scholarly journals An Underestimated Factor: The Extent of Cross-Reactions Modifying APIs in Surface-Modified Liposomal Preparations Caused by Comprised Activated Lipids

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4436
Author(s):  
Max Sauter ◽  
Jürgen Burhenne ◽  
Walter E. Haefeli ◽  
Philipp Uhl

Despite the nowadays available plentitude of strategies to selectively introduce functional surface modification of liposomes, in preclinical research this process is still primarily performed after liposomal preparation utilizing comprised activated phospholipids with functionalized head groups. However, because these activated lipids are present during the liposomal preparation process, they can cross-react with incorporated drugs, especially the particularly often utilized active esters and maleimide groups. Macromolecular drugs, being composed of amino acids, are particularly prone to such cross-reactions due to their often multiple reactive functionalities such as amino and disulfide groups. To demonstrate this impact on the formulation in liposomal surface modification, we assessed the extent of cross-reaction during the liposomal preparation of two activated phospholipids with typically used head group functionalized phospholipids, with the two peptide drugs vancomycin and insulin comprising disulfide and amino functionalities. Both drugs revealed a considerable fraction of covalent modification (estimated 2 to 12%) generated during the liposome preparation process with comprised activated lipids. Modification of the active pharmaceutical ingredients (APIs) was determined by high-resolution mass spectrometric analysis. These findings clearly demonstrate the non-negligibility of potential cross reactions using the post preparation liposomal surface modification strategy in preclinical research.

2017 ◽  
Vol 139 (6) ◽  
Author(s):  
X. P. Zhu ◽  
P. C. Du ◽  
Y. Meng ◽  
M. K. Lei ◽  
D. M. Guo

Inverse problem of manufacturing is studied under a framework of high performance manufacturing of components with functional surface layer, where controllable generation of surface integrity is emphasized due to its pivotal role determining final performance. Surface modification techniques capable of controlling surface integrity are utilized to verify such a framework of manufacturing, by which the surface integrity desired for a high performance can be more effectively achieved as reducing the material and geometry constraints of manufacturing otherwise unobtainable during conventional machining processes. Here, thermal spraying of WC–Ni coatings is employed to coat stainless steel components for water-lubricated wear applications, on which a strategy for direct problem from process to performance is implemented with surface integrity adjustable through spray angle and inert N2 shielding. Subsequently, multiple surface integrity parameters can be evaluated to identify the major ones responsible for wear performance by elucidating the wear mechanism, involving surface features (coating porosity and WC phase retention) and surface characteristics (microhardness, elastic modulus, and toughness). The surface features predominantly determine tribological behaviors of coatings in combination with the surface characteristics that are intrinsically associated with the surface features. Consequently, the spray process with improved N2 shielding is designed according to the desired surface integrity parameters for higher wear resistance. It is demonstrated that the correlations from processes to performance could be fully understood and established via controllable surface integrity, facilitating solution to inverse problem of manufacturing, i.e., realization of a material and geometry integrated manufacturing.


2012 ◽  
Vol 529-530 ◽  
pp. 161-166
Author(s):  
Toshiisa Konishi ◽  
Minori Mizumoto ◽  
Michiyo Honda ◽  
Mamoru Aizawa

We have previously developed hydroxyapatite (HAp) cement based on the chelate-setting mechanism of sodium inositol hexaphosphate (IP6), in which HAp powder was prepared by surface-modification with IP6 after ball-milling of the HAp powder (conventional process). Meanwhile, we have recently established novel powder preparation process (modified process). In the present study, the adsorption behavior of IP6 on the surface of HAp at both the processes was circumstantially examined to clarify the chelating mechanism of IP6. The adsorbed amount of IP6 increased with the IP6 concentration in both the processes; however, the adsorbed amount of IP6 at the modified process was lower than that at the conventional process. X-ray photoelectron spectroscopic study revealed that the IP6 adsorbed on the surface of HAp powders. The degree in dispersion of the HAp particles at the modified process was higher than that at conventional process. Furthermore, the elution of IP6 from the powders prepared at the novel process was lower than that of the powders at the conventional process.


The Analyst ◽  
2014 ◽  
Vol 139 (9) ◽  
pp. 2108 ◽  
Author(s):  
Abby J. Schadock-Hewitt ◽  
Jennifer J. Pittman ◽  
Kenneth A. Christensen ◽  
R. Kenneth Marcus

2015 ◽  
Vol 3 (4) ◽  
pp. 629-634 ◽  
Author(s):  
Xinhong Xiong ◽  
Zhaoqiang Wu ◽  
Jingjing Pan ◽  
Lulu Xue ◽  
Yajun Xu ◽  
...  

We have demonstrated a simple and effective approach for the functional surface modification of poly(dimethylsiloxane) (PDMS) via visible light-induced grafting polymerization at room temperature.


2011 ◽  
Vol 152 ◽  
pp. e109-e111
Author(s):  
Liming Yang ◽  
Yilei Shi ◽  
Jie Chen ◽  
Liang Rong ◽  
Wei Yang

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 428
Author(s):  
Marianne Zaruba ◽  
Lena Roschitz ◽  
Haider Sami ◽  
Manfred Ogris ◽  
Wilhelm Gerner ◽  
...  

Extracellular vesicles produced by different types of cells have recently attracted great attention, not only for their role in physiology and pathology, but also because of the emerging applications in gene therapy, vaccine production and diagnostics. Less well known than their eukaryotic counterpart, also bacteria produce extracellular vesicles, in the case of the Gram-negative E. coli the main species is termed outer membrane vesicles (OMVs). In this study, we show for the first time the functional surface modification of E. coli OMVs with glycosylphosphatidylinositol (GPI)-anchored protein, exploiting a process variably described as molecular painting or protein engineering in eukaryotic membranes, whereby the lipid part of the GPI anchor inserts in cell membranes. By transferring the process to bacterial vesicles, we can generate a hybrid of perfectly eukaryotic proteins (in terms of folding and post-translational modifications) on a prokaryotic platform. We could demonstrate that two different GPI proteins can be displayed on the same OMV. In addition to fluorescent marker proteins, cytokines, growth factors and antigens canb be potentially transferred, generating a versatile modular platform for a novel vaccine strategy.


2017 ◽  
Vol 524 ◽  
pp. 389-399 ◽  
Author(s):  
Zhong Ma ◽  
Xiaolong Lu ◽  
Chunrui Wu ◽  
Qijun Gao ◽  
Lihua Zhao ◽  
...  

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