Polymethyacrylate based microparticulates of insulin for oral delivery: Preparation and in vitro dissolution stability in the presence of enzyme inhibitors

Agarwal, Vikas; Reddy, Indra K.; Khan, Mansoor A.

doi:10.1016/s0378-5173(01)00740-2

Cited by 46 publications

(22 citation statements)

References 19 publications

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“…The spontaneously precipitating complexes were separated from aqueous phase by centrifugation at 6000g for 20 min at 4°C. The precipitated complexes were washed two times with Tris buffer and dried under vacuum for 24 h. The supernatant containing non-associated insulin was collected and the amount of free insulin was measured by reversed phase high performance liquid chromatography (HPLC) [41]. A Dionex HPLC system consisting of a helium out-gasser, a gradient pump GP 50, a LC30 oven equipped with auto injection port, 25 lL loop, a 218MR54 column (4.6 Â 250 mm, 5 lm particle size, C18, Vydac, USA) and a PDA 100 photodiode array UV detector set at 218 nm was employed.…”

Section: Synthesis Of Guanidinylated Poly(l-lysine) Dendrigraftsmentioning

confidence: 99%

Arginine end-functionalized poly(l-lysine) dendrigrafts for the stabilization and controlled release of insulin

Sideratou

Sterioti

Tsiourvas

et al. 2010

Journal of Colloid and Interface Science

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Section: Synthesis Of Guanidinylated Poly(l-lysine) Dendrigraftsmentioning

confidence: 99%

Arginine end-functionalized poly(l-lysine) dendrigrafts for the stabilization and controlled release of insulin

Sideratou

Sterioti

Tsiourvas

et al. 2010

Journal of Colloid and Interface Science

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“…Low membrane permeability and inadequate stability restricts the potential use of insulin across the transmucosal routes. Protease inhibitors, permeation enhancers, enteric coatings and polymeric microsphere formulations have all been employed towards the development of transmucosal insulin formulations with varying degrees of success (22)(23)(24)(25). One possibility to improve the gastrointestinal uptake of perorally poorly absorbed drugs like insulin is their binding to colloidal particles can protect labile molecules from degradation in the gastrointestinal tract and promote the transport of poor-absorbable molecules into systemic circulation.…”

Section: Introductionmentioning

confidence: 99%

Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin

et al. 2007

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Purpose. Colloidal metallic systems have been recently investigated in the area of nanomedicine. Gold nanoparticles have found themselves useful for diagnostic and drug delivery applications. Herein we have reported a novel method for synthesis of gold nanoparticles using a natural, biocompatible and biodegradable polymer; chitosan. Use of chitosan serves dual purpose by acting as a reducing agent in the synthesis of gold nanoparticles and also promotes the penetration and uptake of peptide hormone insulin across the mucosa. To demonstrate the use of chitosan reduced gold nanoparticles as carriers for drug delivery, we report herein the transmucosal delivery of insulin loaded gold nanoparticles. Materials and Methods. Gold nanoparticles were prepared using different concentrations of chitosan (from 0.01% w/v up to 1% w/v). The gold nanoparticles were characterized for surface plasmon band, zeta potential, surface morphology, in vitro diffusion studies and fluorescence spectroscopy. The in vivo studies in diabetic male Wistar rats were carried out using insulin loaded chitosan reduced gold nanoparticles.Results. Varying concentrations of chitosan used for the synthesis of gold nanoparticles demonstrated that the nanoparticles obtained at higher chitosan concentrations (>0.1% w/v) were stable showing no signs of aggregation. The nanoparticles also showed long term stability in terms of aggregation for about 6 months. Insulin loading of 53% was obtained and found to be stable after loading. Blood glucose lowering at the end of 2 h following administration of insulin loaded gold nanoparticles to diabetic rats was found to be 30.41 and 20.27% for oral (50 IU/kg) and nasal (10 IU/kg), respectively. Serum gold level studies have demonstrated significant improvement in the uptake of chitosan reduced gold nanoparticles. Conclusions. The synthesis of gold nanoparticles using a biocompatible polymer, chitosan would improve its surface properties for binding of biomolecules. Our studies indicate that oral and nasal administration of insulin loaded chitosan reduced gold nanoparticles has led to improved pharmacodynamic activity. Thus, chitosan reduced gold nanoparticles loaded with insulin prove to be promising in controlling the postprandial hyperglycemia.

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“…Although oral administration of insulin is of greatest interest, its low bioavailability has not permitted to achieve an efficient formulation. The entrapment within microparticulate drug delivery systems, using various kinds of polymers and techniques has been extensively investigated (Damge et al, 1988;Morishita et al, 1992;Mathiowitz et al, 1997;Lowman et al, 1999;Agarwal et al, 2001) to increase the poor permeability across intestinal epithelia and avoid destruction by proteolytic intestinal enzymes. However, in the development of new protein delivery methods, there are several key points that have to be considered, namely, the impact of manufacturing on the integrity of the protein (Cleland et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Alginate microspheres prepared by internal gelation: Development and effect on insulin stability

Silva

Ribeiro

Figueiredo

et al. 2006

International Journal of Pharmaceutics

177

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Recombinant human insulin was encapsulated within alginate microspheres by the emulsification/internal gelation technique with the objective of preserving protein stability during encapsulation procedure. The influence of process and formulation parameters was evaluated on the morphology and encapsulation efficiency of insulin. The in vitro release of insulin from microspheres was studied under simulated gastrointestinal conditions and the in vivo activity of protein after processing was assessed by subcutaneous administration of extracted insulin from microspheres to streptozotocin-induced diabetic rats. Microspheres mean diameter, ranging from 21 to 287 m, decreased with the internal phase ratio, emulsifier concentration, mixer rotational speed and increased with alginate concentration. Insulin encapsulation efficiency, near 75%, was not affected by emulsifier concentration, mixer rotational speed and zinc/insulin hexamer molar ratio but decreased either by increasing internal phase ratio and calcium/alginate mass ratio or by decreasing acid/calcium molar ratio and alginate concentration. A high insulin release, above 75%, was obtained at pH 1.2 and under simulated intestinal pH a complete dissolution of microspheres occurred. Extracted insulin from microspheres decreased hyperglycemia of diabetic rats proving to be bioactive and showing that encapsulation in alginate microspheres using the emulsification/internal gelation is an appropriate method for protein encapsulation.

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Polymethyacrylate based microparticulates of insulin for oral delivery: Preparation and in vitro dissolution stability in the presence of enzyme inhibitors

Cited by 46 publications

References 19 publications

Arginine end-functionalized poly(l-lysine) dendrigrafts for the stabilization and controlled release of insulin

Arginine end-functionalized poly(l-lysine) dendrigrafts for the stabilization and controlled release of insulin

Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin

Alginate microspheres prepared by internal gelation: Development and effect on insulin stability

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