Search

Subcutaneous insulin injection is mainly used to treat diabetes, but it has limitations, such as hyperinsulinemia, adipose tissue atrophy and hypoglycemia. As a simple way of administration, oral insulin can reduce side effects and improve patients ’ compliance. However, protein drugs can be inactivated by gastrointestinal enzymes after oral administration. In recent years, with the rapid development of nanotechnology, targeted nano-delivery systems have been widely used in the study of oral insulin. Compared with unmodified nanocarriers, targeted nano delivery system has obvious advantages. Insulin can not only be loaded by it, but also smoothly pass through the gastrointestinal barrier and be successfully transported to the site of action. At the same time, the structural stability of insulin can also be protected, so as to maintain its biological activity and finally achieve mild hypoglycemic effect. Therefore, targeted oral delivery of insulin is promising to replace the common subcutaneous injection of insulin and provide painless treatment for diabetic patients. The ligand-modified targeting nanocarriers enhance the intestinal absorption and transport of insulin by specifically binding to receptors on the surface of intestinal cells and play a mild hypoglycemic effect. The main characteristics, targeting mechanism and main factors affecting the targeting effect of targeting nanocarriers are discussed. The main factors include the size, shape and ligand density of nanoparticles. The design ideas, research methods and oral bioavailability of nano-carriers modified with different surface ligands are reviewed in detail. These targeting ligands are folic acid (FA), fragment crystallizable (Fc), biotin, polypeptide, transferrin and VB12. The existing problems and future development directions of targeting nanocarriers for oral insulin are also put forward. [ABSTRACT FROM AUTHOR]

A large number of people are suffering with one or the other type of diabetes around the globe. Insulin has proven to be beneficial for the treatment of both types of diabetes. Due to the drawbacks (injection pain, needle phobia, lipodystrophy, noncompliance peripheral hyperinsulinemia, failure to deliver physiological pattern of insulin, and daily metabolic variability in glycemic control) associated with a conventional delivery system that is, the subcutaneous injection, a need to develop new insulin delivery system was felt strongly. A few noninvasive methods which are under process to deliver insulin include per-oral (enteric gastrointestinal route), intrapulmonary, buccal, intranasal, oropharyngeal, rectal, intrauterine, ocular, transdermal, oral, and vaginal. Intranasal insulin is fetching tons of importance as it provides multiple reasons to choose this method of delivery over other delivery systems. Certain factors are responsible for limiting the use of intranasal insulin for which various methods have been studied to overcome it. Many clinical trials are going on for launching intranasal insulin into the market.

Copyright of Revista de la ALAD is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A large number of people are suffering with one or the other type of diabetes around the globe. Insulin has proven to be beneficial for the treatment of both types of diabetes. Due to the drawbacks (injection pain, needle phobia, lipodystrophy, noncompliance peripheral hyperinsulinemia, failure to deliver physiological pattern of insulin, and daily metabolic variability in glycemic control) associated with a conventional delivery system that is, the subcutaneous injection, a need to develop new insulin delivery system was felt strongly. A few noninvasive methods which are under process to deliver insulin include per-oral (enteric gastrointestinal route), intrapulmonary, buccal, intranasal, oropharyngeal, rectal, intrauterine, ocular, transdermal, oral, and vaginal. Intranasal insulin is fetching tons of importance as it provides multiple reasons to choose this method of delivery over other delivery systems. Certain factors are responsible for limiting the use of intranasal insulin for which various methods have been studied to overcome it. Many clinical trials are going on for launching intranasal insulin into the market. [ABSTRACT FROM AUTHOR]

Regardless of age, diabetes is one of the most prevalent diseases that people deal with. There are several various types of diabetes medications available, but metformin is the most popular. This primary purpose of this article is to provide a comparison of various dosage forms used for treatment of diabetes. However, oral insulin therapy has a number of potential advantages and would be practical for patients. The study and development of oral insulin is a fascinating subject in the study of diabetes. We are making progress toward creating an insulin formulation that won't require injections before to meals, which will enhance the quality of life and mental health of more than nine million type 1 diabetics worldwide. Despite the fact that it is only currently available in injectable form, insulin is nevertheless crucial for the management of diabetes. The ultimate goal for improving simplicity of use and providing therapeutic benefits stemming from its direct distribution to the portal vein and liver is the development of an oral insulin. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Compliance to insulin injections is poor due to difficulty in subcutaneous administration. Hence, there is a need of an oral formulation of insulin. Oral insulin is currently under investigation. The present analysis aimed to evaluate oral insulin versus placebo for patients with diabetes mellitus (type-1 and type-2). MATERIALS AND METHODS: Results from PUBMED and MEDLINE were searched and compiled from January 1, 2000 to January 9, 2020. Postprandial blood glucose excursions (2PPG), glycated hemoglobin (HbA1c), C-peptide levels, and immune antibody (IAA) levels were compared between the arms. In addition, time to diabetes and safety of oral insulin were discussed. RESULTS: Thirteen out of 1778 trials were included to the analysis. Oral insulin was found to induce significant reduction in mean 2PPG excursion (standardized mean difference [SMD]: −1.94, 95% CI: −3.20 to −0.68, I2 = 91.81, P < 0.005) and mean IAA levels (SMD:-0.49, 95% CI: −0.82 to -0.16, I2 = 27.12, P < 0.005) compared with placebo. Mean C-peptide levels were notably lower in the oral insulin arm. However, the difference was not statistically significant. No significant difference was observed in mean HbA1c levels. The rate of development of type-1 diabetes was not significantly influenced by oral insulin. No deaths or treatment-related serious adverse events were reported. CONCLUSION: Oral insulin provided significant benefits for acute maintenance of diabetes mellitus. It elicited lower immune response and was well tolerated. This new formulation has potential to augment the management of diabetes mellitus. More studies are required to assess its long-term effects. [ABSTRACT FROM AUTHOR]

Oral delivery is an ideal method of insulin administration and is currently a promising research field. Here, we evaluated the safety, pharmacokinetic, and pharmacodynamic characteristics of oral administration of an insulin capsule (ORMD‐0801) with 2 different sources of recombinant human insulin. This was a single‐center, randomized, double‐blind, placebo‐controlled, dose‐escalating phase 1 trial. Single dosing of the oral insulin capsule was administered in 70 healthy Chinese subjects. In stage 1, four dose groups (8, 16, 32, and 48 mg) for capsules containing Sanofi insulin and in stage 2, three dose groups (8, 32, and 48 mg) containing Hefei Tianmai insulin were evaluated consequently. The results showed that the oral insulin formulations with either source in the dose range 8 to 48 mg were safe, and no serious adverse events were observed. After a standard breakfast 45 minutes after dosing, the area under the concentration‐time curve (AUC) from time 0 to time t and AUC from time 0 to infinity for insulin in the 8‐mg and 48‐mg dose groups in stage 1 and for 8‐ to 48‐mg groups in stage 2 were slightly increased compared with placebo, but no significant dose‐related changes in the pharmacokinetic parameters were observed for either stage. The peak‐valley difference and the change in value of the AUC for glucose from baseline showed a dose‐related increase in the dose range from 8 to 48 mg in both stages. Together, this study indicated that in healthy Chinese subjects, this oral capsule containing 2 different insulin formulations was safe and well tolerated after a single‐dose administration. [ABSTRACT FROM AUTHOR]

The effect of the structure of a mucoadhesive, insulin-containing, polymeric hydrogel on the rate of hormone release was studied. It has been shown that a decrease in the pore size of the hydrogel leads to an increase in the rate of insulin release, which contributes to a reduction in the time to achieve a positive effect upon oral administration of the drug while maintaining the physiological pathway of hormone penetration of the blood through the liver. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL) standard chow group; high fat diet low carbohydrates group (HFD) and HFD plus daily oral 20U insulin gavage (HFD+INS). Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p

Abstract: Nanothickness encapsulation using a layer-by-layer technique has applications in several areas of diabetes research, including improved glucose sensors, islet cell transplantation and oral insulin delivery. We have fabricated microvesicles containing a fluorescence lifetime-based glucose sensing system, with bacterial glucose-binding protein as the glucose receptor. Such sensors are suitable for impregnation in the dermis as a ‘smart tattoo’ type of non-invasive glucose monitoring technology. Nanoencapsulation of islet cells is intended to alleviate the immediate blood-mediated inflammatory reaction which is responsible for early islet loss post-transplant. In an allogeneic diabetic mouse model, nanoencapsulated islets with phosporylcholine-modified polysaccharide coating, significantly extended survival of transplanted islets. In early studies aimed at formulating an effective oral insulin preparation, insulin-chitosan colloids coated with nanolayers of chitosan and heparin had enhanced acid stability and effectively lowered blood glucose in an animal model. [Copyright &y& Elsevier]

Diabetes mellitus (DM) results from defects in insulin secretion (type 1) or insulin resistance (type 2). Insulin is used to manage type 1 DM, and oral hypoglycemic agents are used to manage type 2 DM. These therapies are inconsistent in maintaining glycemic control and cause some severe adverse effects such as undue weight gain and hypoglycemia. New and appropriate therapies are needed to overcome these problems. Drugs that are in the pipeline include oral insulins for type 1 DM and incretin mimetics, incretin enhancers, gastric inhibitory peptides, amylin analogues, peroxisome proliferator-activated receptor-α/γ ligands, sodium-dependent glucose transporter inhibitors, and fructose 1,6-bisphosphatase inhibitors for type 2 DM. This article describes the mechanisms of action and relative advantages and disadvantages of the promising therapies [ABSTRACT FROM PUBLISHER]

Abstract: An oral insulin delivery system based on methyl-β-cyclodextrin (MCD) complexed insulin encapsulated polymethacrylic acid (PMAA) hydrogel microparticles was evaluated in this investigation. Poly(methacrylic acid)-chitosan-polyethylene glycol (PCP) microparticles were prepared by ionic gelation method. The insulin–MCD (IC) complex prepared was characterized by fluorescence spectroscopic and isothermal titration micro-calorimeteric (ITC) methods. MCD complexed insulin was encapsulated onto PCP microparticles by diffusion filling method. Loading and release properties of the complexed insulin from microparticles were evaluated under in vitro conditions. The effect of MCD complexation on the permeability of insulin was studied using Caco 2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. In vivo experiments were carried on streptozotocin induced diabetic rats to evaluate the efficacy of MCD complexed insulin encapsulated PCP microparticles to deliver insulin by the oral route. IC complex formation was established by fluorescence and ITC investigations. Insulin loading and release properties from the hydrogel matrix was rather unaffected by the MCD complexation. However MCD complexation was effective in enhancing insulin transport across Caco 2 cell monolayers, when applied in combination with the PMAA hydrogel system. Both insulin and MCD complexed insulin encapsulated PCP microparticles were effective in reducing blood glucose level in diabetic animal models. Cyclodextrin complexed insulin encapsulated hydrogel microparticles appear to be an interesting candidate for oral delivery of insulin. [Copyright &y& Elsevier]

Abstract: In this study, we report the biodistribution of aspart-insulin, a rapid-acting insulin analogue, following oral or subcutaneous (SC) administration to rats using the single-photon emission computed tomography (SPECT)/computed tomography (CT). Oral delivery of aspart-insulin was achieved using a pH-responsive nanoparticle (NP) system composed of chitosan (CS) and poly(γ-glutamic acid). The results obtained in the SPECT/CT study indicate that the orally administered aspart-insulin was absorbed into the systemic circulation, while the drug carrier (CS) was mainly retained in the gastrointestinal tract.Via the SC route, the peak aspart-insulin concentration in the peripheral tissue/plasma was observed at 20 min after injection. Within 3 h, half of the initial dose (ID) of aspart-insulin was degraded and excreted into the urinary bladder. In contrast, via oral delivery, there was constantly circulating aspart-insulin in the peripheral tissue/plasma during the course of the study, while 20% of the ID of aspart-insulin was metabolized and excreted into the urinary bladder. In the pharmacodynamic (PD) and pharmacokinetic (PK) evaluation in a diabetic rat model, the orally administered aspart-insulin loaded NPs produced a slower hypoglycemic response for a prolonged period of time, whereas the SC injection of aspart-insulin produced a more pronounced hypoglycemic effect for a relatively shorter duration. Finally, comparison of the PD/PK profiles of the orally administered aspart-insulin with those of the SC injection of NPH-insulin, an intermediate-acting insulin preparation, suggests the suitability of our NP system to be used as a non-invasive alternative for the basal insulin therapy. [Copyright &y& Elsevier]

Oral insulin is one of the most exciting areas of development in the treatment of diabetes because of its potential benefit in patient convenience, rapid insulinization of liver, adequate insulin delivery avoiding peripheral hyperinsulinaemia while potentially avoiding adverse effects of weight gain and hypoglycaemia. Growing evidence that earlier initiation of intensive insulin therapy produces sustained tight glycaemic control resulting in substantial delay in complications makes an effective oral insulin product even more vital for the management of patients with diabetes. Despite knowledge of this unmet medical need, oral delivery of insulin has been unsuccessful because of several barriers. For several decades, researchers have tried to develop oral insulin using various technologies without much clinical or commercial success. This review summarizes the development status of oral insulins which are publicly reported to be undergoing clinical studies. Currently, two oral insulin products are in an advanced stage of clinical development and first data from long-term therapy are expected to be available in the second half of 2010. [ABSTRACT FROM AUTHOR]

Nanoparticles prepared with a blend of a biodegradable polyester (poly(ℇ-caprolactone)) and a polycationic nonbiodegradable acrylic polymer (Eudragit® RS) have been used as a drug carrier for oral administration of a short-acting insulin analogue, aspart-insulin. Insulin-loaded nanoparticles, about 700 nm in diameter, encapsulated 97.5% of insulin and were able to release about 70% of their content in vitro in a neutral medium over 24 h. When administered orally to diabetic rats, insulin-loaded nanoparticles (50 IU/kg) decreased fasted glycemia for a prolonged period of time and improved the glycemic response to glucose in a time-dependent manner, with a maximal effect between 12 and 24 h after their administration. In parallel, plasma insulin levels increased. However, higher (100 IU/kg) and lower (25 IU/kg) doses of insulin did not exert any biological effect. It is concluded that polymeric nanoparticles composed of poly(ℇ-caprolactone)/Eudragit® RS are able to preserve the biological activity of the insulin analogue aspart-insulin; however, the postprandial peak suppression was prolonged more than 24 h by comparison with regular insulin working only 6–8 h. This effect may be explained by the monomeric configuration of aspart-insulin, which is probably better taken up by the intestinal mucosa than regular insulin. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:879–889, 2010 [ABSTRACT FROM AUTHOR]

For many decades, rigorous efforts have been made worldwide to develop a successful oral insulin-delivery system, which still remains an elusive goal. However, over the past few years, tremendous understanding has evolved in the development of biocompatible and biodegradable polymers, synthesis of nanopeptide delivery systems, bicompatibility and its cellular uptake mechanisms. With these advancements, efforts are being directed toward nanoparticle-based oral peptide-delivery systems. It is established that nanoparticles enhance oral bioavailability by facilitating insulin uptake via a transcellular or paracellular pathway. In this process, the particle also reaches the systemic circulation. Hence, biocompatibility and the half-life of the particles in the systemic circulation is an important aspect that needs to be looked into. In this review, the various approaches adopted for nanoparticle-based oral insulin delivery, uptake mechanisms, biocompatibility and bioavailability of the nanoparticle are discussed. INSETS: Examples of organic/inorganic materials used in …;Key issues. [ABSTRACT FROM AUTHOR]

Abstract: The potential utility of vitamin B12 carrier system for the oral delivery of conjugated peptides/proteins and enhancement of nanoparticles (NPs) transport has been demonstrated. The present study aims to optimize the effectiveness of VB12–NPs conjugates using different levels of cross-linking, linked with different VB12-coatings and evaluates in animal models to investigate an efficient insulin carrier. Amino alkyl VB12 derivatives suitable for oral delivery were synthesized at 5′hydoxy ribose and e-propionamide sites via carbamate and ester/amide linkages, and were coupled to succinic acid modified dextran NPs of varied cross-linking. VB12 binding was confirmed by XPS analysis, and was quantified by HPLC (4.0 to 5.7% w/w of NPs). These polydisperse NPs conjugates showed higher size, high insulin entrapment and faster insulin release with low levels of cross-linking. These VB12–NPs conjugates (150–300 nm) showed profound (70–75% blood glucose reductions) and prolonged (54 h) anti-diabetic effects with biphasic behaviour in STZ diabetic rats. NPs with the low levels of cross-linking were found to be superior carriers, and were more effective with VB12 derivatives of carbamate linkage. The pharmacological availability relative to SC insulin was found to be 29.4%, which was superior compared to NPs conjugate of ester linked VB12 (1.5 fold) and relatively higher cross-linked particles (1.1 fold). Further, the NPs carrier demonstrated a similar oral insulin efficacy in congenital diabetic mice (60% reduction at 20 h). Significant quantities of plasma insulin were found in both animal models (231 and 197 μIU/ml). At two investigated doses, the carrier system shows dose response. Pre-dosing with a large excess of free VB12 minimized the observed activity, indicating predominance of VB12 mediated uptake. It is concluded that VB12–dextran NPs conjugate is a viable carrier for peroral insulin delivery to treat diabetics. [Copyright &y& Elsevier]

Abstract: Background:: Several advances in insulin delivery systems and devices have been made in recent years. Objective:: This article summarizes study findings on recent advances and emerging insulin delivery systems in various stages of development. Methods:: Materials used for this article were identified through a search of MEDLINE from 1993 to 2006. English-language articles were chosen using the search terms transdermal delivery system, inhaled insulin, and oral insulin. Results:: These developments are intended to enhance patient compliance with insulin therapy to achieve tighter glycemic control and thereby prevent or delay the onset of diabetes mellitus (DM)-related complications. Recently, the US Food and Drug Administration provided regulatory approval for recombinant human insulin for inhalation; availability of this first inhaled insulin is expected in the near future. Several other inhaled insulin products are now in clinical trials. Also available are the insulin pump and insulin pen, which can facilitate self-administration for some patients. Research is under way to develop an insulin tablet that is coated so it resists breakdown in the digestive tract. Intranasal and transdermal delivery systems are also being investigated. Conclusion:: Progress has been made in the development of alternative delivery routes for insulin therapy. Clinicians who provide DM care can look forward to the availability of more options in insulin delivery systems to help their patients meet the challenges of DM management. [Copyright &y& Elsevier]

Abstract: Cell-penetrating peptide (CPP) was linked to insulin to form insulin–CPP hybrids. The intestinal absorption efficiency of CPP hybridized insulin was 6–8 times increased compared to normal insulin as tested on Caco-2 cell monolayer, a widely used in vitro model for intestinal absorption. Insulin–CPP hybrid transportation seemed to be through an active and transcytosis-like mechanism. Importantly, insulin in hybrids kept intact after they passed through the Caco-2 cell monolayer. This study provides a new clue for oral insulin development. [Copyright &y& Elsevier]

In normal humans, blood glucose and insulin are maintained within a narrow range despite wide variations in physical activity and dietary intake. At present, reproducing this pattern is an impossible task in type 1 diabetes and extremely difficult in type 2 DM. New approaches using novel insulin analogs and routes of administration, attempting to replicate physiological insulin secretion in diabetic patients, are improving the profiles of glucose levels and, thus, the quality of life. Ultra-short-acting insulin analogues and ultra-long-acting analogues are being used for prandial and basal effects with better results, lower prevalence of hypoglycemia, and, hopefully, fewer chronic complications. Non-invasive routes of administration are being developed. The most promising appears to be inhaled insulin according to studies demonstrating excellent control, apparently without significant side effects, although in relatively short-term trials. Longer-term studies to assure the safety are still necessary before recommending its extended use. This is an extensive, up-to-date review of recent advances in insulin therapy. [Copyright &y& Elsevier]

The aim of our study was to examine the absorption of insulin from the gastrointestinal (GI) tract, using a novel oral formulation—adding a delivery agent SNAC (sodium N-[8-(2-hydroxybenzoyl)amino] caprylate) in combination with insulin. Capsules containing insulin and SNAC, in various combinations, were administered orally, as a single dose, to 12 non-diabetic subjects and four control subjects (receiving SNAC or insulin only) in order to assess its biological effect and safety. Plasma glucose levels, insulin and C-peptide concentrations, as well as SNAC levels, were determined, at timed intervals up to 4 h. In all cases, a glucose-lowering effect was demonstrated, preceded by an increase in plasma insulin levels. The nadir of plasma glucose levels appeared after 30–50 min, following the ingestion of the mixture. The plasma insulin levels were found to parallel the blood SNAC levels. Plasma C-peptide levels were suppressed by the lowered glucose levels achieved concurrent with the increasing amount of exogenous insulin absorbed, indicating that the secretion of endogenous hormone was partially abolished. There were no biological effects regarding blood glucose levels upon administration of SNAC or insulin when given alone. No adverse effects were detected during the trial or several weeks after the trial. Insulin in combination with a novel delivery agent, SNAC, given orally, is absorbed through the GI tract in a biologically active form. This was demonstrated by a glucose lowering effect of the mixture as well as a suppression of an endogenous insulin secretion. Diabet. Med. 21, 354 –357 (2004) [ABSTRACT FROM AUTHOR]

SUMMARY Our earlier investigations have demonstrated a critical difference in the efficacy of orally administered porcine compared to human or mouse insulin (no effect) in preventing type I diabetes in two distinct experimental models. Based on these findings one has to assume that certain insulins might not be suitable for the induction of oral ‘tolerance’/bystander suppression, which might be one cause for recent failures in human oral antigen trials. Here we demonstrate that coupling to the non-toxic subunit of cholera toxin (CTB) can abolish these differences in efficacy between human and porcine insulin. As expected, an added benefit was the much smaller oral antigen dose required to induce CD4[sup +] insulin-B specific regulatory cells that bystander-suppress autoaggressive responses. Mechanistically we found that uptake or transport of insulin–CTB conjugates in the gut occurs at least partially via binding to GM-1, which would explain the enhanced clinical efficacy. Both B chains bound well to major histocompatibility complex (MHC) class II, indicating comparable immunological potential once uptake and processing has occurred. Thus, our findings delineate a pathway to overcome issues in oral antigen choice for prevention of type I diabetes. [ABSTRACT FROM AUTHOR]

Summary Aim: Although the oral route for insulin delivery is the most convenient, directly administered oral insulin is degraded by proteolytic enzymes in the gastrointestinal (GI) tract. Polylactide was prepared in order to microcapsulate the insulin to avoid the enzymes in the GI. The physical characteristics and therapeutic possibilities of polylactide microcapsulated insulin (PLA-MCI) were studied in vivo and in vitro. Methods: PLA-MCI was prepared by the two-step method of emulsion and solvent extraction. Its morphologic character was observed by scanning electron microscopy (SEM). The insulin release profile was determined in vitro by insulin measurement and in vivo by blood glucose measurement after the force-feeding of 66 diabetic rats. Results: When the microcapsule was spherical in shape (diameter 1.5–2.0μm) the entrapment efficiency of insulin was 90% and the loading rate was 10% (W/W). The PLA-MCI (which contained 3.0 units of insulin/mg of PLA) had peak release rates of 65–74% over 6–8 h in phosphate buffer. The same dose of PLA-MCI (insulin 2.5 mg) led to decreased responses (from 28% to 68% of control blood glucose levels) in the level of blood glucose in 32 rats which had not fasted after they had been force-fed. When 1.2, 1.8, 2.2 and 3.0 mg of insulin + PLA-MCI was administered to eight diabetic rats, their blood glucose levels decreased by 28%, 36%, 54% and 78%, respectively. Conclusions: PLA microcapsules are capable of protecting insulin from degradation by the proteolytic enzymes in the GI and of alleviating hyperglycaemia for a prolonged period of time in diabetic rats. It may therefore be considered as a new carrier for oral insulin. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Induction of tolerance to insulin is achievable in animal models of Type I (insulin-dependent) Diabetes mellitus by oral treatment with this hormone, which can lead to prevention of the disease. In the Diabetes Prevention Trial of Type I diabetes (DPT-1), oral insulin is given with the aim of preventing disease insurgence. We investigated whether if given at diagnosis of Type I diabetes in humans, oral insulin can still act as a tolerogen and therefore preserve residual beta-cell function, which is known to be substantial at diagnosis. Methods. A double-blind trial was carried out in patients (mean age ± SD: 14 ± 8 years) with recent-onset Type I diabetes to whom oral insulin (5 mg daily) or placebo was given for 12 months in addition to intensive subcutaneous insulin therapy. A total of 82 patients with clinical Type I diabetes ( < 4 weeks duration) were studied. Basal C peptide and glycated haemoglobin were measured and the insulin requirement monitored every 3 months up to 1 year. Insulin antibodies were also measured in 27 patients treated with oral insulin and in 18 patients receiving placebo at the beginning of the trial and after 3, 6 and 12 months of treatment. Results. The trial was completed by 80 patients. Overall and without distinction between age at diagnosis, at 3, 6, 9 and 12 months baseline mean C-peptide secretion in patients treated with oral insulin did not differ from that of those patients treated with placebo. In patients younger than 15 years a tendency for lower C-peptide values at 9 and 12 months was observed in the oral insulin group. Insulin requirement at 1 year was similar between the two groups as well as the percentage of glycated haemoglobin. Finally, IgG insulin antibodies were similar in the two groups at each time point. Conclusion/interpretation. The results of this study indicate that the addition of 5 mg of oral insulin does not modify the course of the disease in the first year after diagnosis and probably does not statistically affect the humoral immune response against insulin. [Diabetologia (2000) 43: 1000–1004] [ABSTRACT FROM AUTHOR]

Arabinoxylans (AX) covalent gels are little affected by pH changes and fermentable by colonic microbiota, which make them suitable for insulin oral administration and colon‐targeted delivery. In this work, the tailoring of insulin aggregates size using glutamic acid and their loading in AX microspheres (2%w/v) prepared by triaxial electrospray is presented. Dynamic light scattering showed that insulin‐glutamic acid aggregates are reversible under intestinal conditions. AX microspheres presented a spherical shape, a mean diameter of 233 μm, a heterogeneous microstructure as shown by scanning electron microscopy, and a homogeneous distribution of insulin aggregates as observed by confocal laser scanning microscopy. In this AX‐insulin system, 20% of insulin is released under simulated gastrointestinal pH conditions, indicating that most of the insulin stays into the microspheres, available for colonic release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47960. [ABSTRACT FROM AUTHOR]

Nature is a huge enigma, having an inexhaustible plate of mysteries to fill man's insatiable thirst of knowledge. Two such products of nature, alginate and chitosan, have potential to be used in wide variety of encapsulated drug formulations. Diabetes Mellitus is a multi-factorial and multi-consequential chronic metabolic disorder with the hallmark feature of hyperglycaemia. Current therapy through oral anti-diabetic drugs and subcutaneous administration of insulin suffers from serious disadvantages of occasional hypoglycaemia due to unmonitored dosage and lipoatrophy. These approaches don't mimic normal physiological pattern of insulin release. Thus, bio-compatible oral insulin formulations, if made possible, would prove to be a boon. This preliminary study included 100IU insulin encapsulated in 1% CS (in 5% acetic acid) + 2% ALG (in 2% CaCl2). Insulin encapsulated CS ALG beads were prepared by simple extrusion method. At pH 7.4 (intestinal), swelling ratio of coated beads is significantly higher indicating that this formulation can be used for intestinal peptide drug delivery. SEM gave an average size of 30-50mm.Also, shift of characteristic bond peaks in FTIR spectra of CS/ALG/INS loaded beads is indicative of insulin encapsulation. Nitrogen in EDX results validates the interaction between chitosan and alginate, hence, the blending. Release rate graph suggests, in 9hrs maximum cumulative release achieved was near to 20%. Entrapment Efficiency of beads was calculated as 39%. Therefore, release was about 50%. The best linearity, with R2=0.85, was found in Higuchi's equation plot indicating the release of drug from matrix as a square root of time dependent process based on Fidrian diffusion. Korsmeyer Peppas model, n>0.89, suggest release mechanism to be Super Case II Transport. [ABSTRACT FROM AUTHOR]