Stabilization of Insulin by Adsorption on a Hydrophobic Silane Self-Assembled Monolayer

Mauri, Sergio; Völk, Martin; Byard, Stephen J.; Berchtold, Harald; Arnolds, Heike

doi:10.1021/acs.langmuir.5b01477

Cited by 18 publications

(18 citation statements)

References 55 publications

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“…Extensive research has been conducted on the surface adsorption of human insulin [171,[173][174][175][176][177]. It is well known that insulin aggregates to form fibres in the presence of hydrophobic surfaces [170,171,175,176] and especially in a peristaltic pump system [177].…”

Section: Surfaces and Interfacesmentioning

confidence: 99%

Factors affecting the physical stability (aggregation) of peptide therapeutics

Zapadka

Becher

Santos³

et al. 2017

Interface Focus.

265

207

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The number of biological therapeutic agents in the clinic and development pipeline has increased dramatically over the last decade and the number will undoubtedly continue to increase in the coming years. Despite this fact, there are considerable challenges in the development, production and formulation of such biologics particularly with respect to their physical stabilities. There are many cases where self-association to form either amorphous aggregates or highly structured fibrillar species limits their use. Here, we review the numerous factors that influence the physical stability of peptides including both intrinsic and external factors, wherever possible illustrating these with examples that are of therapeutic interest. The effects of sequence, concentration, pH, net charge, excipients, chemical degradation and modification, surfaces and interfaces, and impurities are all discussed. In addition, the effects of physical parameters such as pressure, temperature, agitation and lyophilization are described. We provide an overview of the structures of aggregates formed, as well as our current knowledge of the mechanisms for their formation.

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Section: Surfaces and Interfacesmentioning

confidence: 99%

Factors affecting the physical stability (aggregation) of peptide therapeutics

Zapadka

Becher

Santos³

et al. 2017

Interface Focus.

265

207

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“…The FTIR spectra of A) insulin, B) nanogels, C) trehalose, D) lyophilized blank formulation containing trehalose, and E) InF12-Tre2 formulation is presented in Figure 3. The insulin shows a characteristic broad peak at 1649 cm–1 23. The FTIR spectra of nanogels shows increased peak intensity of the C=O group at 1731.49 cm –1 which was associated with the presence of the additional C=O groups from itaconic acid.…”

Section: Resultsmentioning

confidence: 98%

<p>Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation</p>

Mudassir

Darwis

Muhamad

et al. 2019

IJN

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Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, −16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, −16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.

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“…Histological evaluation of tissue samples from rabbits in the experimental oral microparticles. a Intestinal mucosal crypts confirm normal intestinal mucosa (×10 magnification), b intestinal mucosa which shows normal epithelium (×10 magnification), c fundic portion of the stomach which shows normal fundic glands (×10 magnification), d severe loss of cellularity and necrosis of the islet cells in the islet of Langerhans of rabbits induced with diabetes in the insulin study (×20 magnification) after particle entrapment; however, a significant change was observed in the denatured protein samples (23,31). All proteins obtained significant in vivo responses, as discussed extensively in the following section.…”

Section: Particle Size Distribution Protein-loading Efficiency and In Vitro Evaluation Of The Copolymeric Microparticlesmentioning

confidence: 99%

Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System

et al. 2017

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A multifunctional platform to deliver three diverse proteins of insulin, interferon beta (INF-β) and erythropoietin (EPO), using a novel copolymeric microparticulate system of TMC-PEGDMA-MAA, was synthesised as an intelligent pH-responsive 2-fold gastric and intestinal absorptive system. Physiochemical and physicomechanical studies proved the degree of crystallinity that supported the controlled protein delivery of the microparticulate system. The copolymer was tableted before undertaking in vitro and in vivo analysis. After 2.5 h in simulated gastric fluid (SGF), insulin showed a fractional release of 3.2% in comparison to simulated intestinal fluid (SIF), in which a maximum of 83% of insulin was released. Similarly, INF-β and EPO released 3 and 9.7% in SGF and a maximum of 74 and 81.3% in SIF, respectively. In vivo studies demonstrated a significant decrease in blood glucose by 54.19% within 4 h post-dosing, and the comparator formulation provided 74.6% decrease in blood glucose within the same time period. INF-β peak bioavailable dose in serum was calculated to be 1.3% in comparison to an SC formulation having a peak concentration of 0.9%, demonstrating steady-state release for 24 h. EPO-loaded copolymeric microparticles had a 1.6% peak bioavailable concentration, in comparison to the 6.34% peak concentration after 8 h from the SC comparator formulation.

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Stabilization of Insulin by Adsorption on a Hydrophobic Silane Self-Assembled Monolayer

Cited by 18 publications

References 55 publications

Factors affecting the physical stability (aggregation) of peptide therapeutics

Factors affecting the physical stability (aggregation) of peptide therapeutics

<p>Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation</p>

Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System

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