Pharmacological effect of orally delivered insulin facilitated by multilayered stable nanoparticles

Woitiski, Camile B.; Neufeld, Ronald J.; Veiga, Francisco; Carvalho, Rui A.; Figueiredo, Isabel V.

doi:10.1016/j.ejps.2010.08.009

Cited by 106 publications

(59 citation statements)

References 47 publications

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“…The solubility was further decreased in our study by the formation of a chitosan-insulin complex with PEG in the precipitation medium. Moreover, by avoiding the use of coprecipitants that have been used by previous investigators, such as tripolyphosphate, 32,33 poly-γ-glutamic acid, 8 and poloxamar, 10 as well as organic solvents, and with minimized use of chitosan (the concentration of which was 1 mg/mL compared with insulin, with a concentration of 10 mg/mL) in the formation of microprecipitates, we were able to improve the loading capacity of insulin in the microparticles to more than 90%. PEG is known to have good biocompatibility and minimal toxicity and is approved by the US Food and Drug Administration for human use.…”

Section: Discussionmentioning

confidence: 99%

“…This is likely because of the poor acid stability of the unencapsulated insulin-chitosan microparticles, leading to uncontrollable burst release and subsequent acute biological responses. Multilayer nanocoatings of chitosan/albumin 10 or Fe 3+ /dextran sulphate 11 have been previously used as the dissolution barrier/sacrificial layer, allowing control over the release kinetics of insulin from microcarriers. However, these coating structures may have poor structural stability at acidic pH conditions as a result of loss of net negative charges in the ionic binding pairs.…”

Section: Discussionmentioning

confidence: 99%

“…2 The main barriers to the intestinal absorption of insulin and a clinically usable oral insulin formulation are the low permeability of proteins across the intestinal wall coupled with high susceptibility to acid denaturation in the stomach and enzymatic degradation throughout the gut. Various strategies for improving gastrointestinal uptake of insulin have been explored, including using carrier systems in which insulin was entrapped in constructs such as nanospheres or nanoparticles, [3][4][5][6][7][8][9] microparticles, 10,11 or liposomes. 12,13 These systems are intended to have the dual role of shielding insulin from the proteolytic/ denaturing processes in the upper gastrointestinal tract and enhancing transmucosal uptake of the hormone from various regions of the small intestine.…”

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confidence: 99%

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Nanolayer encapsulation of insulin- chitosan complexes improves efficiency of oral insulin delivery

Song¹,

Zheng²,

Pickup³

2014

IJN

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Current oral insulin formulations reported in the literature are often associated with an unpredictable burst release of insulin in the intestine, which may increase the risk for problematic hypoglycemia. The aim of the study was to develop a solution based on a nanolayer encapsulation of insulin-chitosan complexes to afford sustained release after oral administration. Chitosan/heparin multilayer coatings were deposited onto insulin-chitosan microparticulate cores in the presence of poly(ethylene) glycol (PEG) in the precipitating and coating solutions. The addition of PEG improved insulin loading and minimized an undesirable loss of the protein resulting from redissolution. Nanolayer encapsulation and the formation of complexes enabled a superior loading capacity of insulin (>90%), as well as enhanced stability and 74% decreased solubility at acid pH in vitro, compared with nonencapsulated insulin. The capsulated insulin administered by oral gavage lowered fasting blood glucose levels by up to 50% in a sustained and dose-dependent manner and reduced postprandial glycemia in streptozotocin-induced diabetic mice without causing hypoglycemia. Nanolayer encapsulation reduced the possibility of rapid and erratic falls of blood glucose levels in animals. This technique represents a promising strategy to promote the intestinal absorption efficiency and release behavior of the hormone, potentially enabling an efficient and safe route for oral insulin delivery of insulin in diabetes management.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Nanolayer encapsulation of insulin- chitosan complexes improves efficiency of oral insulin delivery

Song¹,

Zheng²,

Pickup³

2014

IJN

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“…Solutions of 0.20% calcium chloride, 0.04% chitosan and 0.47% albumin constituted the optimum formulation of nanoparticles for orally-dosed insulin [54]. The relative pharmacological availability and bioavailability were calculated after oral administration of 50 IU/kg of insulin-loaded multilayered nanoparticles to diabetic rats and were found to be 11% and 13%, respectively [55]. Table 4.…”

Section: Natural Polymersmentioning

confidence: 99%

Oral Delivery of Insulin: Novel Approaches

Elsayed¹

2012

Recent Advances in Novel Drug Carrier Systems

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“…Woitiski and colleagues (51) evaluated a multilayered nanoparticle system in which sodium alginate and dextran sulfate were nucleated around calcium, bound to poloxamer 188, stabilized by chitosan, and coated with albumin (51). Human insulin was entrapped in these nanoparticles, which were reported to be spherical, 396 nm in average size but heterogeneous (polydispersity index ϭ 0.6), and negatively charged (-potential ϭ Ϫ38.2 mV).…”

Section: Efficacy Datamentioning

confidence: 99%

A review of the efficacy and safety of nanoparticle-based oral insulin delivery systems

Card

Magnuson

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Card JW, Magnuson BA. A review of the efficacy and safety of nanoparticle-based oral insulin delivery systems. Am J Physiol Gastrointest Liver Physiol 301: G956-G967, 2011. First published September 15, 2011 doi:10.1152/ajpgi.00107.2011.-Nanotechnology is providing new and innovative means to detect, diagnose, and treat disease. In this regard, numerous nanoparticle-based approaches have been taken in an effort to develop an effective oral insulin therapy for the treatment of diabetes. This review summarizes efficacy data from studies that have evaluated oral insulin therapies in experimental models. Also provided here is an overview of the limited safety data that have been reported in these studies. To date, the most promising approaches for nanoparticle-based oral insulin therapy appear to involve the incorporation of insulin into complex multilayered nanoparticles that are mucoadhesive, biodegradable, biocompatible, and acid protected and into nanoparticles that are designed to take advantage of the vitamin B 12 uptake pathway. It is anticipated that the continued investigation and optimization of nanoparticle-based formulations for oral delivery of insulin will lead to a much sought-after noninvasive treatment for diabetes. Such investigations also may provide insight into the use of nanoparticle-based formulations for peptide-and protein-based oral treatment of other diseases and for various foodrelated purposes. nanomaterials; nanotechnology; diabetes DIABETES IS A CHRONIC CONDITION in which the pancreas does not produce enough insulin (Type 1 diabetes) or the body is unable to properly utilize insulin (Type 2 diabetes). It is estimated that the worldwide prevalence of diabetes in adults (20 to 79 yr of age) was 6.6% (285 million people) in 2010 and will increase to 7.8% (438 million people) by the year 2030 (23). Subcutaneous (SC) insulin therapy is a common mode of diabetes treatment but can be burdened by complications (hypoglycemia, edema) and low patient compliance (32). As such, considerable effort has been put forth to develop oral insulin formulations that can provide bioactive insulin in a noninvasive manner that poses minimal patient risk.There are numerous barriers to the oral administration of insulin, including the physical barrier, the enzymatic barrier, and the instability of insulin in the gastrointestinal tract (16, 50). The physical barrier refers to the mucus and viscous fluid (containing mucins, enzymes, electrolytes, and water) that line the epithelium of the small intestine, as well as the physical integrity of the intestinal epithelium attributable to tight junctions between cells. The enzymatic barrier refers to the presence of enzymes in the stomach (pepsin) and duodenum (trypsin, chymotrypsin, and carboxypeptidases) that act to break down proteins and peptides including insulin. The stability of insulin in the gastrointestinal tract is low because of large variations in pH during transit and degradation attributable to enzymatic activity. Combined, these factors contribute to a ...

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Pharmacological effect of orally delivered insulin facilitated by multilayered stable nanoparticles

Cited by 106 publications

References 47 publications

Nanolayer encapsulation of insulin- chitosan complexes improves efficiency of oral insulin delivery

Nanolayer encapsulation of insulin- chitosan complexes improves efficiency of oral insulin delivery

Oral Delivery of Insulin: Novel Approaches

A review of the efficacy and safety of nanoparticle-based oral insulin delivery systems

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