Oral insulin-delivery System for Diabetes Mellitus

Kanzarkar, Minakshi; Pathak, Prem Prakash; Vaidya, Mandar; Brumlik, Charles J.; Choudhury, Arnab

doi:10.4155/ppa.14.53

Cited by 18 publications

(13 citation statements)

References 24 publications

(23 reference statements)

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“…(Draheim et al 2015;Kanzarkar et al 2015;Park et al 2015;Tang et al 2008;Weerapol et al 2015). Among these techniques, the adsorption process is the simplest and the most commonly used method of transforming formulations from liquid to solid, performed by simply combining them with solid absorbable carriers in a blender.…”

Section: Introductionmentioning

confidence: 99%

Effects of absorbent materials on a self-emulsifying drug delivery system for a poorly water soluble drug

Park

Choi

Kang

2015

Journal of Pharmaceutical Investigation

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In order to compare the effects of a solid carrier on the formulation of a solid self-microemulsifying drug delivery system (s-SMEDDS), a liquid SMEDDS was prepared with simvastatin. The SMEDDS was optimized using polyoxyl 35 castor oil [Kolliphor Ò EL] as a surfactant (S), diethylene glycol monoethylether [Transcutol Ò P] as a co-surfactant (C), and prophyleneglycol monocaprylate [Capryol 90] as the oil phase (O). The microemulsion area at the surfactant to co-surfactant ratio (1:1) was evaluated, and the SMEDDS at an S and C/O ratio of 7:3 was selected. Four types of adsorbents with high specific areas were used: Aerosil Ò 200, Sylysia Ò 350, Neusilin Ò US2, Neusilin Ò UFL2. SEM, DSC, and PXRD results revealed rough-surfaced particles that represent the amorphous state of s-SMEDDS. The optimized formulation with Neusilin Ò UFL2 markedly improved drug release. The present study concluded that s-SMEDDS was effectively formulated via adsorption with solid carriers.

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Section: Introductionmentioning

confidence: 99%

Effects of absorbent materials on a self-emulsifying drug delivery system for a poorly water soluble drug

Park

Choi

Kang

2015

Journal of Pharmaceutical Investigation

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“…Moreover, surfactin can promote INS to permeate the intestine layer by its ''detergent-like'' action on the cell membrane Deleu et al, 2013). Therefore, the biomolecule of surfactin is different from other peptide permeability enhancers such as zonula occludens toxin receptor agonist, which promotes INS permeability by modulating the tight junctions of the epithelial cell membrane (Kanzarkar et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Compared to other proteins/ peptides, e.g. variant-specific surface protein for resisting acidic pH and proteolytic degradation in the GI tract, or aprotinin, soybean trypsin inhibitor and ovomucoid as protease inhibitors (Kanzarkar et al, 2015), surfactin acts as protease inhibitor with different mechanisms for protecting INS from protease digestion. Surfactin can form co-precipitates with INS to resist pepsin degradation in the stomach, and bind to INS to form heteropolymer for inhibiting trypsin attack in the intestine.…”

Section: Discussionmentioning

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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“…Furthermore, this route has several side effects such as peripheral hyperinsulinemia, hypoglycemia, weight gain, fat deposition, etc. (Lim et al., 2014 ; Kanzarkar et al., 2015 ; Sousa et al., 2015 ). For these reasons, numerous researchers attempted to develop noninvasive routes for delivering INS (Nur & Vasiljevic, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Enteric-coated insulin microparticles delivered by lipopeptides of iturin and surfactin

et al. 2017

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Surfactin, a lipopeptide produced by Bacillus species, has been used for the oral delivery of insulin. In this study, another lipopeptide of iturin was tested for its ability to orally delivery insulin alone or plus surfactin. Iturin could form co-precipitate with insulin at acidic pH values. After treatment by ultrasonification, the structure of coprecipitate was destroyed that led to a significant decrease in hypoglycemic effect after oral administration. Iturin weakly binds to (Kd = 257 μM) and induce insulin structure more compact that is favorable for insulin uptake by the intestine. After being coated with Acryl-Eze by lyophilization, the coprecipitate formed the spherical enteric-coated insulin microparticles delivered by iturin with a relative oral bioavailability of 6.84% in diabetic mice. For further improving oral hypoglycemic effect, surfactin was added to form the spherical enteric-coated insulin microparticles in a formulation containing insulin, Acryl-Eze, iturin and surfactin at a ratio of 1:1:0.5: 0.5 (w/w), with an insulin encapsulation efficiency of 66.22%. The enteric-coated insulin microparticles delivered by iturin plus surfactin showed a classical profile for controlled release in the intestine with a relative bioavailability of 7.67% after oral administration, which could effectively control the postprandial blood glucose at a level about 50% of the initial one just like the subcutaneous injection. Collectively, iturin plus surfactin is more efficient for oral delivering insulin than the sole one, and the resultant enteric-coated insulin microparticles are potential for the development of oral insulin to control postprandial blood glucose in diabetic patients.

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Oral insulin-delivery System for Diabetes Mellitus

Cited by 18 publications

References 24 publications

Effects of absorbent materials on a self-emulsifying drug delivery system for a poorly water soluble drug

Effects of absorbent materials on a self-emulsifying drug delivery system for a poorly water soluble drug

A natural lipopeptide of surfactin for oral delivery of insulin

Enteric-coated insulin microparticles delivered by lipopeptides of iturin and surfactin

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