In vivo evaluation of safety and efficacy of self-assembled nanoparticles for oral insulin delivery

Sonaje, Kiran; Lin, Yu Hsin; Juang, Jyuhn Huarng; Wey, Shiaw-Pyng; Chen, Chiung Tong; Sung, Hsing‐Wen

doi:10.1016/j.biomaterials.2008.12.066

Cited by 263 publications

(182 citation statements)

References 35 publications

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“…The negative charge demonstrates that AG has formed complex with CH and helped in concealing CH from degradation in the gastric environment. Ex vivo permeation studies indicated that the enhanced transport of PEC nanoparticles was ascribed to the mucoadhesive property of CH and the size of nanoparticles [28].…”

Section: Discussionmentioning

confidence: 99%

Novel Nanoparticles for the Oral Delivery of Low Molecular Weight Heparin: In Vitro and in Vivo Assessment

Nallaguntla

Muzib

Aukunuru³

et al. 2017

Asian J Pharm Clin Res

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Objective: The objective of the present study was to prepare and evaluate a novel oral formulation of nanoparticles for the systemic delivery of lowmolecular-weight heparin (LMWH).Methods: Nanoparticles were prepared by polyelectrolyte complexation method using polymers, i.e., sodium alginate and chitosan (CH). Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency, In vitro release and scanning electron microscopic studies were carried out for nanoparticles. Ex vivo permeation studies were performed with optimized formulation using small intestine of rat and in vivo studies were conducted on rat model. Results:Entrapment efficiency of LMWH in nanoparticles was found to be 88%. In vitro release studies demonstrated that the release of LMWH was negligible in the stomach and high in the small intestine. FTIR has indicated that there is no interaction between the ingredients in nanoparticle. DSC and XRD studies confirmed that the amino groups of CH interacted with the carboxylic groups of alginate. In vitro % drug release of 95% was shown by formulation AC5. Ex vivo permeation studies have elucidated that ~73% of LMWH was transported across the epithelium. Nanoparticles have shown enhanced oral bioavailability of LMWH as revealed by 4.5-fold increase in area under the curve of plasma drug concentration-time curve. Conclusion:The results suggest that the nanoparticles prepared can result in targeted delivery of LMWH into systemic circulation through intestinal and colon routes. Novel nanoparticles thus prepared in this study can be considered as a promising delivery system.

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Section: Discussionmentioning

confidence: 99%

Novel Nanoparticles for the Oral Delivery of Low Molecular Weight Heparin: In Vitro and in Vivo Assessment

Nallaguntla

Muzib

Aukunuru³

et al. 2017

Asian J Pharm Clin Res

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“…where F is the fasting blood glucose level, Pt is the blood glucose level at time (t) post-administration (Rekha & Sharma, 2009;Sonaje et al, 2009;Sajeesh et al, 2010;Makhlof et al, 2011). For determination of oral BA of INS plus surfactin, 24 diabetic mice were randomly divided into two groups for 12 mice per group and fasted as described above.…”

Section: Determination Of Hypoglycemic Effects Of Oral Ins Plus Surfamentioning

confidence: 99%

A natural lipopeptide of surfactin for oral delivery of insulin

et al. 2016

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Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid a-helix and b-turn, but with increased flexible b-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.

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“…The toxicity test of CHSPNs was carried out in vivo to clarify its applicability in a biosystem according to the previous reported methods (Yoksan & Chirachanchai, 2008;Sonaje et al, 2009). Adult male (22-24 g) and female ICR mice (18-22 g) were randomly divided into two groups with each of 10 mice.…”

Section: In Vivo Toxicitymentioning

confidence: 99%

The preliminary evaluation on cholesterol-modified pullulan as a drug nanocarrier

Shen

Yang

2014

Drug Delivery

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To further develop cholesterol-modified pullulan self-aggregated nanoparticles (CHSPNs) as a drug nanocarrier, CHSP was synthesized and characterized. Its cholesterol degree determined by 1 H NMR was 5.2 cholesterol groups per hundred glucose units. CHSPNs were prepared in aqueous media and characterized by dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM). These nanoparticles were almost spherical in shape, and the zeta potentials of CHSPNs were near zero in aqueous media. CHSPNs can be stable at least 2 months with no significant size and zeta potential changes. Single dose toxicity test in mice was investigated for the safety evaluation of CHSPNs as a drug nanocarrier, and the result showed CHSPNs were well tolerated at the dose of 200 mg/kg in mice. Epirubicin (EPI)-loaded CHSPNs (EPI-CHSPNs) were prepared and the in vivo pharmacokinetics and biodistribution were studied. Compared with the EPI solution, EPI-CHSPNs have exhibited higher plasma drug concentration, longer half-life time (t 1/2 ) and the larger area under-the-curve (AUC). Moreover, the drug level of EPI-CHSPNs increased in liver and decreased in heart. The results indicated that CHSPNs were stable, safe and may be a promising drug delivery carrier.

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In vivo evaluation of safety and efficacy of self-assembled nanoparticles for oral insulin delivery

Cited by 263 publications

References 35 publications

Novel Nanoparticles for the Oral Delivery of Low Molecular Weight Heparin: In Vitro and in Vivo Assessment

Novel Nanoparticles for the Oral Delivery of Low Molecular Weight Heparin: In Vitro and in Vivo Assessment

A natural lipopeptide of surfactin for oral delivery of insulin

The preliminary evaluation on cholesterol-modified pullulan as a drug nanocarrier

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