Impact of PEG Chain Length on the Physical Properties and Bioactivity of PEGylated Chitosan/siRNA Nanoparticles in Vitro and in Vivo

2017 ◽  
Vol 9 (14) ◽  
pp. 12203-12216 ◽  
Author(s):  
Chuanxu Yang ◽  
Shan Gao ◽  
Frederik Dagnæs-Hansen ◽  
Maria Jakobsen ◽  
Jørgen Kjems
2021 ◽  
Vol 7 (6) ◽  
pp. eaba2458
Author(s):  
Weier Bao ◽  
Falin Tian ◽  
Chengliang Lyu ◽  
Bin Liu ◽  
Bin Li ◽  
...  

The poor understanding of the complex multistep process taken by nanocarriers during the delivery process limits the delivery efficiencies and further hinders the translation of these systems into medicine. Here, we describe a series of six self-assembled nanocarrier types with systematically altered physical properties including size, shape, and rigidity, as well as both in vitro and in vivo analyses of their performance in blood circulation, tumor penetration, cancer cell uptake, and anticancer efficacy. We also developed both data and simulation-based models for understanding the influence of physical properties, both individually and considered together, on each delivery step and overall delivery process. Thus, beyond finding that nanocarriers that are simultaneously endowed with tubular shape, short length, and low rigidity outperformed the other types, we now have a suit of theoretical models that can predict how nanocarrier properties will individually and collectively perform in the multistep delivery of anticancer therapies.


1981 ◽  
Vol 59 (5) ◽  
pp. 640-648 ◽  
Author(s):  
G. R. Lister ◽  
B. W. Thair

The epicuticular leaf wax of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) was recrystallized from chloroform solution in vitro. The striated, tubular forms were reconstituted in sizes which included that observed in vivo, indicating that the final dimensions and morphology of the wax crystals are functions of physical properties of the component molecules, rather than an enzyme-dependent polymerization. Subsequent evaluation of all observations and data formed the basis for the scale construction of a model of the tubular wax crystal.


2006 ◽  
Vol 6 (2) ◽  
pp. 328-336 ◽  
Author(s):  
Kariona A. Grabińska ◽  
Paula Magnelli ◽  
Phillips W. Robbins

ABSTRACT Chs4p (Cal2/Csd4/Skt5) was identified as a protein factor physically interacting with Chs3p, the catalytic subunit of chitin synthase III (CSIII), and is indispensable for its enzymatic activity in vivo. Chs4p contains a putative farnesyl attachment site at the C-terminal end (CVIM motif) conserved in Chs4p of Saccharomyces cerevisiae and other fungi. Several previous reports questioned the role of Chs4p prenylation in chitin biosynthesis. In this study we reinvestigated the function of Chs4p prenylation. We provide evidence that Chs4p is farnesylated by showing that purified Chs4p is recognized by anti-farnesyl antibody and is a substrate for farnesyl transferase (FTase) in vitro and that inactivation of FTase increases the amount of unmodified Chs4p in yeast cells. We demonstrate that abolition of Chs4p prenylation causes a ∼60% decrease in CSIII activity, which is correlated with a ∼30% decrease in chitin content and with increased resistance to the chitin binding compound calcofluor white. Furthermore, we show that lack of Chs4p prenylation decreases the average chain length of the chitin polymer. Prenylation of Chs4p, however, is not a factor that mediates plasma membrane association of the protein. Our results provide evidence that the prenyl moiety attached to Chs4p is a factor modulating the activity of CSIII both in vivo and in vitro.


2013 ◽  
Vol 79 (12) ◽  
pp. 3813-3821 ◽  
Author(s):  
Jo-Ann Chuah ◽  
Satoshi Tomizawa ◽  
Miwa Yamada ◽  
Takeharu Tsuge ◽  
Yoshiharu Doi ◽  
...  

ABSTRACTSaturation point mutagenesis was carried out at position 479 in the polyhydroxyalkanoate (PHA) synthase fromChromobacteriumsp. strain USM2 (PhaCCs) with specificities for short-chain-length (SCL) [(R)-3-hydroxybutyrate (3HB) and (R)-3-hydroxyvalerate (3HV)] and medium-chain-length (MCL) [(R)-3-hydroxyhexanoate (3HHx)] monomers in an effort to enhance the specificity of the enzyme for 3HHx. A maximum 4-fold increase in 3HHx incorporation and a 1.6-fold increase in PHA biosynthesis, more than the wild-type synthase, was achieved using selected mutant synthases. These increases were subsequently correlated with improved synthase activity and increased preference of PhaCCsfor 3HHx monomers. We found that substitutions with uncharged residues were beneficial, as they resulted in enhanced PHA production and/or 3HHx incorporation. Further analysis led to postulations that the size and geometry of the substrate-binding pocket are determinants of PHA accumulation, 3HHx fraction, and chain length specificity.In vitroactivities for polymerization of 3HV and 3HHx monomers were consistent within vivosubstrate specificities. Ultimately, the preference shown by wild-type and mutant synthases for either SCL (C4and C5) or MCL (C6) substrates substantiates the fundamental classification of PHA synthases.


2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Eun-Su Lim ◽  
Young-Bae Park ◽  
Young-Sun Kwon ◽  
Won-Jun Shon ◽  
Kwang-Won Lee ◽  
...  

2020 ◽  
Author(s):  
Jiho Lee ◽  
Sung Park

Abstract BackgroundThis study presents a novel technique to develop an equivalent circuit model (ECM) for analyzing the responses of the layered body structure to transcutaneous electrical nerve stimulation (TENS) by parameterizing electrical and geometrical properties. Many classical ECMs use custom meta-parameters instead of the physically driven parameters because of the difficulty in projecting physical properties directly into ECM. However, the difference in what parameters are customized hampers general agreement in modeling the responses to TENS. To overcome this limitation, we propose a tissue property-based (TPB) approach for the direct parameterization of the layered body structure.ResultsThe proposed method was first validated through in vitro phantom studies and then was applied in-vivo to analyze the TENS on the forearm. The TPB-ECM calculated the impedance network in the forearm and corresponding the responses to TENS. In addition, the modeled impedance was in good agreement with well-known impedance properties that have been achieved empirically.ConclusionsThe TPB approach uses the physical parameters instead of meta-parameters, thus overcoming the disagreement problem of conventional ECMs. Therefore, the TPB-ECM has a potential for widely-applicable TENS analysis and could provide impactful guidance in the TENS parameter design.


2021 ◽  
Vol 10 (3) ◽  
pp. 2825-2831
Author(s):  
Rijawan Rajjak Pathan

Pellets formulation with natural gums. The formulation of an enzyme as well as pH dependant pellets containing natural gums such as Mornings oleifera gum Lam. (MOG) and Cyamopsis tetragonolobus gum Taub. (CTG) were used for enzyme dependant release and further coating is provided to shows colon-specific delivery. Extrusion and spheronization techniques were used for the preparation of pellets. Pellets of budesonide evaluated for various properties such as flow behavior, physical properties such as sphericity, roundness, aspect ratio, hardness, and friability also investigated in vitro and in vivo targeting in rabbit. Preparation of pellets was done by using extrusion and spheronization method with the use of optimized concentration of gums those were 7.5% and 10% for CTG and MOG respectively and proportion of solvent mixture of water and Isopropyl alcohol in the ratio of 80:20. Pellets of budesonide evaluated for various properties includes flow behavior, physical properties such as sphericity, roundness, aspect ratio, hardness, and friability and found that all properties as per official limit also in vitro release study found that release of uncoated pellets in a sustained manner in 0.1N HCl for 2h due to swelling of natural gum, therefore further step of the coating was done in fluidized bed coater to prevent the release of drug in the upper part of GIT and after coating found that In vitro release of drug at the colonic environment and it confirmed with in vivo investigation in rabbit with X-ray examination of targeting and found that pellets reach at colonic part without disintegration. The use of natural gums for preparation of pellets in optimized concentration and wetting agent produce a formulation with all required chemical and physical properties and it gives effective in vitro release and also shows In vivo targeting in rabbit and due to use of natural gum for preparation of pellets also reduce some problems of metabolism of synthetic excipients.


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