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The reversed intra- and extracellular pH in tumors as a unified strategy to chemotherapeutic delivery using targeted nanocarriers

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Acta pharmaceutica Sinica B 2021年第8期11卷 2243-2264页

作者： edgar pérez-herrero Alberto Fernández-Medarde Departamento de Ingeniería Química y Tecnología Farmacéutica Universidad de La LagunaLa Laguna 38206TenerifeSpain Instituto Universitario de Bio-Orgánica Antonio González Universidad de La LagunaLa Laguna 38206TenerifeSpain Instituto Universitario de Tecnologías Biomédicas Universidad de La LagunaLa Laguna 38200TenerifeSpain Instituto de Biología Molecular y Celular Del Cáncer Centro de Investigación Del Cáncer(USAL-CSIC)Salamanca 37007Spain

Solid tumors are complex entities,comprising a wide variety of malignancies with very different molecular *** this,they share a set of characteristics known as"hallmarks of cancer"that can be used as common therapeutic ***,every tumor needs to change its metabolism in order to obtain the energy levels required for its high proliferative rates,and these adaptations lead to alterations in extra-and intracellular *** changes in p H are common to all solid tumors,and can be used either as therapeutic targets,blocking the cell proton transporters and reversing the pH changes,or as means to specifically deliver anticancer *** this review we will describe how proton transport inhibitors in association with nanocarriers have been designed to block the pH changes that are needed for cancer cells to survive after their metabolic *** will also describe studies aiming to decrease intracellular pH in cancer using nanoparticles as molecular cages for protons which will be released upon UV or IR light ***,we will comment on several studies that have used the extracellular pH in cancer for an enhanced cell internalization and tumor penetration of nanocarriers and a controlled drug delivery,describing how nanocarriers are being used to increase drug stability and specificity.

关键词： pH-Gradient inversion Metabolism of glucose proton transport inhibitors proton-caged carriers Chemotherapy Targeted drug delivery pH-Sensitive nanocarriers Warburg effect Cancer

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New injectable two-step forming hydrogel for delivery of bioactive substances in tissue regeneration

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Regenerative Biomaterials 2019年第3期6卷 149-162页

作者： edgar pe´rez-herrero patricia Garcı´a-Garcı´a Jaime Go´mez-Morales Matias Llabre´s Araceli Delgado Carmen E´vora Department of Chemical Engineering and pharmaceutical Technology University of La LagunaLa Laguna 38200TenerifeSpain Institute of Biomedical Technologies(ITB) Center for Biomedical Research of the Canary Islands(CIBICAN)University of La LagunaLa Laguna 38071TenerifeSpain Laboratory of Crystallographic Studies Andalusian Earth Sciences InstituteSpanish Research Council—University of GranadaArmillaGranada 18100Spain Institute of Tropical Diseases and Healthcare of the Canary Islands University of La LagunaLa Laguna 38203TenerifeSpain

A hydrogel based on chitosan,collagen,hydroxypropyl-c-cyclodextrin and polyethylene glycol was developed and *** incorporation of nano-hydroxyapatite and pre-encapsulated hydrophobic/hydrophilic model drugs diminished the porosity of hydrogel from 81.6262.25%to 69.9863.07%.Interactions between components of hydrogel,demonstrated by FTIR spectroscopy and rheology,generated a network that was able to trap bioactive components and delay the burst *** thixotropic behavior of hydrogel provided adaptability to facilitate its implantation in a minimally invasive *** profiles from microspheres included or not in hydrogel revealed a two-phase behavior with a burst-and a controlled-release *** same release rate for microspheres included or not in the hydrogel in the controlled-release period demonstrated that mass transfer process was controlled by internal *** diffusion coefficients,Deff,that describe internal diffusion inside microspheres,and mass transfer coefficients,h,*** contribution of hydrogel to mass transfer,were determined using‘genetic algorithms’,obtaining values between 2.64·10^(-15) and 6.67·10^(-15)m^(2)/s for Deff and 8.50·10^(-10) to 3.04·10^(-9) m/s for *** proposed model fits experimental data,obtaining an R2-value ranged between 95.41 and 98.87%.In vitro culture of mesenchymal stem cells in hydrogel showed no manifestations of intolerance or toxicity,observing an intense proliferation of the cells after 7 days,being most of the scaffold surface occupied by living cells.

关键词： hydrogel collagen–cyclodextrin–chitosan rheology mass transfer estradiol FITC-dextran

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Understanding the Glycoproteins Release from Alginate-Barium Capsules in physiologic Enviroments

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Advances in Chemical Engineering and Science 2011年第4期1卷 256-270页

作者： edgar perez herrero Eva M. Martin del Valle Miguel A. Galán Department of Chemical Engineering University of Salamanca

The authors carried out a steady and unsteady mass transfer studies to simulate both the release of proteins in physiologic environments and proteins transport through a tissue or organ from polymeric capsules by using a substance, the rhodamine B isothiocyanate dextran (RBID) that mimics the behaviour of glycoproteins such as vascular endothelial growth factor (VEFG). These studies highlighted the importance of electrostatic interactions between alginate and proteins in the release processes. Thereby, this fact has opened new perspectives in order to use these kind of capsules in protein recognition processes. The electrostatic interactions between alginate and RBID allow pH-dependent controlled release systems that simulate the behaviour of glycoproteins.

关键词： Controlled Release Systems proteins Glycoproteins Growth Factors Mass Transfer Unsteady Steady

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