A dual pH/Redox responsive copper-ligand nanoliposome bioactive complex for the treatment of chronic inflammation

Mavuso, Simphiwe; Choonara, Yahya E.; Marimuthu, Thashree; Kumar, Pradeep; Toit, Lisa C. du; Kondiah, Pierre P. D.; Pillay, Viness

doi:10.1016/j.ijpharm.2016.05.069

Cited by 16 publications

(8 citation statements)

References 51 publications

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“…The proposed structures of complex 1 and complex 1a are shown along with the NMR spectra (Figs 3 and 4). The chemical shifts were generally small, implying the minimal delocalisation of spin density from the metal into molecular orbitals of ligands 38 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Characterisation and In Vitro Permeation, Dissolution and Cytotoxic Evaluation of Ruthenium(II)-Liganded Sulpiride and Amino Alcohol

M’bitsi-Ibouily

Marimuthu

Kumar

et al. 2019

Sci Rep

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Sulpiride (SPR) is a selective antagonist of central dopamine receptors but has limited clinical use due to its poor pharmacokinetics. The aim of this study was to investigate how metal ligation to SPR may improve its solubility, intestinal permeability and prolong its half-life. The synthesis and characterisation of ternary metal complexes [Ru(p -cymene)(L)(SPR)]PF6 (L1 = (R)-(+)-2-amino-3-phenyl-1-propanol, L2 = ethanolamine, L3 = (S)-(+)-2-amino-1-propanol, L4 = 3-amino-1-propanol, L5 = (S)-(+)-2-pyrrolidinemethanol) are described in this work. The stability constant of the [Ru(p -cymene)(SPR)] complex was determined using Job’s method. The obtained value revealed higher stability of the metal complex in the physiological pH than in an acidic environment such as the stomach. The ternary metal complexes were characterised by elemental analysis, Fourier transform infrared spectroscopy (FT-IR), 1H and 13C nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), thermal analyses, Ultraviolet-Visible (UV-Vis). Solubility studies showed higher aqueous solubility for complexed SPR than the free drug. Dissolution profiles of SPR from the metal complexes exhibited slower dissolution rate of the drug. Permeation studies through the pig’s intestine revealed enhanced membrane permeation of the complexed drug. In vitro methyl thiazolyl tetrazolium (MTT) assay showed no noticeable toxic effects of the ternary metal complexes on Caco-2 cell line.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Characterisation and In Vitro Permeation, Dissolution and Cytotoxic Evaluation of Ruthenium(II)-Liganded Sulpiride and Amino Alcohol

M’bitsi-Ibouily

Marimuthu

Kumar

et al. 2019

Sci Rep

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“…Mavuso et al . recently described a redox and pH dual‐responsive copper‐ligand nanoliposome bioactive complex for the treatment of chronic inflammation.…”

Section: Methods Of Stimuli‐responsive Drug Deliverymentioning

confidence: 99%

Stimuli‐Responsive Prodrug Chemistries for Drug Delivery

Taresco

Alexander

Singh

et al. 2018

Advanced Therapeutics

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Research into advanced therapeutic materials is of growing importance worldwide, particularly in the disease areas of infection, neurodegeneration, and oncology. Advances have been made in treating these diverse pathologies but there still remain many challenging areas. Amongst the most difficult are those involving highly potent and/or cytotoxic agents which present the inherent problem of adverse off-target effects. Of key importance is to widen the therapeutic window for such agents by reducing access to non-diseased cells and enhancing release at targeted sites. Spatiotemporal controlled release can be achieved by exploiting physical, chemical, or biological stimuli present at the specific diseased area. A crucial strategy involves drug-carrier linkages able to respond to physiological or biochemical stimuli present in the disease region, and there is now significant literature on (polymeric) prodrugs based on the drug + carrier + cleavable linker philosophy, predominantly for cancer applications. The authors therefore focuse this mini-review primarily on single/multistimuli-responsive prodrugs for cancer therapies, covering prominent examples of prodrug chemistries used to endow polymers with controlled and site-specific drug delivery properties. Additionally, the possibilities for exploiting similar approaches to disease-associated stimuli present in bacterial and viral infections, inflammatory and immune diseases, and in degenerative disorders are emphasized.

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“…A major significant difference only occurred at a concentration of 1000 g/mL of the polymer conjugate (63.85% of native polymers conjugate treatment when compared to the control). Thus, this formulation has potential for use in the delivery of cancer therapeutics without toxicity concern since percentage cell viability of 80% or above shows good cytocompatibility of tested formulations [44,45].…”

Section: Confirmation Of Cytocompatibility and Antiangiogenicmentioning

confidence: 98%

Design and Characterization of Endostatin-Loaded Nanoparticles for In Vitro Antiangiogenesis in Squamous Cell Carcinoma

Adeyemi

Choonara

Kumar

et al. 2017

Journal of Nanomaterials

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The aim of this study is to effectively enhance antitumor activities of endostatin by preparing polymeric nanocarriers. NMR and FT-IR spectra confirmed the successful grafting of the CHT-g-PEI and CHT-g-PEI-PEG-NH 2 conjugates. SEM micrographs confirmed the shape of endostatin-loaded nanoparticles to be spherical while both TEM and zeta size results showed nanoparticle's average size to be 100.6 nm having a positively charged surface with zeta potential of 7.95 mV. The concentrations of CHT and TPP as well as the changing pH conditions account for the increased swelling pattern of endostatin-loaded nanoparticles and influenced endostatin release in vitro. PEI increased the overall amine protonation while PEG aggravated endostatin encapsulation and release. Nanoparticles swell and release endostatin at acidic tumor pH of 6.8 compared to physiological pH of 7.4. The native CHT-g-PEI-PEG-NH 2 conjugate showed high cytocompatibility above 80% cell viability across tested formulations. Endostatin-loaded nanoparticles showed a significant reduction in cell viability across tested formulations, with 5.32% cell death at 125 g/mL and 13.36% at 250 g/mL following 24 hours' incubation period. Interestingly, more than a fourfold (61.68%) increment in cytotoxicity was observed at nanoparticle concentration of 1000 g/mL. It was concluded that CHT-g-PEI-PEG-NH 2 is an effective cargo for endostatin delivery with antiangiogenic effect in squamous cell carcinoma.

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A dual pH/Redox responsive copper-ligand nanoliposome bioactive complex for the treatment of chronic inflammation

Cited by 16 publications

References 51 publications

Synthesis, Characterisation and In Vitro Permeation, Dissolution and Cytotoxic Evaluation of Ruthenium(II)-Liganded Sulpiride and Amino Alcohol

Synthesis, Characterisation and In Vitro Permeation, Dissolution and Cytotoxic Evaluation of Ruthenium(II)-Liganded Sulpiride and Amino Alcohol

Stimuli‐Responsive Prodrug Chemistries for Drug Delivery

Design and Characterization of Endostatin-Loaded Nanoparticles for In Vitro Antiangiogenesis in Squamous Cell Carcinoma

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