Construction of folate receptors and mitochondria targeting celastrol-loaded PAMAM nano-drug delivery system and its in vitro anti-inflammatory effect / 药学学报

Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.

Self-assembling dendrimers for biomedical applications / 中国药科大学学报

@#Dendrimers, a special class of synthetic polymers known for their well-defined ramified structures and unique multivalent cooperativity, hold great promise for various biomedical applications. However, preparation of defect-free dendrimers of high-generation on a large scale remains challenging because of the tedious and time-consuming synthesis as well as difficult purification. To overcome these limitations, an alternative strategy based on self-assembling approach has been developed to construct supramolecular dendrimers using small amphiphilic dendrimer-building units. By virtue of the amphiphilic nature, these small dendrimer-building units self-assemble and form large non-covalent supramolecular dendritic structures that mimic high-generation covalent dendrimers. Here, we present a brief overview of the supramolecular dendrimers developed in our group for the delivery of nucleic acid therapeutics, anticancer drug and imaging agents.

Research progress on the biomimetic remineralization of hard tooth tissues based on polyamide-amine dendrimer / 华西口腔医学杂志

Polyamide-amine (PAMAM) dendrimer, a new hyperbranched macromolecular polymer, is considered an "artificial protein" by many scholars on account of its excellent chemical and biological characteristics. PAMAM has internal cavities and a large number of reactive terminal groups. These structures allow the polymer to be used as a bionic macromoleculethat could simulate the biomimetic mineralization of the natural organic matrix on the surface of tooth tissue. Specifically, PAMAM can beused as an organic template to regulate mineral nucleation and crystal growth; thus, the polymerisa more ideal dental restoration material than traditional allogenic materials. This article reviews research progress on thePAMAM-induced biomimetic mineralization of hard tooth tissues.

TGA/Chemometrics addressing innovative preparation strategies for functionalized carbon nanotubes / 药物分析学报

In this work, functionalized carbon nanotubes (CNTs) using two polyamine polymers, polyethyleneimine (PEI) and polyamidoamine dendrimer (PAMAM), were investigated by thermal analysis in order to address preparation strategies to obtain low cytotoxic compounds with the ability to conjugate micro-RNAs and, at the same time, to transfect efficiently endothelial cells. Thermogravimetric analysis (TGA) was coupled to chemometrics as a novel analytical strategy to characterize functionalized CNTs from different preparation conditions. In particular, two starting materials were considered:very small CNTs and carboxylated CNTs (CNT-COOH) in order to examine the affinity with polymers. Chemometrics permitted to compare results from TGA and to investigate the effect of a number of factors affecting the synthesis of coated nanotubes including a different amount of involved polymer and the time required for the suspension for a satisfactory and reproducible preparation procedure. The results demonstrated the effectiveness of TGA as a tool able to address synthesis of coated CNTs to be employed as efficient drug delivery vectors in biomedical applications.

Modulation of Electroosmotic Flow through Skin: Effect of Poly(Amidoamine) Dendrimers

The objective of this work is to evaluate the effect of polyamidoamine (PAMAM) dendrimers on electroosmotic flow (EOF) through skin. The effect of size and concentration of dendrimer was studied, using generation 1, 4 and 7 dendrimer (G1, G4 and G7, respectively). As a marker molecule for the direction and magnitude of EOF, a neutral molecule, acetoaminophen (AAP) was used. The visualization of dendrimer permeation into the current conducting pore (CCP) of skin was made using G4–fluorescein isothiocyanate (FITC) conjugate and confocal microscopy. Without dendrimer, anodal flux of AAP was much higher than cathodal or passive flux. When G1 dendrimer was added, anodal flux decreased, presumably due to the decrease in EOF by the association of G1 dendrimer with net negative charge in CCP. As the generation increased, larger decrease in anodal flux was observed, and the direction of EOF was reversed. Small amount of methanol used for the preparation of dendrimer solution also contributed to the decrease in anodal flux of AAP. Cross-sectional view perpendicular to the skin surface by confocal laser scanning microscope (CLSM) study showed that G4 dendrimer-FITC conjugate (G4-FITC) can penetrate into the viable epidermis and dermis under anodal current. The permeation route seemed to be localized on hair follicle region. These results suggest that PAMAM dendrimers can permeate into CCP and change the magnitude and direction of EOF. Overall, we obtained a better understanding on the mechanistic insights into the electroosmosis phenomena and its role on flux during iontophoresis.

Estudo de síntese e estabilidades química e enzimática de fármaco dirigido dendrimérico potencialmente ativo em doença de Chagas / Synthesis, chemical and enzymatic stability studies of targeted dendrimer potentially active in Chagas disease

A doença de Chagas representa um problema de saúde pública em muitos países e regiões. O tratamento consiste em fármacos tóxicos, com eficácia discutível, principalmente, na fase crônica da doença. Assim, faz-se necessário o planejamento de novos quimioterápicos, mais seguros e eficazes. Os dendrímeros são novas arquiteturas moleculares formadas por um foco central e ramificações partindo desse foco. Apresentam diversas aplicações biológicas como, por exemplo, atuar como transportadores de fármacos. Face ao exposto, o objetivo deste trabalho foi o estudo de condições para ligar o ácido anacárdico (AA) em derivado dendrimérico com potencial ação na doença de Chagas, o qual tem como foco central o ácido succínico (AS) e ramificações compostas por arginina (Arg) e lisina (Lys). Sabe-se que a cruzaína, uma cisteíno-protease do T. cruzi, catalisa a hidrólise de ligação peptídica entre lisina e arginina. A síntese dos compostos em fase sólida forneceu os derivados brutos: (1) pró-fármaco AA-K-R-NH2 e (2) G.05 AA-K(AS)-R-NH2, que foram purificados e caracterizados por Cromatografia Líquida de Alta Eficiência e espectrometria de massas. Os compostos purificados AA-K-R-NH2 e AA-K(AS)-R-NH2 apresentaram rendimentos de 34% e 47%, com pureza de 88% e 98%, respectivamente. Os resultados dos experimentos enzimáticos utilizando o AA-K-R-NH2 não foram conclusivos. Acredita-se que a baixa solubilidade e/ou baixa concentração podem ter contribuído para tal. Já na estabilidade química em pH 7,4 (que simula pH sanguíneo), pH 1,2 (que simula pH estomacal) e pH 8,5 (que simula pH intestinal), observou-se que o AA-K(AS)-R-NH2 foi estável durante as 24 h de ensaio. Estes últimos resultados são interessantes, pois espera-se que o pró-fármaco dendrimérico alcance o T. cruzi estruturalmente integro, sofrendo hidrólise e liberação do composto ativo no interior do parasita

Chagas disease is a public health problem in many countries and regions. The treatment consists of toxic drugs, with debatable efficacy, mainly, in the chronic phase of the disease. Thus, it is necessary to plan new chemotherapeutics, safer and more effective than those drugs. Dendrimers are new molecular architectures composed by a central focus and branching from that focus. They present several biological applications, such as acting as drug carriers. Thereby, the goal of this work was the study of conditions to bind anacardic acid (AA) in a dendrimeric derivative with potential action in Chagas disease, which was composed by a central focus of succinic acid (AS) and branches of arginine (Arg) and lysine (Lys). Cruzain, a T. cruzi cysteine protease, is known to catalyze the peptide-binding hydrolysis between lysine and arginine. Synthesis of the solid phase compounds provided the crude derivatives: (1) prodrug AA-KR-NH2 and (2) G.05 AA-K(AS)-R-NH2, which were purified and characterized by High Performance Liquid Chromatography (HPLC) and mass spectrometry. The purified AA-K-R-NH2 and AA-K(AS)-R-NH2 compounds showed yields of 34% and 47%, with purity of 88% and 98% respectively. The results of the enzymatic experiments using AA-K-R-NH2 were not conclusive. It is believed that the low solubility and/or low concentration may have contributed for this. On the chemical stability at pH 7.4 (which simulates blood pH), pH 1.2 (which simulates stomach pH) and pH 8.5 (which simulates intestinal pH), it was observed that AA-K(AS)R-NH2 was stable for 24 hours. These latter results are interesting because the dendrimeric prodrug is expected to reach structurally integral T. cruzi, undergoing hydrolysis and release of the active compound within the parasite

Synthesis of Boronic Acid-functionalized Soluble Dendrimers and Its Application in Detection of Human Liver Microsomal Glycoprotein Based on Enzyme-linked Immunosorbent Assay / 分析化学

The glycoproteins in the biological sample are low abundance and are susceptible to be inhibited and interfered by other non-glycoproteins.An enrichment step is usually required before the glycoprotein analysis, but the operation steps of conventional solid-phase-based glycoprotein enrichment methods are difficult to be compatible with the most classical enzyme-linked immune sorbent assay (ELISA) technique.In this study, a novel water-soluble dendrimer based boronic acid capture (DBC) material was developed using PAMAM 4.0 as the carrier and boronic acid as the affinity group.The method was applied to the detection of glycoproteins in human liver microsomes using ELISA.In this study, the DBC enrichment conditions were optimized by model glycoprotein, and then its sensitivity and anti-interference ability were investigated.This method was applied to the enrichment of glycoproteinsin human liver microsomal.The results showed that the enrichment selectivity of DBC for glycoprotein could be up to 100000 folds, and the enrichment signal of glycoprotein could be increased by 100 times.Therefore, the ELISA method using DBC as a novel enrichment material for glycoprotein had high sensitivity and selectivity in detection of biological samples with only one simple incubation step, which was useful for glycoproteins researches.

Effect of different graft ratios of peg on toxicity in vitro and cellular uptake of PAMAM G5 dendrimers / 中国药学杂志

OBJECTIVE: To study the effect of different graft ratios of PEG on the toxicity in vitro and cellular uptake of PAMAM G5 dendrimers. METHODS: Nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FT-IR) spectroscopy were used to confirm the structure of PEG-PAMAM G5 dendrimers with four different graft ratios. The particle size and Zeta potential of the nanoparticles were determined by nanoparticle size-Zeta potential analyzer. The toxicity in vitro,cellular uptake, and intracellular localization were tested by hemolysis assay,cytotoxicity assay,cellular uptake test,and laser scanning confocal microscope images,respectively. RESULTS: The particle sizes of dendrimers with PEG graft ratios of 7.8%,14.1%, 20.3%,and 24.2% were (17.05 ± 1.77), (20.77 ± 1.02),(21.68 ± 1.04),and (23.19 ± 0.54) nm,respectively. The Zeta potential decreased from (25.57 ± 1.37) mV of PAMAM G5 to (9.27 ± 0.40) mV of PEG31-PAMAM G5. In addition, the hemolytic toxicity and cytotoxicity of PAMAM G5 dendrimers also markedly decreased especially at high concentrations because of PEG modification. Moreover, the PEG-PAMAM G5 dendrimers with particle diameter of nearly 20 nm not only could be taken in by HBMEC cells, but also accumulated in the cell nucleus. CONCLUSION: Modification of PEG can greatly reduce the toxicity of PAMAM G5 dendrimers in vitro, and the higher the degree of modification, the more obvious is the attenuated effect. The PEG-PAMAM G5 dendrimers with particle diameter larger than 20 nm still can be taken in by HBMEC cells and accumulate in the cell nucleus, which provide a foundation for the further research using modified PEG-PAMAM G5 as a basic carrier for genes and nuclear targeting agents in nano medicine.

Dendrimer: a novel approach for drug delivery systems.

Dendrimers are hyper-branched macromolecules having tree like structure, consisting of a core molecule and alternating layers of monomers. So they can be synthesized by divergent and convergent growth methods. During synthesis, properties of dendrimers like dendrimer size, molecular mass, surface group can be controlled and configured to the desired need. Dendrimers have the ability to encapsulate and bind the guest molecule can be used for solubility enhancement, sustained release and various drug delivery applications. The reflections on biomedical and industrial applications of dendrimers given in this report clearly demonstrate the potential the class of polymer architecture and indeed substantiate the high hopes for the future of dendrimers.

Nanoformulations of the vascular inhibitors:combretastatin A4 and combretastatin A4 phosphate / 国际药学研究杂志

Combretastatin A4(CA4),a vascular inhibitor,can target tubulin and inhibit tubulin polymerization,thus it can inhibit the tumor blood vessels and has antitumor effect. But it is insoluble in water and has low bioavailability. CA 4 phosphate (CA4P),the derivative of CA4,can improve the solubility of CA4 and convert into CA4. CA4P is undergoing phaseⅡ/Ⅲclinical tri?als abroad. However,CA4P has several undesirable side effects and relative short half-life in vivo. Nanoformulations can increase the dissolution and absorption of the drug and obtain controlled release and targeting,prolong the efficacy and reduce side effects. Work?ing on the physical and chemical characteristics and biological pharmacy defects of CA4 and CA4P,nanoformulations may change the dissolution,absorption and distribution of the drug. This paper reviews the current nanoformulations of CA4 and CA4P,including den?drimer,polymeric micelle(PM),nanoparticles(NP),long-circulating liposome(LCL),and discusses the prospects of their nanofor?mulations.

Synthesis of barbell-like peptide dendrimer / 国际药学研究杂志

Objective To synthesize barbell-like peptide dendrimer. Methods Through the introduction of small molecule Fmoc-Gly-OH as the linker,NH2-CH2-COO-PEG2000-OOC-CH2-NH2 was obtained efficiently. And then N-α-N-ε-di-Fmoc-L-lysine and N-α-Fmoc-N-ε-Boc-L-lysine were used as branching agents,and barbell-like poly(ethylene glycol)-block-poly(L-lysine)dendrimer with a large number of surface amino groups was synthesized by the liquid-phase peptide synthesis method and divergent approach. Re?sults and Conclusion The structure and relative molecular mass of the final products and intermediates were characterized and con?firmed by 1H NMR and MS. The results revealed that barbell-like peptide dendrimer can be obtained by this method,which lays the foundation of its application in biological areas.

Apoptosis induced by transferring cytosine deaminase suicide gene into kinds of cancer cells with novel polyamidoamine dendrimers / 药学学报

This study demonstrates efficacy of a novel polyamidoamine dendrimers (PAMAM dendrimers) with pentaerythritol derivatives as the core (G5 PD dendrimer) in deliver of the cytosine deaminase (CD) gene and EGFP gene fusion plasmid into different tumor cell lines to induce apoptosis. The physical and chemical properties of G5 PD dendrimers in terms of DNA complexation, particulate properties and transfection efficiencies were investigated and compared with commercial gene vectors PEI 25 kDa. The optimum ratio of G5 PD dendrimer complexed with plasmid DNA was 0.2:1, and the particle size of the complex was (100±5) nm. Compared with the commercial gene carriers PEI, G5 PD dendrimer exhibited a higher transfection efficiency at the weight ratio of 1:1 in three different cell lines, given the fact that PEI are different from PAMAM dendrimers in terms of molecular structure. Furthermore, the cytotoxicity assays of the cell lines transfected with G5 PD dendrimer/pCD-EGFP-N1 followed by exposure to various concentrations of 5-fluorocytosine (5-FC) also showed that the transfected cell lines could generate a very low amount of 5-FC to 5-fluorouracil (5-FU) in a short period of time, which indicating the high expression level of CD gene in the cell line. These results indicate that the CD/5FC system of G5 PD dendrimer has an excellent efficacy in gene delivery.

Nanoformulations of the vascular inhibitors: Combretastatin A4 and combretastatin A4 phosphate / 国际药学研究杂志

Combretastatin A4 (CA4), a vascular inhibitor, can target tubulin and inhibit tubulin polymerization, thus it can inhibit the tumor blood vessels and has antitumor effect. But it is insoluble in water and has low bioavailability. CA4 phosphate (CA4P), the derivative of CA4, can improve the solubility of CA4 and convert into CA4. CA4P is undergoing phase II/III clinical trials abroad. However, CA4P has several undesirable side effects and relative short half-life in vivo. Nanoformulations can increase the dissolution and absorption of the drug and obtain controlled release and targeting, prolong the efficacy and reduce side effects. Working on the physical and chemical characteristics and biological pharmacy defects of CA4 and CA4P nanoformulations may change the dissolution, absorption and distribution of the drug. This paper reviews the current nanoformulations of CA4 and CA4P, including den-drimer, polymeric micelle (PM), nanoparticles (NP), long-circulating liposome (LCL), and discusses the prospects of their nanoformulations.

Synthesis of barbell-like peptide dendrimer / 国际药学研究杂志

Objective To synthesize barbell-like peptide dendrimer. Methods Through the introduction of small molecule Fmoc-Gly-OH as the linker, NH2-CH2-COO-PEG2000-OOC-CH2-NH2 was obtained efficiently. And then N-α-N-ε-di-Fmoc-L-lysine and N-α-Fmoc-N-ε-Boc-L-lysine were used as branching agents, and barbell-like poly(ethylene glycol)-block-poly(L-lysine)dendrimer with a large number of surface amino groups was synthesized by the liquid-phase peptide synthesis method and divergent approach. Results and Conclusion The structure and relative molecular mass of the final products and intermediates were characterized and confirmed by 1H NMR and MS. The results revealed that barbell-like peptide dendrimer can be obtained by this method, which lays the foundation of its application in biological areas.

Antichagásicos e leishmanicidas potenciais: estudo das condições de síntese de pró-fármacos dendriméricos de 3-hidroxiflavona / Potential antichagasic and leishmanicide compounds: study of synthesis conditions of 3-hydroxyflavone dendrimer prodrugs

INTRODUÇÃO: A doença de Chagas e a leishmaniose são doenças tropicais supernegligenciadas, que afetam regiões de extrema pobreza. Os fármacos disponíveis para estas duas doenças são escassos, de eficácia limitada, de alta toxicidade e suscitam casos de resistência. OBJETIVO: Considerando-se a necessidade de desenvolvimento de novos agentes antichagásicos e leishmanicidas, a importância da latenciação no aprimoramento de fármacos/compostos bioativos e a versatilidade de transportadores dendriméricos, o objetivo deste trabalho foi a síntese de pró-fármacos dendriméricos de primeira geração de 3-hidroxiflavona, composto que apresenta potencial atividade tripanomicida e leishmanicida. Desta forma, pretendeu-se obter liberação controlada, melhora da permeabilidade, toxicidade reduzida e aumento da eficácia deste agente bioativo. MATERIAL E MÉTODOS: Para a obtenção desses dendrímeros empregaram-se as abordagens divergente e convergente, compostas por várias etapas de síntese com reações de proteção, desproteção e acoplamentos. RESULTADOS E DISCUSSÃO: A abordagem convergente apresentou problemas sintéticos, devido à instabilidade dos derivados contendo 3-hidroxiflavona nas diferentes condições reacionais e de purificação testadas. No entanto, há indícios da síntese dos pró-fármacos dendriméricos de 3-hidroxiflavona, mas esses compostos apresentam-se impuros. Devido a essa instabilidade e a dificuldade de purificação na abordagem convergente, optou-se pela síntese divergente, no qual o composto bioativo é acoplado na etapa final. Os estudos sintéticos mostraram a obtenção dos intermediários puros formados pelos focos centrais propano- e hexano-diamina acoplados ao ácido málico protegido. CONCLUSÃO: Há indicativos da obtenção de pró-fármacos dendriméricos de 3-hidroxiflavona, ainda que impuros. As maiores dificuldades encontradas foram a purificação e a estabilidade dos compostos obtidos

INTRODUCTION: Chagas' disease and leishmaniasis are super neglected tropical diseases that affect primarily areas of extreme poverty. The drugs available for these diseases are scarce and of limited effectiveness, toxic and rouse resistance. OBJECTIVE: Considering that the development of new antichagasic and leishmanicide agents are urgently needed, the importance of prodrug design to the improvement of drugs and bioactive compounds and the versatility of dendrimers as drug carriers, the objective of this work was the synthesis of dendrimer prodrug of 3-hydroxyflavone, which shows potential antichagasic and leishmanicide activities. Thus, we intended to obtain controlled release, improvement of the permeability, reduction of the toxicity and increase of efficacy of this bioactive agent. MATERIAL AND METHODS: Convergent and divergent approaches have been used to synthesize those compounds. Synthetic steps consist of protection, deprotection and coupling reactions. RESULTS AND DISCUSSION: The convergent approach presented problems due to the instability of the 3-hydroxyflavone derivatives, in different reaction and purification conditions. However, there is evidence of the synthesis of dendrimer prodrugs, though still impure. Due to instability and purification difficulty of intermediate, we performed the divergent synthesis. We obtained the pure intermediates composed by cores propanediamine and hexanediamine coupled to the protected malic acid as spacer group. CONCLUSION: Synthetic studies suggested the synthesis of dendrimer prodrugs, although impure. The greatest difficulties were the purification and the instability of compounds

The polyamidoamine induced mineral deposition on dentin surface in vitro / 实用口腔医学杂志

Objective:To evaluate the sealing ability of the 3.0th generation of polyamidoamine dendrimer(3.0 PAMAM)on hu-man dentinal tubules.Methods:1 6 extracted premolars were cut into 2 mm thick dentin slices to establish sensitive dentin model in vitro.Then 2 samples without any treatment were selected randomly into demineralized dentin group,and the remain 1 4 dentine pills were divided into 2 groups by the random number table(n=7).Samples in the experimental group were treated with 3.0 PAMAM, those in the control group were treated with deionized water.After having immersed in the artificial saliva for 2 and 4 weeks respec-tively,the dentin slices were examined by scanning electron microscope(SEM)and X-ray energy dispersive spectroscopy(EDS). Results:SEM showed that the minerals on the surfaces of the dentine disks in experimental group were formed gradually with the time,the dentinal tubules were blocked 4 weeks after treatment.The minerals on the sample surface in control group were less and the dentinal tubules remained open.EDS results showed that Ca/P(1 .49 ±0.1 6)of mineral deposition in the experimental group was higher than that in the control group (1 .1 8 ±0.20)(P<0.05).Conclusion:The 3.0th generation of PAMAMhas the occlu-ding ability by inducing remineralization on the dentine surface and it may be used in the treatment of dentin hypersensitivity.

A Molecular-Imprinted Sensor for Trace Detection of Gibberellin Based on Ferrocenecarboxylic Acid Multiply Marked Dendrimer / 分析化学

A novel strategy employing dendrimer to multi-label the template molecule to improve the sensitivity of molecularly imprinted electrochemical sensor was proposed. The determination relies on a competition reaction between poly ( diethylene-triaminepenta-acetic acid )-glycol ester ( PDTPA )-ferrocene-carboxylic acid ( FcA ) labeled gibberellins acid 3 ( GA3 ) and GA3 in the sample. Since one cavity corresponds with multiple FcA, instead of only one FcA, the intensity of the detecting signal was greatly enhanced, so was the sensitivity of the sensor. Experimental results showed that the molecularly imprinted electrochemical sensor was sensitive to GA3 detection at a concentration from 2. 0í10-9 to 1. 0í10-7 mol/L, with a detection limit of 9. 3í10-10 mol/L. In addition, the sensor had good reproducibility and its feasibility was verified in the analysis of series of real beer samples.

Application of novel nanoparticles carriers in drug or gene delivery / 中国药学杂志

OBJECTIVE: To summary the application of new types of nanoparticles carriers emerged in recent years in drug or gene delivery. METHODS: By sorting, analyzing and summarizing domestic and foreign literatures, the characteristics, in vivo and in vitro properties and the applications in pharmacy of novel nanoparticles carriers such as nano cochleates, virus-like particles, hydrogel nanoparticles, gold nanoshells, carbon nanomaterials, quantum dots and dendrimers were reviewed and elaborated. RESULTS AND CONCLUSION: Nanoparticles possess special physical and chemical properties which could improve the stability and bioavailability of drugs and have a targeting and sustained release effect.

Nitric oxide releasing-dendrimers: an overview

Platforms able to storage, release or scavenge NO in a controlled and specific manner is interesting for biological applications. Among the possible matrices for these purposes, dendrimers are excellent candidates for that. These molecules have been used as drug delivery systems and exhibit interesting properties, like the possibility to perform chemical modifications on dendrimers surface, the capacity of storage high concentrations of compounds of interest in the same molecule and the ability to improve the solubility and the biocompatibility of the compounds bonded to it. This review emphasizes the recent progress in the development and in the biological applications of different NO-releasing dendrimers and the nitric oxide release pathways in these compounds.

Plataformas capazes de armazenar, liberar ou capturar NO de forma controlada e específica são de grande interesse tendo-se em vista aplicações biológicas. Dentre as possíveis matrizes que podem ser utilizadas para esse fim, os dendrímeros são excelentes candidatos. Essas moléculas têm sido empregadas em sistemas para o transporte de fármacos e apresentam propriedades interessantes tais como a possibilidade de modificações químicas em sua superfície, a capacidade de estocar altas concentrações de compostos de interesse em uma só molécula e a possibilidade de aumentar a solubilidade e a biocompatibilidade dos compostos a eles ligados. Esta revisão enfatiza os recentes avanços no desenvolvimento e nas aplicações biológicas de diferentes dendrímeros liberadores de NO e a forma em que o óxido nítrico é liberado nesses compostos.

Dendritic surface functionalization of nanomaterials: controlling properties and functions for biomedical applications

A wide variety of nanomaterials have demonstrated promise in medical applications such as drug delivery and imaging. In these applications, the surface chemistry of the materials is critical as it plays an important role in determining the toxicity and biodistribution behavior of the material. We review here the functionalization of nanomaterials with dendrons as an efficient method to alter the surface chemistry of the materials, introducing new properties and functions. Described here is the functionalization of superparamagnetic iron oxide nanoparticles (SPIO) with dendritic guanidines to enhance their transport into cells for magnetic resonance imaging applications. The introduction of dendrons bearing peripheral hydroxyls, amines, guanidines, carbohydrates and Gd(III) chelates to polymer vesicles (polymersomes) is also described. These dendritic moieties allow for modulation of toxicity, cell uptake, protein binding, and contrast agent efficiency, while at the same time allowing the stabilities of the polymersomes to be maintained. Thus, this approach holds promise for the development of a wide range of multifunctional materials for pharmaceutical applications.

Uma grande variedade de nanomateriais tem demonstrado aplicações médicas promissoras, tais como liberação de fármacos e em imagens. Nestas aplicações, a superfície química dos materiais é crítica, uma vez que exerce papel importante na determinação da toxicidade e comportamento de biodistribuição do material. Aqui, nós revisamos a funcionalização de nanomateriais, como dendrons, como método eficiente de alterar a superfície química destes compostos, introduzindo novas propriedades e funções. Descritos aqui estão nanopartículas superparamagnéticas de óxido de ferro (do inglês, SPIO), com guanidinas dendríticas para aumentar seu transporte para o interior das células, úteis em imagens de ressonância magnética. A introdução de dendrons contendo hidroxilas, aminas, guanidinas, carboidratos e quelatos de Gd(III) periféricos em vesículas poliméricas (polymersomes) também está descrita. Esses grupos dendríticos permitem a modulação de toxicidade, captura celular, ligação à proteína e eficiência como agente de contraste, enquanto que, ao mesmo tempo, permitem a manutenção da estabilidade das vesículas poliméricas. Assim, essa abordagem é promissora para o desenvolvimento de grande variedade de materiais multifuncionais para aplicações farmacêuticas.