Stearylated cycloarginine nanosystems for intracellular delivery - simulations, formulation and proof of concept

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00469474" target="_blank" >RIV/61388963:_____/16:00469474 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1039/c6ra16432c" target="_blank" >http://dx.doi.org/10.1039/c6ra16432c</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c6ra16432c" target="_blank" >10.1039/c6ra16432c</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Stearylated cycloarginine nanosystems for intracellular delivery - simulations, formulation and proof of concept

Popis výsledku v původním jazyce

Cationization of nanocarriers has been sought after as a viable strategy to surmount cellular barriers that impede intracellular drug and gene delivery. A plethora of cationic compounds including both lipids and polymers have been designed and developed for efficient cellular penetration. The toxicity of these cationic agents, however, precludes their use in drug delivery. Conjugation with biomolecules like sugars and amino acids to produce novel cationic agents is being investigated to generate biocompatible molecules to achieve safe drug delivery. In this study, we propose to mitigate the toxicity of stearylamine, a cationic lipid, by tethering it to arginine, to yield a novel cationic ligand. Ligand loaded liposomes and nanoparticles were fabricated and evaluated for their surface charge and cellular uptake. Furthermore, molecular dynamics simulations were utilized as a tool to understand the accessibility of the novel ligand and stearylamine loaded liposomal systems. This paper presents the one pot synthesis of a novel stearylated arginine dipeptide and its incorporation in delivery systems along with its in vitro and in vivo toxicity evaluation.

Název v anglickém jazyce

Stearylated cycloarginine nanosystems for intracellular delivery - simulations, formulation and proof of concept

Popis výsledku anglicky

Cationization of nanocarriers has been sought after as a viable strategy to surmount cellular barriers that impede intracellular drug and gene delivery. A plethora of cationic compounds including both lipids and polymers have been designed and developed for efficient cellular penetration. The toxicity of these cationic agents, however, precludes their use in drug delivery. Conjugation with biomolecules like sugars and amino acids to produce novel cationic agents is being investigated to generate biocompatible molecules to achieve safe drug delivery. In this study, we propose to mitigate the toxicity of stearylamine, a cationic lipid, by tethering it to arginine, to yield a novel cationic ligand. Ligand loaded liposomes and nanoparticles were fabricated and evaluated for their surface charge and cellular uptake. Furthermore, molecular dynamics simulations were utilized as a tool to understand the accessibility of the novel ligand and stearylamine loaded liposomal systems. This paper presents the one pot synthesis of a novel stearylated arginine dipeptide and its incorporation in delivery systems along with its in vitro and in vivo toxicity evaluation.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

—

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

RSC Advances

ISSN

2046-2069

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

114

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

113538-113550

Kód UT WoS článku

000389905300093

EID výsledku v databázi Scopus

2-s2.0-85002427129