Polyglutamic Acid-Gated Mesoporous Silica Nanoparticles for Enzyme-Controlled Drug Delivery

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.langmuir.6b01715.Mesoporous silica nanoparticles (MSNs) are highly attractive as supports in the design of controlled delivery systems that can act as containers for the encapsulation of therapeutic agents, overcoming common issues such as poor water solubility and poor stability of some drugs and also enhancing their bioavailability. In this context, we describe herein the development of polyglutamic acid (PGA)-capped MSNs that can selectively deliver rhodamine B and doxorubicin. PGA-capped MSNs remain closed in an aqueous environment, yet they are able to deliver the cargo in the presence of pronase because of the hydrolysis of the peptide bonds in PGA. The prepared solids released less than 20% of the cargo in 1 day in water, whereas they were able to reach 90% of the maximum release of the entrapped guest in ca. 5 h in the presence of pronase. Studies of the PGA-capped nanoparticles with SK-BR-3 breast cancer cells were also undertaken. Rhodamine-loaded nanoparticles were not toxic, whereas doxorubicin-loaded nanoparticles were able to efficiently kill more than 90% of the cancer cells at a concentration of 100 μg/mL.A.T. wishes to express her gratitude to the Erasmus mundus (Svagata.eu) financial support. A.U. and C. de la T. are grateful to the Spanish Ministry of Education, Culture and Sport for her doctoral fellowship. We thank the Spanish Government (Project MAT2015-64139-C4-1-R, MINECO/FEDER) and Generalitat Valenciana (Project PROMETEOII/2014/047) for their support. The authors also thank UPV electron microscopy services for the technical support.Tukappa, A.; Ultimo, A.; De La Torre Paredes, C.; Pardo Vicente, MT.; Sancenón Galarza, F.; Martínez-Máñez, R. (2016). Polyglutamic Acid-Gated Mesoporous Silica Nanoparticles for Enzyme-Controlled Drug Delivery. Langmuir. 32(33):8507-8515. https://doi.org/10.1021/acs.langmuir.6b01715S85078515323

Acetylcholinesterase-capped Mesoporous Silica Nanoparticles Controlled by the Presence of Inhibitors

[EN] Two different acetylcholinesterase (AChE)-capped mesoporous silica nanoparticles (MSNs), S1-AChE and S2-AChE, were prepared and characterized. MSNs were loaded with rhodamine B and the external surface was functionalized with either pyridostigmine derivative P1 (to yield solid S1) or neostigmine derivative P2 (to obtain S2). The final capped materials were obtained by coordinating grafted P1 or P2 with AChE ' s active sites (to give S1-AChE and S2-AChE, respectively). Both materials were able to release rho-damine B in the presence of diisopropylfluorophosphate (DFP) or neostigmine in a concentration-dependent manner via the competitive displacement of AChE through DFP and neostigmine coordination with the AChE ' s active sites. The responses of S1-AChE and S2-AChE were also tested with other enzyme inhibitors and substrates. These studies suggest that S1-AChE nanoparticles can be used for the selective detection of nerve agent simulant DFP and paraoxon.Financial support from the Spanish Government and FEDER funds (Project MAT2015‐64139‐C4‐1‐R, AGL2015‐70235‐C2‐2‐R) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. Ll. P. is grateful to the Universitat Politécnica de Valencia for his grant.Pascual, L.; El Sayed Shehata Nasr, S.; Marcos Martínez, MD.; Martínez-Máñez, R.; Sancenón Galarza, F. (2017). Acetylcholinesterase-capped Mesoporous Silica Nanoparticles Controlled by the Presence of Inhibitors. Chemistry - An Asian Journal. 12(7):775-784. https://doi.org/10.1002/asia.201700031S775784127Alberti, S., Soler-Illia, G. J. A. A., & Azzaroni, O. (2015). Gated supramolecular chemistry in hybrid mesoporous silica nanoarchitectures: controlled delivery and molecular transport in response to chemical, physical and biological stimuli. 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Pharmacognostical Evaluation and Comparative Phytochemical Screening of Rumex vesicarius L.

Pharmacognosy is a simple and reliable tool by which complete information of the crude drug can be obtained. Therefore in this context the detailed pharmacognostic study of various parts like leaf, stem, and root of Rumex vesicarius L. has been carried out with the aim to establish its pharmacognostical standards. The parameters selected were physicochemical, fluorescence analysis and preliminary phytochemical screening along with mineral analysis. In physico-chemical evaluation the ash values and extractive values were studied.. The powder of Rumex vesicarius.L was successively extracted with petroleum ether, chloroform, methanol and water by both cold maceration and hot soxhlet extraction for the identification of the best solvent and method. Preliminary phytochemical screening was carried out for all the extracts.  Fluorescence analysis performed showed the wide range of fluorescence colours for the crude powder. The preliminary phytochemical screening shows maximum chemical constituents in the different extract obtained from cold maceration of different plant parts compared to extract obtained from hot soxhlet extraction.  The principal constituents of Rumex vesicarius L. include phenols, tannins, flavonoids, saponins, triterpenoids, alkaloids, anthraquinones, quinines, reducing sugars, proteins, lipids and carbohydrates. The inorganic elementary analysis performed revealed the presence of sodium, chloride and iron. The present study indicates the  pharmacognostical and physicochemical characteristics and preliminary properties of the different parts of Rumex vesicarius.L for the identification of the drug in the dry form. Thus plays a crucial role in standardization of crude drug

Pharmacognostical Evaluation and Comparative Phytochemical Screening of Rumex vesicarius L.

Pharmacognosy is a simple and reliable tool by which complete information of the crude drug can be obtained. Therefore in this context the detailed pharmacognostic study of various parts like leaf, stem, and root of Rumex vesicarius L. has been carried out with the aim to establish its pharmacognostical standards. The parameters selected were physicochemical, fluorescence analysis and preliminary phytochemical screening along with mineral analysis. In physico-chemical evaluation the ash values and extractive values were studied.. The powder of Rumex vesicarius.L was successively extracted with petroleum ether, chloroform, methanol and water by both cold maceration and hot soxhlet extraction for the identification of the best solvent and method. Preliminary phytochemical screening was carried out for all the extracts.  Fluorescence analysis performed showed the wide range of fluorescence colours for the crude powder. The preliminary phytochemical screening shows maximum chemical constituents in the different extract obtained from cold maceration of different plant parts compared to extract obtained from hot soxhlet extraction.  The principal constituents of Rumex vesicarius L. include phenols, tannins, flavonoids, saponins, triterpenoids, alkaloids, anthraquinones, quinines, reducing sugars, proteins, lipids and carbohydrates. The inorganic elementary analysis performed revealed the presence of sodium, chloride and iron. The present study indicates the  pharmacognostical and physicochemical characteristics and preliminary properties of the different parts of Rumex vesicarius.L for the identification of the drug in the dry form. Thus plays a crucial role in standardization of crude drug

Cytotoxicity and hepatoprotective attributes of methanolic extract of Rumex vesicarius L.

BACKGROUND: To evaluate the hepatoprotective potential and invitro cytotoxicity studies of whole plant methanol extract of Rumex vesicarius L. Methanol extract at a dose of 100 mg/kg bw and 200 mg/kg bw were assessed for its hepatoprotective potential against CCl4-induced hepatotoxicity by monitoring activity levels of SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamic pyruvic transaminase), ALP (Alkaline phosphatase), TP (Total protein), TB (Total bilirubin) and SOD (Superoxide dismutase), CAT (Catalase), MDA (Malondialdehyde). The cytotoxicity of the same extract on HepG2 cell lines were also assessed using MTT assay method at the concentration of 62.5, 125, 250, 500 μg/ml. RESULTS: Pretreatment of animals with whole plant methanol extracts of Rumex vesicarius L. significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver. The biochemical parameters in serum also improved in treated groups compared to the control and standard (silymarin) groups. Histopathological investigation further corroborated these biochemical observations. The cytotoxicity results indicated that the plant extract which were inhibitory to the proliferation of HepG2 cell line with IC50 value of 563.33 ± 0.8 Mg/ml were not cytotoxic and appears to be safe. CONCLUSIONS: Rumex vesicarius L. whole plant methanol extract exhibit hepatoprotective activity. However the cytotoxicity in HepG2 is inexplicable and warrants further study