Opsonized erythrocyte ghosts for liver-targeted delivery of antisense oligodeoxynucleotides

Kim, Sanghee; Kim, Eunjoong; Hou, Joon-Hyuk; Kim, Jung Mogg; Choi, Hyun Seok; Shim, Chang‐Koo; Oh, Yu‐Kyoung

doi:10.1016/j.biomaterials.2008.10.031

Cited by 30 publications

(19 citation statements)

References 23 publications

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“…ODN concentrations in cell lysate were determined spectrofluorimetrically as reported earlier [105–107]. After incubation period, transfection medium was removed and cells were washed three times with ice cold PBS (8 g/L NaCl, 0.2 g/L KCl, 1.56 g/L Na 2 HPO 4, and 0.2 g/L KH 2 PO 4 in water at pH 7.2).…”

Section: Characterization Of Mchodn Nanoparticlesmentioning

confidence: 99%

Mannosylated Chitosan Nanoparticles for Delivery of Antisense Oligonucleotides for Macrophage Targeting

Asthana

Kohli

et al. 2014

BioMed Research International

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The therapeutic potential of antisense oligonucleotides (ASODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study focuses on designing mannosylated low molecular weight (LMW) chitosan nanoconstructs for safe ODNs delivery by macrophage targeting. Mannose groups were coupled with LMW chitosan and characterized spectroscopically. Mannosylated chitosan ODN nanoparticles (MCHODN NPs) were formulated by self-assembled method using various N/P ratio (moles of amine groups of MCH to phosphate moieties of ODNs) and characterized for gel retardation assay, physicochemical characteristics, cytotoxicity and transfection efficiency, and antisense assay. Complete complexation of MCH/ODN was achieved at charge ratio of 1:1 and above. On increasing the N/P ratio of MCH/ODN, particle size of the NPs decreased whereas zeta potential (ZV) increased. MCHODN NPs displayed much higher transfection efficiency into Raw 264.7 cells (bears mannose receptors) than Hela cells and no significant toxicity was observed at all MCH concentrations. Antisense assay revealed that reduction in lipopolysaccharide (LPS) induced serum TNF-α is due to antisense activity of TJU-2755 ODN (sequence complementary to 3′-UTR of TNF-α). These results suggest that MCHODN NPs are acceptable choice to improve transfection efficiency in vitro and in vivo.

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Section: Characterization Of Mchodn Nanoparticlesmentioning

confidence: 99%

Mannosylated Chitosan Nanoparticles for Delivery of Antisense Oligonucleotides for Macrophage Targeting

Asthana

Kohli

et al. 2014

BioMed Research International

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“…Examples of pharmacological and imaging agents encapsulated into carrier RBC include diverse enzymes29,30, fluorescent labels30, erythropoietin for sustained stimulation of hemopoietic potential31, hemoglobin cofactor inositol hexaphosphate for enhancing RBC oxygen carrying capacity32,33, anti-thrombotic drugs heparin34 and thrombolytics35, amikacin for anti-parasitic therapy36,37, insulin38, fluoro-AMP25 and methotrexate for cancer chemotherapy35, isotopes for imaging of blood pool using gamma-scintigraphy and MRI39–42, antisense oligonucleotides for gene knock-outs43 and anti-viral interventions44, plasmid DNA for gene therapy45, and, more recently, magnetic nanoparticles46.…”

Section: Vascular Delivery Of Drugs Encapsulated Into Carrier Rbcmentioning

confidence: 99%

“…Organ distribution, pharmacokinetics and effects of some of these drug delivery systems have been tested in studies in lab animal species32,43 and, in a more fragmentary fashion, in human patients42,47–49. Some of these studies provided rather mixed results, perhaps, due to unintended damage inflicted to carrier RBC during drug loading that compromised its biocompatibility, or variability and heterogeneity of RBC loading (noted even within the same batch in the early studies)29,30.…”

Section: Vascular Delivery Of Drugs Encapsulated Into Carrier Rbcmentioning

confidence: 99%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

340

294

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Importance of the field-Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBCencapsulated drugs are been currently explored in patients illustrates a high biomedical importance for the field.Areas covered by this review-Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators is d escribed. Also described is a novel, translation-prone approach for RBC drug delivery by injecting of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC.What the reader will gain-The readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery.Take home message-RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. Novel approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system.

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“…Besides that, it also has the remarkable long life span of about 3 months in the body [5]. Therefore, small-molecule drugs (doxorubicin [6], dexamethasone sodium phosphate [7]), enzyme (pegademase, adenosine deaminase [8], L-Asprraginase [9]), nucleoside (FdUMP [10], antisense oligodeoxynucleotides [11]), and nanoparticles [12] have been encapsulated in erythrocyte. In recent years, nanoparticles derived from erythrocyte (Nano-RBCs), have strongly attracted the attention of investigators due to the virtue inherited from their parent cells.…”

Section: Introductionmentioning

confidence: 99%

Formulation and Drug Loading Features of Nano-Erythrocytes

et al. 2017

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Nano erythrocyte ghosts have recently been used as drug carriers of water-soluble APIs due to inherit biological characteristics of good compatibility, low toxicity, and small side-effect. In this study, we developed a novel drug delivery system based on nano erythrocyte ghosts (STS-Nano-RBCs) to transport Sodium Tanshinone IIA sulfonate (STS) for intravenous use in rat. STS-Nano-RBCs were prepared by hypotonic lysis and by extrusion methods, and its biological properties were investigated compared with STS injection. The results revealed that STS-Nano-RBCs have narrow particle size distribution, good drug loading efficiency, and good stability within 21 days. Compared with STS injection, STS-Nano-RBCs extended the drug release time in vitro and in vivo with better repairing effect on oxidative stress-impaired endothelial cells. These results suggest that the nano erythrocyte ghosts system could be used to deliver STS.

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Opsonized erythrocyte ghosts for liver-targeted delivery of antisense oligodeoxynucleotides

Cited by 30 publications

References 23 publications

Mannosylated Chitosan Nanoparticles for Delivery of Antisense Oligonucleotides for Macrophage Targeting

Mannosylated Chitosan Nanoparticles for Delivery of Antisense Oligonucleotides for Macrophage Targeting

Drug delivery by red blood cells: vascular carriers designed by mother nature

Formulation and Drug Loading Features of Nano-Erythrocytes

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