Hollow microcapsule with pH-sensitive chitosan/polymer shell for in vitro delivery of curcumin and gemcitabine

Abstract Glutamine synthetase (GS) in the liver is expressed in a small perivenous, highly specialized hepatocyte population and is essential for the maintenance of low, non-toxic ammonia levels in the organism. However, GS activity can be impaired by tyrosine nitration of the enzyme in response to oxidative/nitrosative stress in a pH-sensitive way. The underlying molecular mechanism as investigated by combined molecular simulations and in vitro experiments indicates that tyrosine nitration can lead to a fully reversible and pH-sensitive regulation of protein function. This approach was also used to understand the functional consequences of several recently described point mutations of human GS with clinical relevance and to suggest an approach to restore impaired GS activity.

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A pH-sensitive curcumin loaded microemulsion-filled alginate and porous starch composite gels: Characterization, in vitro release kinetics and biological activity

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2021.05.174 ◽

2021 ◽

Author(s):

Ying-Hui Li ◽

Yu-Sheng Wang ◽

Jing-Song Zhao ◽

Zi-Yan Li ◽

Hai-Hua Chen

Keyword(s):

Biological Activity ◽

Release Kinetics ◽

In Vitro Release ◽

Ph Sensitive ◽

Composite Gels ◽

Vitro Release

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Synthesis and In Vitro Assessment of pH-Sensitive Human Serum Albumin Conjugates of Pirarubicin

Pharmaceuticals ◽

10.3390/ph14010022 ◽

2020 ◽

Vol 14 (1) ◽

pp. 22

Author(s):

Kenji Tsukigawa ◽

Shuhei Imoto ◽

Keishi Yamasaki ◽

Koji Nishi ◽

Toshihiko Tsutsumi ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Coupling Reaction ◽

Synthetic Polymer ◽

Ph Sensitive ◽

Acidic Ph ◽

Polymer Conjugate ◽

Acidic Conditions

In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development.

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A Hybrid Coil/Polymer Device for Occlusion of Cerebral Aneurysms

Journal of Medical Devices ◽

10.1115/1.4000203 ◽

2009 ◽

Vol 3 (4) ◽

Cited By ~ 1

Author(s):

Fangmin Xu ◽

Kevin Hart ◽

Claire E. Flanagan ◽

John C. Nacker ◽

Roham Moftakhar ◽

...

Keyword(s):

Cerebral Aneurysms ◽

In Vitro Models ◽

In Vivo Studies ◽

Polymer Shell ◽

Device Implantation ◽

Occlusion Device ◽

Aneurysm Occlusion ◽

Aneurysm Model

The treatment of cerebral aneurysms is frequently accomplished via endovascular delivery of metal coils in order to occlude the aneurysm and prevent rupture. This procedure involves imprecise packing of large lengths of wire into the aneurysm and often results in high rates of aneurysm recanalization. Over time, this incomplete aneurysm occlusion can lead to aneurysm enlargement, which may have fatal consequences. This report describes the fabrication and preliminary testing of a novel aneurysm occlusion device composed of a single metal coil surrounded by a biocompatible polymer shell. These coil-in-shell devices were tested under flow conditions in synthetic in vitro models of saccular aneurysms and deployed in vivo in a short-term porcine aneurysm model to study occlusion efficacy. A single nickel titanium shape memory wire was used to deploy a biocompatible, elastic polymeric shell, leading to aneurysmal sac filling in both in vitro and in vivo aneurysm models. The deployment of this coil-in-shell device in synthetic aneurysm models in vitro resulted in varying degrees of aneurysm occlusion, with less than 2% of trials resulting in significant leakage of fluid into the aneurysm. Meanwhile, in vivo coil-in-shell device implantation in a porcine aneurysm model provided proof-of-concept for successful occlusion, as both aneurysms were completely occluded by the devices. Both in vitro and in vivo studies demonstrated that this coil-in-shell device may be attractive as an alternative to traditional coil embolization methods in some cases, allowing for a more precise and controlled aneurysm occlusion.

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Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding

The Journal of Cell Biology ◽

10.1083/jcb.200804161 ◽

2008 ◽

Vol 183 (5) ◽

pp. 865-879 ◽

Cited By ~ 122

Author(s):

Christian Frantz ◽

Gabriela Barreiro ◽

Laura Dominguez ◽

Xiaoming Chen ◽

Robert Eddy ◽

...

Keyword(s):

Actin Filament ◽

Structural Changes ◽

Ph Sensor ◽

Ph Sensitive ◽

Actin Binding ◽

Filamentous Actin ◽

Filament Dynamics ◽

Ph Dependent ◽

Dynamics Simulations

Newly generated actin free barbed ends at the front of motile cells provide sites for actin filament assembly driving membrane protrusion. Growth factors induce a rapid biphasic increase in actin free barbed ends, and we found both phases absent in fibroblasts lacking H+ efflux by the Na-H exchanger NHE1. The first phase is restored by expression of mutant cofilin-H133A but not unphosphorylated cofilin-S3A. Constant pH molecular dynamics simulations and nuclear magnetic resonance (NMR) reveal pH-sensitive structural changes in the cofilin C-terminal filamentous actin binding site dependent on His133. However, cofilin-H133A retains pH-sensitive changes in NMR spectra and severing activity in vitro, which suggests that it has a more complex behavior in cells. Cofilin activity is inhibited by phosphoinositide binding, and we found that phosphoinositide binding is pH-dependent for wild-type cofilin, with decreased binding at a higher pH. In contrast, phosphoinositide binding by cofilin-H133A is attenuated and pH insensitive. These data suggest a molecular mechanism whereby cofilin acts as a pH sensor to mediate a pH-dependent actin filament dynamics.

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Synthesis and Antimicrobial Properties of Highly Cross-Linked pH-Sensitive Hydrogels through Gamma Radiation

Polymers ◽

10.3390/polym13142223 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2223

Author(s):

Moises Bustamante-Torres ◽

Victor H. Pino-Ramos ◽

David Romero-Fierro ◽

Sandra P. Hidalgo-Bonilla ◽

Héctor Magaña ◽

...

Keyword(s):

Bacterial Infections ◽

Antimicrobial Agents ◽

Film Formation ◽

Antimicrobial Properties ◽

Ph Sensitive ◽

Scanning Calorimetry ◽

Polymeric Systems ◽

E Coli ◽

High Prevalence

The design of new polymeric systems for antimicrobial drug release focused on medical/surgical procedures is of great interest in the biomedical area due to the high prevalence of bacterial infections in patients with wounds or burns. For this reason, in this work, we present a new design of pH-sensitive hydrogels copolymerized by a graft polymerization method (gamma rays), intended for localized prophylactic release of ciprofloxacin and silver nanoparticles (AgNPs) for potential topical bacterial infections. The synthesized hydrogels were copolymerized from acrylic acid (AAc) and agar. Cross-linked hydrogel film formation depended on monomer concentrations and the degree of radiation used (Cobalt-60). The obtained hydrogel films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and mechanical testing. The swelling of the hydrogels was evidenced by the influence of their pH-sensitiveness. The hydrogel was loaded with antimicrobial agents (AgNPs or ciprofloxacin), and their related activity was evaluated. Finally, the antimicrobial activity of biocidal-loaded hydrogel was tested against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) on in vitro conditions.

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