Intracellular sorting of differently charged chitosan derivatives and chitosan-based nanoparticles

Zubareva, A. A.; Lyalina, Tatiana; Варламов, В. П.; Svirshchevskaya, E. V.

doi:10.1039/c5nr00327j

Cited by 27 publications

(18 citation statements)

References 54 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chitosan-coated particles were taken up better than particles without chitosan, proving that the cationic surface may improve the intracellular uptake. The former particles also showed stronger accumulation in lysosomes as observed by LysoTracker reda cationic fluorescent dye that accumulates in acidic compartments as an indicator of lysosomal content, a behavior also described by others (43). While the lysosomal degradation of PLGA nanocarriers remains to be investigated in more detail, the co-localization with lysosomes is at least likely to enhance drug release and polymer degradation (30), also contributing to the safe elimination of such nanocarriers.…”

Section: Discussionsupporting

confidence: 66%

PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus

Dimer

Carvalho-Wodarz

Goes

et al. 2020

Nanomedicine: Nanotechnology, Biology and Medicine

View full text Add to dashboard Cite

Drug delivery systems are promising for targeting antibiotics directly to infected tissues. To reach intracellular Staphylococcus aureus and Mycobacterium abscessus, we encapsulated clarithromycin in PLGA nanocapsules, suitable for aerosol delivery by nebulization of an aqueous dispersion. Compared to the same dose of free clarithromycin, nanoencapsulation reduced 1,000 times the number of intracellular S. aureus in vitro. In RAW cells, while untreated S. aureus was located in acidic compartments, the treated ones were mostly situated in nonacidic compartments. Clarithromycin-nanocapsules were also effective against M. abscessus (70-80% killing efficacy). The activity of clarithromycin-nanocapsules against S. aureus was also confirmed in vivo, using a murine wound model as well as in zebrafish. The permeability of clarithromycin-nanocapsules across Calu-3 monolayers increased in comparison to the free drug, suggesting an improved delivery to sub-epithelial tissues. Thus, clarithromycin-nanocapsules are a promising strategy to target intracellular S. aureus and M. abscessus.

show abstract

Section: Discussionsupporting

confidence: 66%

PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus

Dimer

Carvalho-Wodarz

Goes

et al. 2020

Nanomedicine: Nanotechnology, Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…32 Earlier, we have shown that positively charged C and Cbased NPs poorly penetrated epithelial cells and were engulfed mostly by macrophages. 33 At the same time, negatively charged succinylchitosan and corresponding NPs easily penetrated all types of cells and were transported into lysosomal compartment. Based on our earlier results and the results obtained in this study, it can be hypothesized that CP via cytosolic pathway is effective for positively charged molecules.…”

Section: In Vivo Effect Of L-based Npsmentioning

confidence: 98%

Cross-presentation of lactoferrin encapsulated into chitosan-based nanoparticles

et al. 2016

View full text Add to dashboard Cite

Induction of CD8+ cytotoxic T-cell response is essential for the protection from intracellular pathogens. It requires major histocompatibility complex class I processing of newly synthesized proteins transported from the cytosolic pathway. Presentation of mature soluble proteins occurs via a cross-presentation (CP) pathway that is much less efficient in the activation of cytotoxic response. Encapsulation of proteins into polymeric nanoparticles (NPs) can modulate the efficacy of antigen CP. In this article, a model antigen lactoferrin (L) was encapsulated into polysaccharide NPs with different physicochemical properties (size, charge, and hydrophobicity) and used as an immunogen. CD8+ or CD4+ associated IgG2a or IgG1 subclasses of L-specific antibodies, respectively, served as a measure of CD8+ versus CD4+ T-cell activation. Among five types of NPs produced, only succinylchitosan–galactomannan (LSG) and succinylchitosan–PEG-chitosan (LSPC) NPs induced a significant IgG2a response. IgG1 production was comparable in all but hydrophobic succinyl-dodecyl-chitosan (LSD) NPs, where it was only marginal. Confocal studies demonstrated that galactomannan-equipped LSG-NPs induced vacuolar type of CP, while positively charged LSPC-NPs were transported mostly via the cytosolic CP pathway.

show abstract

“…Further, Zubareva et al. [ 100 ] investigated the influence of the surface charge of ChNPs on their fate and cellular uptake by MIAPaCa‐2 cells and RAW264.7 cells. To this end, positively charged ChNPs, composed of hexanoyl chitosan (HCh), and negatively charged ChNPs made of succinoyl chitosan (SCh), were generated.…”

Section: Cellular Uptake Studies and Drug Delivery Systemsmentioning

confidence: 99%

Biomedical and Pharmacological Uses of Fluorescein Isothiocyanate Chitosan‐Based Nanocarriers

Caprifico

Polycarpou

Foot

et al. 2020

Macromolecular Bioscience

View full text Add to dashboard Cite

with a DDA ranging between 70% and 85% becomes soluble in dilute acidic solutions such as acetic acid or formic acid. [1] Indeed, the primary amino groups of chitosan have a pK a of ≈6.5 so that, following protonation, they confer upon chitosan the feature of solubility in weakly acidic aqueous solution, allowing the polymer to be easily manipulated. [3] The DDA of chitosan plays a key role in determining its physicochemical properties, which are affected by the proportion of free amino groups (-NH 2) remaining on the polymeric chain upon deacetylation. Both the primary amino and secondary hydroxyl groups behave as reactive functional groups on chitosan. Indeed, these groups allow chitosan to be susceptible to chemical modifications such as acylation, tosylation, quaternization, alkylation, and O-carboxymethylation. [4] As a result, the chitosan structure can be functionalized and optimized to improve drug loading or release. [5] Chitosan-based nanocarriers (ChNCs), including nanoparticles (NPs), micelles, or polyplexes, have received significant attention for their numerous advantageous features such as natural sourcing, biodegradability, easy functionalizations, and low toxicity. [6] The mucoadhesive property of chitosan is key for drug delivery purposes. [7] Indeed, chitosan is a positively charged polymer that can form electrostatic bonds with the negatively charged mucous layer, made of mucin glycoproteins that cover the epithelial cells of the mucosa. The establishment of these bonds allows drug-loaded ChNCs to exhibit higher absorption and retention times at the target, while reducing dosing frequency. [8] Furthermore, chitosan is used as permeation enhancer since increases the uptake of the drugs through a transient and reversible opening of the tight junctions (TJs) protecting the paracellular pathway between endothelial cells in the so-called blood-brain barrier (BBB). [9] This is due to F-actin depolymerization and leakage of the TJ protein zonula occludens-1. [7] The small size and large surface area of NCs allow their passage through biological membranes, such the BBB, and accumulation at the intracellular (such as lysosomes) or intranuclear (DNA or RNA) target site. [10] ChNCs are distinctive for their ability to protect the encapsulated therapeutic agent and improve its bioavailability by altering the pharmacokinetics. [10] The endocytic mechanisms responsible for the internalization of ChNCs as a drug delivery system may differ according to the cell type and the drug to be delivered. Numerous biological and pharmacological properties characterize chitosan. These include antitumor, antifungal, antioxidant, immunoenhancing, and wound healing properties. [11] Furthermore, chitosan is Chitosan-based nanocarriers (ChNCs) are considered suitable drug carriers due to their ability to encapsulate a variety of drugs and cross biological barriers to deliver the cargo to their target site. Fluorescein isothiocyanatelabeled chitosan-based NCs (FITC@ChNCs) are used extensively in biomedical and pharmacological...

show abstract

Intracellular sorting of differently charged chitosan derivatives and chitosan-based nanoparticles

Cited by 27 publications

References 54 publications

PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus

PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus

Cross-presentation of lactoferrin encapsulated into chitosan-based nanoparticles

Biomedical and Pharmacological Uses of Fluorescein Isothiocyanate Chitosan‐Based Nanocarriers

Contact Info

Product

Resources

About