Efficacy assessment of self-assembled PLGA-PEG-PLGA nanoparticles: Correlation of nano-bio interface interactions, biodistribution, internalization and gene expression studies

Dimchevska, Simona; Geškovski, Nikola; Koliqi, Rozafa; Matevska-Geskovska, Nadica; Vallejo, Vanessa Gómez; Szczupak, Bogusław; Sebastián, Eneko San; Llop, Jordi; Hristov, Delyan R.; Monopoli, Marco P.; Petruševski, Gjorgji; Ugarković, Sonja; Dimovski, Aleksandar; Goračinova, Katerina

doi:10.1016/j.ijpharm.2017.05.054

Cited by 29 publications

(30 citation statements)

References 50 publications

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“…12) PLGA membranes and PLGA nanoparticles (PLGA NPs) have been widely studied in the pharmaceutical and medical fields as particulate materials. [13][14][15] PLGA NPs is one of the best defined biomaterials available for drug delivery with respect to design and performance as a biodegradable micro/nano-device. 16,17) A recent study demonstrated that the combined use of an anti-tumor molecule and anti-inflammatory molecule showed inhibition of tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Biodegradable PLGA-Nanoparticles Used for pH-Sensitive Intracellular Delivery of an Anti-inflammatory Bacterial Toxin to Macrophages

Harada

Tsutsuki

Zhang

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

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Poly(D,L-lactide-co-glycolic) acid (PLGA) is a synthetic copolymer that has been used to design micro/ nanoparticles as a carrier for macromolecules, such as protein and nucleic acids, that can be internalized by the endocytosis pathway. However, it is difficult to control the intracellular delivery to target organelles. Here we report an intracellular delivery system of nanoparticles modified with bacterial cytotoxins to the endoplasmic reticulum (ER) and anti-inflammatory activity of the nanoparticles. Subtilase cytotoxin (SubAB) is a bacterial toxin in certain enterohemorrhagic Escherichia coli (EHEC) strains that cleaves the host ER chaperone BiP and suppresses nuclear factor-kappaB (NF-κB) activation and nitric oxide (NO) generation in macrophages at sub-lethal concentration. PLGA-nanoparticles were modified with oligo histidine-tagged (6 His-tagged) recombinant SubAB (SubAB-PLGA) through a pH-sensitive linkage, and their translocation to the ER in macrophage cell line J774.1 cells, effects on inducible NO synthase (iNOS), and levels of tumor necrosis factor (TNF)-α cytokine induced by lipopolysaccharide (LPS) were examined. Compared with free SubAB, SubAB-PLGA was significantly effective in BiP cleavage and the induction of the ER stress marker C/EBP homologous protein (CHOP) in J774.1 cells. Furthermore, SubAB-PLGA attenuated LPS-stimulated induction of iNOS and TNF-α. Our findings provide useful information for protein delivery to macrophages and may encourage therapeutic applications of nanoparticles to the treatment of inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Preparation of Biodegradable PLGA-Nanoparticles Used for pH-Sensitive Intracellular Delivery of an Anti-inflammatory Bacterial Toxin to Macrophages

Harada

Tsutsuki

Zhang

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Most of them are of interest for research because they are being developed for a variety of diagnostic and therapeutic applications. 14,60,[112][113][114][115][116][117][118][119] These can be polystyrene (PS) with and without surface modications, polyethylene glycol (PEG), polylactide-derivatives (PLGA), resins, crosslinked cellulose, carbon beads or polylactic acid (PLA). The same holds true for the separately listed group of chitosan particles.…”

Section: Particles Used For Corona Studiesmentioning

confidence: 99%

Isolation methods for particle protein corona complexes from protein-rich matrices

et al. 2020

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“…3 Encapsulating SN-38 in a polymer nanoparticle (PNP) takes advantage of the EPR effect to target drug delivery toward tumour tissues. 1,[4][5][6][7][8][9][10][11][12][13] Amphiphilic block copolymers spontaneously form micellar PNPs with a hydrophilic external corona and a hydrophobic internal core. The SN-38 can be contained within the water-dispersible PNPs, which travel to target tissues through the circulatory system.…”

Section: Introductionmentioning

confidence: 99%

“…The SN-38 can be contained within the water-dispersible PNPs, which travel to target tissues through the circulatory system. Various polymer types have been researched to optimize delivery, including those with hydrophobic blocks comprised of poly(lactic-co-glycolic acid) D r a f t 4 (PLGA), 12 polygluamate (PGlu), [4][5][6] and poly(ε-caprolactone) (PCL). 8,11,13 Poly(ε-caprolactone)b-poly(ethylene oxide) (PCL-b-PEO) is a commonly applied amphiphilic block copolymer in drug delivery investigations, due to the biodegradable and biocompatible nature of its component blocks.…”

Section: Introductionmentioning

confidence: 99%

“…crystallinity,19 it does not significantly increase the encapsulation of SN-38 within the cores of the resulting SN-38-PNPs. However, it is important to note that even low levels of SN-38 loading in block copolymer PNPs have shown promising in vitro and in vivo anticancer activity in other studies [7][8][9][10]12. Our finding that increasing the MCL content does not significantly increase SN-38 encapsulation is consistent with our earlier finding that increasing the MCL content also did not increase the encapsulation of PAX in the same series of copolymers.19 Mean EE and DL values for SN-38 encapsulation in SN-38-PNPs prepared from the three copolymers are reported inTable…”

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confidence: 99%

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Microfluidic encapsulation of SN-38 in block copolymer nanoparticles: effect of hydrophobic block composition on loading and release properties

et al. 2019

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A gas–liquid microfluidic reactor was used to prepare polymer nanoparticles (PNPs) containing the drug 7-ethyl-10-hydroxy camptothecin (SN-38) from a series of poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) (P(MCL-co-CL)-b-PEO) amphiphilic block copolymers with variable MCL content in the hydrophobic block. All three copolymers formed spheres with ∼20 nm core diameters by TEM, although some rigid rod-like aggregates were also formed by the PMCL-50 and PMCL-75 copolymers. SN-38 encapsulation efficiencies (EE = 2.7%–3.0%) and loading levels (DL = 2.0%–2.9%) were similar for the three copolymers. In vitro release kinetics became significantly slower as the MCL content increased, with release half times increasing monotonically from 3.4 to 6.2 h as the MCL content of the hydrophobic block increased from 50% to 100%. The ability to systematically tune release half times via controlled variation in the hydrophobic block composition, while maintaining constant PNP size and loading levels, represents an intriguing chemical handle for the optimization of SN-38 nanomedicines.

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Efficacy assessment of self-assembled PLGA-PEG-PLGA nanoparticles: Correlation of nano-bio interface interactions, biodistribution, internalization and gene expression studies

Cited by 29 publications

References 50 publications

Preparation of Biodegradable PLGA-Nanoparticles Used for pH-Sensitive Intracellular Delivery of an Anti-inflammatory Bacterial Toxin to Macrophages

Preparation of Biodegradable PLGA-Nanoparticles Used for pH-Sensitive Intracellular Delivery of an Anti-inflammatory Bacterial Toxin to Macrophages

Isolation methods for particle protein corona complexes from protein-rich matrices

Microfluidic encapsulation of SN-38 in block copolymer nanoparticles: effect of hydrophobic block composition on loading and release properties

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