Biodistribution, pharmacodynamics and pharmacokinetics of insulin analogues in a rat model: Oral delivery using pH-Responsive nanoparticles vs. subcutaneous injection

Sonaje, Kiran; Lin, Kun‐Ju; Wey, Shiaw-Pyng; Lin, Che-Kuan; Yeh, Tzyy-Harn; Nguyen, Ho-Ngoc; Hsu, Chia‐Wei; Yen, Tzu‐Chen; Juang, Jyuhn‐Huarng; Sung, Hsing‐Wen

doi:10.1016/j.biomaterials.2010.05.042

Cited by 175 publications

(108 citation statements)

References 37 publications

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“…26 The Fmoc-protected CPP sequence was covalently conjugated to the surface amine groups of the preformed NP using carbodiimide chemistry. 27 Briefly, Fmoc-CPP sequence was solubilized in distilled water (20 mg/mL) and completely mixed with NHS (40% w/w) and ethylenediaminetetraacetic acid (EDTA) (60% w/w) and stirred for 2 h at RT. Aqueous dispersion of preformed CS NPs (200 mg/mL) was added to the reaction mixture and stirred at RT for 20 h. The CPP-NP conjugates were dialyzed extensively against distilled water for 2 days in dialysis bags with Mw cutoff point of 12,000 Da and lyophilized.…”

Section: Optimization With Doementioning

confidence: 99%

A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

Barbari¹,

Dorkoosh²,

Amini³

et al. 2017

IJN

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A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O nanoemulsion serve as “nano-containers and nano-reactors”. The entrapped polymer chains of CS inside these “nano-reactors” are covalently cross-linked with the chains of polyethylene glycol (PEG), leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG. A potent and newly developed cell-penetrating peptide (CPP) is further chemically conjugated to the surface of the NPs, leading to development of a novel peptide-conjugated derivative of CS with profound tight-junction opening properties. The CPP-conjugated NPs can easily be loaded with almost all kinds of proteins, peptides and nucleotides for oral delivery applications. Feasibility of this nanoparticulate system for oral delivery of a model peptide (insulin) is investigated in Caco-2 cell line. The cell culture results for translocation of insulin across the cell monolayer are very promising (15%–19% increase), and animal studies are actively under progress and will be published separately.

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Section: Optimization With Doementioning

confidence: 99%

A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

Barbari¹,

Dorkoosh²,

Amini³

et al. 2017

IJN

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show abstract

“…Upon intestinal absorption, nutritional compounds are transported directly to the liver via the hepatic portal vein 33. The mammalian liver contains many resident macrophages (Kupffer cells), which are efficient in the uptake and retention of foreign particles that circulate in the bloodstream (Figure 5B) 34.…”

Section: Discussionmentioning

confidence: 99%

Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy

et al. 2018

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Efficient nonviral oral gene delivery offers an attractive modality for chronic protein replacement therapy. Herein, the oral delivery of insulin gene is reported by a nonviral vector comprising a copolymer with a high degree of substitution of branched polyethylenimine on chitosan (CS‐g‐bPEI). Protecting the plasmid from gastric acidic degradation and facilitating transport across the gut epithelium, the CS‐g‐bPEI/insulin plasmid DNA nanoparticles (NPs) can achieve systemic transgene expression for days. A single dose of orally administered NPs (600 µg plasmid insulin (pINS)) to diabetic mice can protect the animals from hyperglycemia for more than 10 d. Three repeated administrations spaced over a 10 d interval produce similar glucose‐lowering results with no hepatotoxicity detected. Positron‐emission‐tomography and computed‐tomography images also confirm the glucose utilization by muscle cells. While this work suggests the feasibility of basal therapy for diabetes mellitus, its significance lies in the demonstration of a nonviral oral gene delivery system that can impact chronic protein replacement therapy and DNA vaccination.

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“…3,4 Orally delivered insulin undergoes a hepatic bypass before entering the circulation, so it has the potential to mimic the effects of pancreas-secreted insulin in terms of inhibiting hepatic gluconeogenesis and hepatic glucose output. [5][6][7][8] Many different strategies have been attempted to develop a biologically active oral insulin formulation. It is generally acknowledged that degradation of protein drug by the harsh conditions of the gastrointestinal (GI) tract, including gastric medium and digestive enzymes, is a major obstacle.…”

Section: Introductionmentioning

confidence: 99%

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

Sun¹,

Liang²,

Yamamoto³

et al. 2015

IJN

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This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin–sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit ® FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery.

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Biodistribution, pharmacodynamics and pharmacokinetics of insulin analogues in a rat model: Oral delivery using pH-Responsive nanoparticles vs. subcutaneous injection

Cited by 175 publications

References 37 publications

A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

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