Nanosphere based oral insulin delivery

Carino, Gerardo; Jacob, Jules S.; Mathiowitz, Edith

doi:10.1016/s0168-3659(99)00247-3

Cited by 259 publications

(128 citation statements)

References 14 publications

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“…The direct method began by dissolving NP of known mass into 0.5 ml of 1 M sodium hydroxide and incubating overnight at 37 o C. The solution was then neutralised (1 M HCl), centrifuged for 5 min at 10,000 rpm and the supernatant analysed for total protein content using bicinchoninic acid detection of copper reduction (MicroBCA protein assay kit) (Carino et al, 2000). From this result, the percentage loading (w/w, insulin content per unit mass of dry NP) was determined.…”

Section: Determination Of Insulin Loading and Encapsulation Efficiencymentioning

confidence: 99%

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

Haggag

Abdel-Wahab

Ojo

et al. 2016

International Journal of Pharmaceutics

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A B S T R A C TThe aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (DL-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200-400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3 h to 6 days in type I diabetic mice..

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Section: Determination Of Insulin Loading and Encapsulation Efficiencymentioning

confidence: 99%

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

Haggag

Abdel-Wahab

Ojo

et al. 2016

International Journal of Pharmaceutics

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“…To improve therapeutic efficacy while minimizing side effects, various drug delivery and targeting systems have been investigated such as synthetic polymer-drug conjugates (3), liposomes (4), micelles (5,6), nanogels (7), and micro-or nanosphere (8,9). Nano-sized delivery systems are able to passively accumulate drugs in solid tumors by an enhanced permeation and retention (EPR) effect (10).…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin Loaded pH-sensitive Micelle: Antitumoral Efficacy against Ovarian A2780/DOXR Tumor

Kim¹,

Lee²,

Park³

et al. 2008

Pharm Res

107

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Purpose-To evaluate pH-sensitive mixed micelles for multidrug resistant (MDR) ovarian tumor targeting and optical imaging of solid tumors.Method-Doxorubicin (DOX) encapsulated pH-sensitive mixed micelles composed of poly(Lhistidine) (MW 5K)-b-PEG(MW 2K) and poly(L-lactic acid)(3K)-b-PEG (2K)-folate (PHSM-f) were prepared. Folate receptor-mediated endocytosis, drug uptake, endosomal disruption and cell viability were investigated at the cellular level. For in vivo tumor growth inhibition tests, multidrug resistant ovarian A2780/DOX R xenografted nude mice were used. Optical imaging was performed by using a Cy5.5 fluorescence dye-labeled mixed micelle system. Cy5.5 fluorescence intensity at the tumor site was measured in KB epidermoid xenografted nude mice.Results-In vitro cell viability and drug distribution in the cytoplasm demonstrated the significantly superior efficacy of PHSM-f to free DOX and a control sample of DOX loaded pH-insensitive micelle composed of poly(L-lactic acid)(3K)-b-PEG(2K)/poly(L-lactic acid)(3K)-b-PEG(2K)-folate (80/20 wt/wt%) (PHIM-f). The mechanisms of these results were proved by folate receptor mediated endocytosis of micelle and endosomal disruption function by it. In addition, the optical imaging demonstrated the future application of the diagnositic area. PHSM-f inhibited the growth of multidrug resistant ovarian tumors efficiently in mice, with minimum weight loss.Conclusions-The pH-sensitive mixed micelle system demonstrates effective antitumor efficacy against the multidrug resistant ovarian tumor A2780/DOX R .

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“…The AUC 0-24 is the area under the reduction of blood glucose levels from 0 to 24 h; weight (kg) is the body weight of mice and dose (IU) is the amount of INS administered to the animals (Carino et al, 2000;Pan et al, 2002;Ma et For oral glucose tolerance test, 24 diabetic mice were randomly divided into two groups for 12 mice per group, and then fasted as described above. One group of mice was orally administered with 90 IU/kg of INS plus 100 mg/mouse of surfactin, and another group was orally treated with PB as a placebo control.…”

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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Nanosphere based oral insulin delivery

Cited by 259 publications

References 14 publications

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG

Doxorubicin Loaded pH-sensitive Micelle: Antitumoral Efficacy against Ovarian A2780/DOXR Tumor

A natural lipopeptide of surfactin for oral delivery of insulin

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