendrimers. Moreover, the blockage of a reactive oxygen species (ROS) could enhance the growth inhibition and apoptosis of hepatocellular carcinoma cells, induced by PAMAM dendrimers through reducing autophagic effects. Taken together, these findings explored the role and mechanism of autophagy induced by PAMAM dendrimers in HepG2 cells, provided new insight into the effect of autophagy on drug delivery nanomaterials and tumor cells and contributed to the use of a drug delivery vehicle for hepatocellular carcinoma treatment.

Starburst® PAMAM dendrimers are potential carriers for drug delivery due to their unique structure. Drug-delivery scaffolds were designed and built up based on the polyethylene glycolpolyamidoamine (PEG-PAMAM) star polymer. Penicillin V was used as a model carboxylic group containing drug to conjugate with full- and half-generation PAMAM dendrimers. G2.5 PAMAM (with 32 carboxylic groups on the surface) dendrimers and G3.0 (with 32 primary amine groups on the surface) were typically chosen. There are two strategies given in the paper where a drug carrying a carboxylic group (e.g. penicillin V) was coupled to star polymer via amide and ester bonds, respectively. FT-IR, UV-Vis and 1H-NMR were used to characterize the intermediates and drug-star polymer conjugates. A single-strain bacterium, Staphylococcus aureus, was grown up for penicillin-conjugated PEG-PAMAM (G3.0) star polymer activity test. The result verified the bioavailability of modified penicillin after the ester bond was cleaved.

SYNTHESIS AND CHARACTERIZATION OF POLYIONIC HYDROGELS By Pooja N Desai M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Biomedical Engineering at Virginia Commonwealth University. Virginia Commonwealth University, 2008 Major Director: Dr. Hu Yang Assistant Professor Biomedical Engineering In this study we describe novel polyionic dendrimer – PEG hydrogels for drug delivery. Hydrogels have a crosslinked insoluble network of polymer chains, which have found many applications including drug delivery and tissue regeneration. Dendrimers provide an ideal platform for drug delivery as they possess a well-defined highly branched nanoscale architecture with many reactive surface groups. Their highly clustered surface groups allow for targeted drug delivery and high drug payload to enhance therapeutic effectiveness. This study presented a new type of polyionic hydrogels based on dendrimers with potential applications in drug delivery and tissue engineering. Polyethylene glycol (PEG) with various chain lengths [1500, 6000 , 12000 Da] was first conjugated to the StarburstTM G3.0 PAMAM dendrimer to form stealth dendrimers through one ending site of PEG using p-nitro phenyl chloroformate and Triethylamine. The free hydroxyl group of PEG was further converted to an acrylate group using acrolyl chloride and Triethylamine. The conjugation was characterized with H-NMR. The Ninhydrin assay was used to estimate the loading degree of PEG on the dendrimer surface. The molecular weight and loading degree of PEG was varied. Hydrogel formation was realized by subjecting dendrimer-PEG acrylate to UV exposure for a brief period of time at the presence of Eosin Y, Triethanolamine [TEOA] and 1 vinyl 2 Pyrrolidinone [NVP] photo initiator system. Viscosity increase was observed after hydrogel formation. PEGylated G3.0 PAMAM dendrimer served as cross-linking agent to form hydrogels because of its multiple functionalities. PEGylated half generation dendrimer G3.5 was subjected to hydrogel formation and its swelling behavior was studied. Better hydrogel formation was observed with increased PEG arm length. The surface charges conferred by terminal groups on the dendrimer surface made the hydrogel polyionic with controllable charge density. This new type of hydrogel has many favorable biological properties such as non toxicity and non immunogenecity and multifunctional ties for a variety of in vivo applications. Current studies have demonstrated feasibility of chemistry and hydrogel formation. The swelling studies demonstrated pH sensitive behavior. Degradation of hydrogel was observed, for low PEGylated dendrimer degradation also demonstrated pH sensitivity. Controlled drug delivery and release were also investigated. Hydrophobic drug Cyclosprine A was used, we envision that hydrophobic dendrimer core will used for drug encapsulation and delivery, and later release in controlled fashion. The polymer and hydrogels were evaluated for in vitro cytotoxicity and cell internalization.

Recently, graphene and modified graphene as one of the most suitable and the most important carbon nanomaterials have been introduced for drug delivery. In this paper, we have studied the binding characteristics of the EDC-NHS cross-linking process of graphene-phenyl-NH2 and 5-aminolevulinic acid (ALA) drug in both gas and solvent phases by density functional theory calculations. For describing binding properties and reaction nature between graphene-ghenyl-NH2 and ALA drug, quantum molecular descriptors, topological analysis, natural bond orbital analysis, analysis of the bond order, the density of states, and analysis bond length was investigated in solvent and gas phases. Due to the results, the complex of the graphene-phenyl-NH2 @ALA turns to absorb more electrons in water solvent than gas phase. Furthermore, the binding of graphene-phenyl-NH2 and ALA is mainly based on covalent interactions, and bond order of graphene-phenyl-NH2 @ALA complex is one in solvent and gas phases. The praphene-phenylNH2 @ALA complex has displayed a meaningful improvement of electronic and structural properties. Therefore, it represented that praphene-phenyl-NH2 being combined with the ALA drug is appropriate for use in drug delivery.

Developmental toxicity of low generation PAMAM dendrimers in zebrafish

This study focuses on ambient-temperature self-crosslinking acrylic latex coating compositions containing poly(amidoamine) (PAMAM) dendrimers and ZnO nanoparticles in the role of inter-particle cross-linking agents and flash rust inhibitors. Low-generation amine-terminated PAMAM dendrimers as aqueous solutions were added into latices containing diacetone acrylamide repeat units in their polymer structure. The incorporation of ZnO nanoparticles (without any surface treatment) was performed during the synthesis of a polymer dispersion carried out by the semi-continuous emulsion polymerization technique. The latex storage stability and coating performance with respect to zinc oxide and PAMAM presence were evaluated and compared with a conventional zinc oxide-free coating composition containing adipic acid dihydrazide as the cross-linking agent. It was found that the novel latices containing both PAMAM dendrimers and ZnO nanoparticles exhibited a long-term storage stability and provided crosslinked transparent coating films of high gloss, enhanced mechanical properties, solvent resistance and excellent water whitening resistance. Moreover, the latex compositions containing PAMAM dendrimers as the inter-particle cross-linkers were shown to provide flash rust resistance.

A new class of dendrimers, the poly(propyl ether imine) (PETIM) dendrimer, has been shown to be a novel hyperbranched polymer having potential applications as a drug delivery vehicle. Structure and dynamics of the amine terminated PETIM dendrimer and their changes with respect to the dendrimer generation are poorly understood. Since most drugs are hydrophobic in nature, the extent of hydrophobicity of the dendrimer core is related to its drug encapsulation and retention efficacy. In this study, we carry out fully atomistic molecular dynamics (MD) simulations to characterize the structure of PETIM (G2-G6) dendrimers in salt solution as a function of dendrimer generation at different protonation levels. Structural properties such as radius of gyration (Rg), radial density distribution, aspect ratio, and asphericity are calculated. In order to assess the hydrophilicity of the dendrimer, we compute the number of bound water molecules in the interior of dendrimer as well as the number of dendrimer-water hydrogen bonds. We conclude that PETIM dendrimers have relatively greater hydrophobicity and flexibility when compared with their extensively investigated PAMAM counterparts. Hence PETIM dendrimers are expected to have stronger interactions with lipid membranes as well as improved drug encapsulation and retention properties when compared with PAMAM dendrimers. We compute the root-mean-square fluctuation of dendrimers as well as their entropy to quantify the flexibility of the dendrimer. Finally we note that structural and solvation properties computed using force field parameters derived based on the CHARMM general purpose force field were in good quantitative agreement with those obtained using the generalized Amber force field (GAFF).

Removal of Co(II) from fuel ethanol by silica-gel supported PAMAM dendrimers: Combined experimental and theoretical study

Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy

The role of autophagy in the neurotoxicity of cationic PAMAM dendrimers

Ambient temperature self-crosslinking latices using low generation PAMAM dendrimers as inter-particle crosslinking agents

A series of actinide (An) species of L-An-N compounds [An = Pa-Pu, L = [N(CH2CH2NSiPr(i)3)3](3-), Pr(i) = CH(CH3)2] have been investigated using scalar relativistic density functional theory (DFT) without considering spin-orbit coupling effects. The ground state geometric and electronic structures and natural bond orbital (NBO) analysis of actinide compounds were studied systematically in neutral and anionic forms. It was found that with increasing actinide atomic number, the bond length of terminal multiple An-N1 bond decreases, in accordance with the actinide contraction. The Mayer bond order of An-N1 decreases gradually from An = Pa to Pu, which indicates a decrease in bond strength. The terminal multiple bond for L-An-N compounds contains one σ and two π molecular orbitals, and the contributions of the 6d orbital to covalency are larger in magnitude than the 5f orbital based on NBO analysis and topological analysis of electron density. This work may help in understanding of the bonding nature of An-N multiple bonds and elucidating the trends and electronic structure changes across the actinide series. It can also shed light on the construction of novel An-N multiple bonds.

The focus of this study is on compound clusters and, due to the existence of many phases with different structural properties, tin-based materials have been chosen as the reference case. The clusters considered below are of two types: in the first case the clusters have the skeleton of the pure tin clusters and are doped with oxygen and aluminum atoms with composition SnxYywith Y = Al, O, x = 1, 10 and y = 1, 2. In the second case the clusters have a rutile lattice with a columnar or a spherical shape and a size up to 80 atoms and are doped with a number of aluminum atoms up to 20. The calculations are based on the Density Functional Theory (DFT) and the results describe the cluster structure, its binding energy and the density of states (DOS). The general indication of the calculations is that the additive coordinates outside, rather than inside, the pristine skeleton with the formation of hybrid bonds with properties similar to the ones of the host atoms. Also conspicuous effects of hybridization are observed in the electronic structure and, due to these effects, the binding energy may decrease with respect to the one in the undoped clusters.