Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery

Abstract

Abstract:Despite the enormous potential of nanomedicine, the search for materials from renewable resources that balance bio-medical requirements and engineering aspects is still challenging. This study proposes an easy method to make nanoparticles composed of oxidized starch and chitosan, both isolated from natural biopolymers. The careful adjustment of C/N ratio, polymer concentration and molecular weight allowed for tuning of particle characteristics. The system's carrier capability was assessed both for anti-infectives and for nucleic acid. Higher starch content polyplexes were found to be suitable for high encapsulation efficiency of cationic anti-infectives and preserving their bactericidal function. A cationic carrier was obtained by coating the anionic polyplex with chitosan. Coating allowed for a minimal amount of cationic polymer to be employed and facilitated plasmid DNA loading both within the particle core and on the surface. Transfection studies showed encouraging result, approximately 5% of A549 cells with reporter gene expression. In summary, starch-chitosan complexes are suitable carriers with promising perspectives for pharmaceutical use.

Kinetics of mRNA delivery and protein translation in dendritic cells using lipid-coated PLGA nanoparticles

“…The toxicity difference at a higher concentration between lipid-PLGA and chitosan-PLGA nanoparticles might be associated with the pH sensitivity of the primary ammonium group in chitosan showing changing deprotonation degree depending on the surrounding pH value in comparison to the quaternary ammonium group in DOTMA. The HBSS-buffer used for the toxicity studies has a pH of 7.4 a value in which chitosan reveals a slight diminishing protonation degree resulting in a decrease of ζ-potential and presumably less cellular interaction [ 31 ]. Additionally to that, the hydrophobic nature of the DOTMA envelope might elicit a better interaction with cells and hence uptake.…”

“…Before TEM-visualization, 10 μL of each NP dispersion was applied on a carbon coated copper grid (type S160-4 from Plano GmbH, Wetzlar, Germany) and the excess solution was removed after 10 min incubation time. In order to improve the contrast of the TEM-images, adhered NPs on the copper grid were in another experimental setting further stained with 0.5% (w/v) phosphotungstic acid solution (PTA; Sigma-Aldrich, Darmstadt, Germany) according to our previous studies described in Yasar et al [ 31 ]. For SEM visualization, the copper grid with applied NPs were then placed onto a carbon disc and gold-sputtered.…”

“…mRNA-mCherry (CleanCap™ mCherry mRNA (5moU); TriLink BioTechnologies LLC, CA, USA) was loaded at different ratios to both LPNs and CS-PLGA NPs to evaluate their potential as efficient mRNA delivery systems. Thus, the anionic mRNA was loaded onto the surface of both cationic NPs (following our previous protocol described in Yasar et al [ 31 ]) using mRNA:NPs weight ratios of 1:10, 1:20 and 1:30. A volume of 1 μg/μL mRNA-mCherry was mixed with an appropriate amount of each NPs and further incubated at room temperature for 1 h. This carried out in mRNA complexed NPs (mRNA:LPNs and mRNA:CS-PLGA NPs).…”

Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform

“…The positively charged colistin contains a lipophilic moiety and could interact with aSq molecules via both charged and hydrophobic interactions (Yasar et al, 2018;Menina et al, 2019). We, thus, hypothesized that the solvent evaporation method could enhance the LC and EE of colistin in aSq-NPs.…”

Itaconic Acid Increases the Efficacy of Tobramycin against Pseudomonas aeruginosa Biofilms

“…These antibiotics, however, cannot entirely eradicate bacteria embedded in biofilms and mucus [ 1 , 7 ]. To combat this kind of bacterial resistance, most recent research has mainly aimed to propose more potent agents [ 8 ], combinations of agents [ 6 , 8 ], or better delivery methods [ 9 , 10 , 11 , 12 ], which could have a prolonged and high enough bioavailability at the site of action and especially inside the biofilms by crossing and/or weakening this biological barrier. Notably, the co-administration of an antibiotic and a pathoblocker (e.g., quorum sensing inhibitor (QSI) which is not supposed to kill bacteria but affect biofilm formation) has shown advantages over antibiotic monotherapy and is a promising strategy to overcome the growing resistance problem in pulmonary PA infections [ 11 , 13 , 14 , 15 ] Biofilm penetrating nanoparticles based on self-assembled squalenyl hydrogen sulfate enabled the simultaneous co-delivery of hydrophobic QSI and hydrophilic tobramycin (Tob), leading to a significantly enhanced (~16-fold) efficacy of Tob to eradicate PA biofilms [ 11 ].…”