The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-

Monomethoxy poly(ethylene glycol)-

Synthesis, characterization, and in vitro evaluation of gamma radiationinduced PEGylated isoniazid

Background: The search for innovative anti-tubercular agents has received increasing attention in tuberculosis chemotherapy because Mycobacterium tuberculosis infection has steadily increased over the years. This underlines the necessity for new methods of preparation for polymer-drug adducts to treat this important infectious disease. The use of poly(ethylene glycol)(PEG) is an alternative producing anti-tubercular derivatives. However, it is not yet known whether PEGylated isonicotinylhydrazide conjugates obtained by direct links with PEG are useful for therapeutic applications. Results: Here, we synthesized a PEGylated isoniazid (PEG-g-INH or PEG­INH) by gamma radiation-induced polymerization, for the first time. The new prodrugs were characterized using Raman and UV/Vis spectrometry. The mechanism of PEGylated INH synthesis was proposed. The in vitro evaluation of a PEGylated isonicotinylhydrazide macromolecular prodrug was also carried out. The results indicated that PEG­INH inhibited the bacterial growth above 95% as compared with INH, which showed a lower value (80%) at a concentration of 0.25 µM. Similar trends are observed for 0.1, 1, and 5 µM. Conclusions: In summary, the research suggests that it is possible to covalently attach the PEG onto INH by the proposed method and to obtain a slow-acting isoniazid derivative with little toxicity in vitro and higher antimycobacterial potency than the neat drug.

PLA/PGA and its co-Polymers in Alveolar Bone Regeneration. A Systematic Review / PLA/PGA y sus Copolímeros en Regeneración Ósea Alveolar. Una Revisión Sistemática

ABSTRACT: The aim of this research was to perform a systematic review to identify the most frequent uses of PLA/ PGA in alveolar bone regeneration and their results. A study was designed to answer the question: What are the most frequent uses of PLA/PLGA and their copolymers in alveolar bone regeneration?. A systematic search was done on MEDLINE, EMBASE and LILACS from April 1993 to December 2017. The search string used on MEDLINE was: (((polylactic acid) OR PLA) OR PLA-based copolymers) OR PLA blends) OR PLA scaffolds)) AND ((("Bone Regeneration"[Mesh]) OR bone regeneration) OR guided bone regeneration). The search was complemented by a manual review of the references from the articles included. Most of the studies selected were weak and, regarding the most frequent uses of PLA/PGA, 13 studies used it as a resorbable membrane, two as an absorbable mesh, one as an absorbable screw and three as filling material. Based on our results, the authors consider that PLA/PGA requires a delicate relation between the mechanical resistance and the degradation process. PLA/PGA does not interrupt bone regeneration; however, the influence in cellular events related to bone regeneration and later osseointegration have not been identified.

RESUMEN: El objetivo de esta revisión fue realizar una revisión sistemática de la literatura para identificar los usos más frecuentes de PLA/PGA en regeneración ósea en área maxilofacial y sus resultados. Se diseñó un estudio para responder a la pregunta: ¿Cuáles son los usos más frecuentes de PLA/PLGA y sus copolímeros en regeneración ósea en el sector maxilofacial?. Los estudios seleccionados fueron en su mayoría débiles y sobre los usos más frecuentes de PLA/PGA, 13 estudios lo utilizaron como membrana reabsorbible, 2 estudios como malla absorbible, un estudio como tornillo absorbible y 3 estudios como material de relleno. En base a nuestros resultados, los autores estiman que PLA/PGA requiere una delicada relación entre la resistencia mecánica que ofrece y la degradación que se produce; PLA/ PGA no interrumpe la regeneración ósea, sin embargo, no se ha identificado la potencialidad o influencia que presenta en los eventos celulares de la regeneración y posterior oseointegración.

Construction of controllable polyethylene glycol bioactive coating with hemocompatibility from the surface of modified glass substrate / 生物医学工程学杂志

A diblock copolymer, poly(ethylene glycol) methacrylate-block-glycidyl methacrylate (PEGMA-GMA), was prepared on glass substrate by surface-initiated atom transfer radical polymerization (SI-ATRP), and endothelial specific peptide Arg-Glu-Asp-Val (REDV) was immobilized at the end of the PEGMA-GMA polymer brush by ring opening reaction through the rich epoxy groups in the GMA. The structure and hydrophilicity of the polymer brushes were characterized by static water contact angle, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The results showed that the REDV modified copolymer brushes were successfully constructed on the glass substrates. The REDV peptide immobilized onto surface was quantitatively characterized by ultraviolet-visible spectroscopy (UV-VIS). The blood compatibility of the coating was characterized by recalcification time and platelet adhesion assay. The results showed that the polymer coating had good blood compatibility. The multifunctional active polymer coating with PEGMA and peptide produced an excellent prospect in surface construction with endothelial cells selectivity.

Controlled delivery of ibuprofen from poly(vinyl alcohol)-poly (ethylene glycol) interpenetrating polymeric network hydrogels / 药物分析学报

Hydrogels composed of poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG) were synthesized using glutaraldehyde as crosslinker and investigated for controlled delivery of the common anti-inflammatory drug, ibuprofen (IBF). To regulate the drug delivery, solid inclusion complexes (ICs) of IBF in β–cyclodextrin (β–CD) were prepared and added to the hydrogels. The ICs were prepared by the microwave irradiation method, which is more environmentally benign. The formation of IC was confirmed by various analytical techniques and the synthesized hydrogels were also characterized. Controlled release of drug was achieved from the hydrogels containing the ICs in comparison to the rapid release from hydrogels containing free IBF. The preliminary kinetic analysis emphasized the crucial role of β–CD in the drug release process that in-fluences the polymer relaxation, thereby leading to prolonged release. The cytotoxicity assay validated the hydrogels as non-toxic in nature and hence can be utilized for controlled delivery of IBF.

Celastrol-loaded macrophage membrane camouflaged PEG-PLGA nano-particles for targeted therapy of severe acute pancreatitis in rats / 药学学报

Severe acute pancreatitis (SAP) is characterized by both local and systemic inflammatory responses. This study was designed to develop a site-specific delivery strategy for SAP therapy using celastrol (CLT). First, murine RAW264.7 cells were used as a model of macrophage cell line, cell membranes were obtained by emptying intracellular contents via hypotonic lysing, mechanical membrane disruption, and differential centrifugation. Poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs) were then prepared by sonication. With the collected membrane materials, macrophage membrane coated PEG-PLGA NPs (RNPs) were then prepared by extrusion through a 400 nm polycarbonate membrane. Biodistribution study in rats with SAP showed RNPs selectively accumulated in the inflamed pancreatic tissues. Compared with CLT loaded NPs, CLT loaded RNPs were proven to effectively attenuate local pancreatic inflammation and systemic inflammation in rats with SAP.

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.

Preparation and quality evaluation of comet-shaped hydroxy camptothecin-loaded amphiphilic block copolymer / 药学学报

In this study, we used Shirasu porous glass membrane (SPG) as a template and hydroxy camptothecin (HCPT) as a model drug to prepare the comet-shaped MePEG[methoxyl poly(ethylene glycol)]-PLGA[poly(lactic-co-glycolic acid)-HCPT amphiphilic block copolymer. Our method was optimized by the orthogonal design method. The partical size, zeta potential, drug-loaded content, yield, shape and status of the obtained comet-shaped MePEG-PLGA-HCPT particles were further characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM)/transmission electron microscopy (TEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) et al, respectively. In vitro release was preliminary evaluated. MTT assay to preliminary evaluate the cytotoxicity of particles against human liver BEL-7402 cells. Based on these experimental results, the optimal preparation conditions contain:weight ratio of HCPT to MePEG-PLGA was 1:1, nitrogen pressure was 100 kPa and SPG membrane pore size was 1.1 μm. The particles exhibited a comet-shaped shape, fairly uniform size and were well dispersed. The drug-loading content was 46.2%, with yield of 96.4%, and zeta -31.4 mV. The distribution of HCPT in particles was very uniform, and HCPT showed a amorphous state existed in particles. The release behavior in vitro showed sustained releasing,and with the drug loading content in proportion to the release of the drug. MTT test indicated that the HCPT-loaded comet-shaped particles had enhanced the cytotoxicity against human liver BEL-7402 cells relatively to the HCPT-loaded spherical particles in vitro. The results showed a promising potential application of the preparation in clinical treatment of tumor.

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.

Validation of high performance liquid chromatography method for determination of meloxicam loaded PEGylated nanocapsules

abstract A method to ensure that an analytical method will produce reliable and interpretable information about the sample must first be validated, making sure that the results can be trusted and traced. In this study, we propose to validate an analytical high performance liquid chromatography (HPLC) method for the quantitation of meloxicam loaded PEGylated nanocapsules(M-PEGNC). We performed a validation study, evaluated parameters including specificity, linearity, quantification limit, detection limit, accuracy, precision and robustness. PEGylated nanocapsules were prepared by interfacial deposition of preformed polymer, and the particle size, polydispersity index, zeta potential, pH value and encapsulation efficiency were characterized. The proposed HPLC method provides selective, linear results in the range of 1.0-40.0 μg/mL; quantification and detection limits were 1.78 μg/mL and 0.59 μg/mL, respectively; relative standard deviation for repeatability was 1.35% and intermediate precision was 0.41% and 0.61% for analyst 1 and analyst 2, respectively; accuracy between 99.23 and 101.79%; robustness between 97.13 and 98.45% for the quantification of M-PEGNC. Mean particle diameters were 261 ± 13 nm and 249 ± 20 nm, polydispersity index was 0.15 ± 0.07 and 0.17 ± 0.06, pH values were 5.0 ± 0.2 and 5.2 ± 0.1, and zeta-potential values were -37.9 ± 3.2 mV e -31.8 ± 2.8 mV for M-PEGNC and placebo(B-PEGNC), respectively. In conclusion, the proposed analytical method is suitable for the quality control of M-PEGNC. Moreover, suspensions showed monomodal size distributions and low polydispersity index indicating high homogeneity of formulations with narrow size distributions, and appropriate pH and zeta potential. The extraction process was efficient for release of meloxicam from nanostructured systems.

resumo Para se assegurar que um método analítico produzirá informação confiável e interpretável sobre a amostra este deve ser inicialmente validado, tornando claro que os resultados podem ser confiados e rastreados. Neste estudo, propomos validar um método de cromatografia líquida de alta eficiência (CLAE) para a quantificação do meloxicam encapsulado em nanocápsulas PEGuiladas (M-PEGNC). Efetuamos a validação, avaliando parâmetros de especificidade, linearidade, limite de quantificação, limite de detecção, exatidão, precisão e robustez. As nanocápsulas PEGuiladas foram preparadas por deposição interfacial do polímero pré-formado e caracterizaram-se o tamanho da partícula, índice de polidispersão, potencial zeta, pH e eficiência de encapsulação. O método de CLAE proposto fornece resultados seletivos e lineares na faixa de 1,0-40,0 mg/mL; limites de quantificação e detecção de 1,78 mg/mL e 0,59 mg/mL, respectivamente; desvio padrão relativo para a repetibilidade de 1,35% e precisão intermediária de 0,41% e 0,61% para o analista 1 e analista 2, respectivamente; exatidão entre 99,23 e 101,79%; robustez entre 97,13 e 98,45% para a quantificação de M-PEGNC. Os diâmetros médios das partículas foram 261 ± 13 nm e 249 ± 20 nm; índice de polidispersão de 0,15 ± 0,07 e 0,17 ± 0,06, valores de pH de 5,0 ± 0,2 e 5,2 ± 0,1 e valores do potencial zeta de -37,9 ± 3,2 mV e -31,8 ± 2,8 mV para o M-PEGNC e o placebo(B-PEGNC), respectivamente. Concluindo, o método analítico proposto é adequado para o controle de qualidade do M-PEGNC. Além disso, suspensões mostraram distribuição de tamanho monomodal e baixo índice de polidispersão, indicando alta homogeneidade das formulações com distribuição estreita de tamanho, pH e potencial zeta apropriados. O processo de extração foi eficiente para a liberação do meloxicam dos sistemas nanoestruturados.

Research on PEGylated uricase by periodate oxidation and reductive- amination / 中国药科大学学报

@#PEGylated uricase was prepared with the N-terminal amino site-specific modification by periodate oxidation followed by reductive-amination. A monomethoxy poly(ethylene glycol)intermediate was synthesized by amidation from monomethoxy poly(ethylene glycol)amine hydrochloride 20000(mPEG20000-NH2 ·HCl)with the relative molecular mass of 20 kD and N-(tert-butoxycarbonyl)-L-serine(Boc-Ser-OH), and then the Boc group of the intermediate was removed by trifluoroacetic acid(TFA)to produce the desired product Ser-mPEG20000. This compound could be oxidated by periodate to obtain a new poly(ethylene glycol)aldehyde derivative with high activity, which could be used to modify proteins with the N-terminal amino site-specific PEGylation after ultrafiltration, and the modification conditions to uricase by Ser-mPEG20000 were optimized. The structures of poly(ethylene glycol)intermediate and the target product were characterized by IR and 1H NMR, and the overall yield of the target product was 72. 8%. The preliminary modification to uricase indicated that the desired product Ser-mPEG20000 could modify proteins easily and efficiently. The optimal modification conditions of uricase PEGylated by Ser-mPEG20000 were obtained as follows: the molar ratio of Ser-mPEG20000 to uricase was 2 ∶1; the pH value of solution was 5. 0; the reaction temperature was 25 °C and the reaction time was 6 h.

Cholesterol modified PEG-P Asp (DET)/miRNA complex: Preparation, physicochemical properties, and cellular uptake / 第二军医大学学报

Objective To synthesize PEG-P[Asp(DET)] with 10% cholesterol chloroformate modified on its side chain and to study the physicochemical properties and cellular uptake of polymer complex PEG-P[Asp(DET)]-chole/hsa-miR-15a. Methods PEG-P[Asp(DET)] was synthesized by ring opening polymerization and modification with cholesterol chloroformate to acquire hydrophobicity, and MRI was used to verify its structure. The particle size, Zeta potential, stability, encapsulation efficiency, and cytotoxicity of the polymer complex PEG-P[Asp(DET)]-10% chole/hsa-miR-15a were examined. Finally, in vitro cellular uptake experiment was carried out with the leukemia cell line K562. Results The synthesized polymer PEG-P[Asp(DET)]-10% chole had fine solubility and could form into stable polymer complex PEG-P[Asp(DET)]-chole/hsa-miR-15a. When nitrogen-phosphorus ratio (N/P) was at 20 and concentration of the miRNA was 5 μmol/mL, the particle size was (192. 4±10. 8) nm, Zeta potencial was (6. 9±0. 9) mV, andencapsulation efficiency was (90. 5±3. 2)%. The complex displayed good stability under experimental condition. In vitrr cellular uptake experimental indicated that the uptake capacity of PEG-P[Asp(DET)]-10%chole/hsa-miR-15a was higher than that of the commercial agent lipo2000. Conclusion PEG-P[Asp (DET)]-10%chole is a fine gene polymer carrier for miRNA and can achieve stable cellular uptake of miRNA.

Biochemical and molecular analysis of sugarcane genotypes response to salinity and drought.

Sugarcane genotypes such as tolerant (Co 99004), and sensitive (Co 97010) were subjected to NaCl (170 and 250mM) and Poly ethylene glycol (-0.8Mpa and -1.7Mpa) treatment and evaluated through biochemical and molecular analysis to assess the commonness between salinity and drought stress. Among the biochemical characters analyzed total chlorophyll decreased and proline, lipid peroxidase, xanthophylls increased with severe stress (both salinity and drought). Peroxidase and superoxide dismutase activity increased with isozymes showing over expression under stress condition. In Reverse Transcriptase-PCR the genes p5cs and ADC1 showed differential amplification with tolerant genotypes recording up-regulation. The results showed that the tolerant genotype (Co 99004) expressed better stability under the saline and water stress conditions where as the sensitive genotype (97010) failed to perform under the stress conditions.

Synthesis and MALDI-ToF characterization of dendronized poly(ethylene glycol)s

Well-defined hybrids of linear poly(ethylene glycol)s (PEGs) and dendritic polyesters were prepared via the dendronization of the alcohol end groups of the mono and difunctional linear PEGs. Though useful for rudimentary product characterization, GPC and NMR could not verify the overall structural purity of these linear-dendritic hybrids. On the other hand, the detailed data provided by MALDI-ToF mass spectrometry enabled confirmation of the high structural purity of the dendronized PEGs at each step of the dendronization procedure. The well-defined number of functionalities on these dendronized PEGs, renders them particularly useful for research in the biomedical sphere where functionality and purity are of the utmost importance. The MALDI-ToF mass spectrometric approach described herein represents a valuable technique for detailed monitoring of these dendronization reactions, as well as a variety of other polymer end group modifications.

Híbridos bem definidos de poli(etilenoglicol) lineares (PEGs) e poliésteres dendriméricos foram preparados via "dendronização" de álcool e grupos de PEGs lineares mono e bifuncionais. Embora úteis para a caracterização rudimentar de produtos, Cromatografia por Permeação em Gel e RMN podem não demonstrar a pureza estrutural global desses híbridos lineares dendríticos. Por outro lado, informações detalhadas provenientes de espectrometria de massas MALDI-ToF permitiram a confirmação de elevada pureza estrutural de PEGs "dendronizados" em cada passo do processo de "dendronização". O número de funcionalidades bem definidas destes PEGs "dendronizados", torna-os particularmente úteis para pesquisa na área biomédica, na qual funcionalidade e pureza são de grande importância. A abordagem de espectrometria de massas MALDI-ToF descrita aqui representa uma técnica valiosa para o monitoramento detalhado destas reações de "dendronização", bem como diversas modificações de outros polímeros e grupos.

Effect of Poly Ethylene GlycolPEGGraft Polymerization onto Polymethy lmethacrylatePMMAon Cultured Keratocyte Adhesion

In this study, the effect of surface modification of polymethylmethacry-late[PMMA]by grafting of poly[ethylene glycol][PEG]on cell adhesion was investigated. PMMA surface was treated with ozone and then PEG-acry-late[PEGA]was graft-polymerized. Ozone treatment of the surface was car-ried out at room temperature by applying constant flow of oxygen[4.5liter/min]and 1 bar pressure. After ozone treatment, PMMA was immersed immediately in 20 wt%aq. PEG-acrylate solutions in glass ampoules. After degassing, the ampoule was sealed and kept at 60 degrees C for 24 hours to complete the graft polymerization. PMMA surface grafted with PEG revealed the enhanced oxygen content at ESCA analysis and the decreased dynamic receding contact angles. The adhesion of keratocytes onto modified PMMA was investigated. Keratocytes[4 x105cells/milliliter ]were layered on each PMMA discs which were glued to the bottom of 24-well culture plates, and cultured in a CO2 incubator for 24 hours. The adherent cells onto the surfaces were harvested by trypsinization and counted. The mean numbers of keratocytes on untreated PMMA, PEG-grafted PMMA with 1hour ozone treatment and PEG-grafted PMMA with 2 hour were 72.5 x104 and 6.5 x104 and 7.6 x104cells respectively, and there was a significant statistical difference [p=0.002], irrespective of ozone treatment period. This result suggests that surface modification of PMMA using PEG grafting may reduce etroprosthetic membrane formation of artificial cornea.

The separation of baicalin by aqueous two-phase extraction system / 中成药

AIM:To explore the extraction mechanism of the separation-purification of baicalin in aqueous two-phase systems. METHODS:By experiment,nonionic surfactant PEG-K_2PHO_4-H_2O two aqueous phase system was selected to phase-forming conditions,and the effect of temperature,pH,salt composition on partition of baicalin PEG/salt system. RESULTS:The extraction rate of baicalin in aqueous two-phase system was up to 98.6%. CONCLUSION:The two aqueous phase system for baicalin extraction is easy to operate has good reproductivity,and can be applied in mass production.