scholarly journals Ionic liquids for oral insulin delivery

2018 ◽  
Vol 115 (28) ◽  
pp. 7296-7301 ◽  
Author(s):  
Amrita Banerjee ◽  
Kelly Ibsen ◽  
Tyler Brown ◽  
Renwei Chen ◽  
Christian Agatemor ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Oral Delivery ◽  
Patient Adherence ◽  
Oral Insulin ◽  
Delivery Vehicle ◽  
Oral Gavage ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Insulin Formulation

With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3–10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.

LAYANAN PESAN SINGKAT PENGINGAT MENINGKATKAN KEPATUHAN MINUM OBATPASIEN DIABETES MELITUS DI RSUD ULIN BANJARMASIN

2017 ◽  
Vol 1 (1) ◽  
pp. 57
Author(s):  
Riza Alfian
Keyword(s):  
Blood Glucose ◽  
Medication Adherence ◽  
Short Message Service ◽  
Patient Adherence ◽  
Fasting Blood Glucose ◽  
Short Message ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Message Service ◽  
Diabetes Melitus

Diabetes melitus is one ofthe metabolic disorders with characteristic hyperglycemia that occurs due to abnormal insulin secretion, insulin resistance or both. The non adherence patients of taking antidiabetic drugs are the main factors that could cause high blood glucose levels, so it is necessary an intervention to achievedoutcome therapy desired. Giving of short message service reminder intervention in diabetes mellitus patients was expected to improved the medication adherence and achieved normal blood glucose levels.This study was conducted to determine the effect of a short message service reminder on medication adherence of ambulatory diabetes melitus patients in Ulin General Hospital Banjarmasin.This study was conducted with quasi-experimental design,the data were taken prospectively during May to June, 2014. The subjects were ambulatory diabetes melitus patients in Ulin General Hospital Banjarmasin who had received oral antidiabetic drugs. Subject who met the inclusion and exclusion criteria were 39 patients and had given an intervention for seven days. The data collected by interviews and pill counting on filling sheet. The blood glucose levels data was taken from their medical records.The result showed that giving of a short message service reminder intervention improve patient adherence (p<0,05). Fasting blood glucose level and blood glucose level two hours post prandial have decreased significantly (p<0,05). There were correlation between the patient adherence and the decreasing in fasting blood glucose levels (p=0,050; r=0,316) and blood glucose two hours post prandial levels (p=0,010; r=0,040).Based on these result, it can be concluded that the giving of short message service reminder in diabetes melitus patientshas been improved patient adherence.

scholarly journals Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1517 ◽  
Author(s):  
Kai Wang ◽  
Yu Su ◽  
Yuting Liang ◽  
Yanhui Song ◽  
Liping Wang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Enzymatic Activity ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

scholarly journals Glycemic Variability in Diabetes Increases the Severity of Influenza

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Rebecca J. Marshall ◽  
Pornthida Armart ◽  
Katina D. Hulme ◽  
Keng Yih Chew ◽  
Alexandra C. Brown ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glycemic Variability ◽  
Endothelial Barrier ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Severe Influenza ◽  
Increased Risk ◽  
History Of

ABSTRACT People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus. IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.

scholarly journals “Oil-soluble” Reversed Lipid Nanoparticles for Oral Insulin Delivery

2020 ◽  
Author(s):  
Tao Wang ◽  
Dongqin Quan
Keyword(s):  
Oral Absorption ◽  
Insulin Delivery ◽  
Lipid Nanoparticles ◽  
Oral Insulin ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Transmission Electron ◽  
Insulin Solution

Abstract Background In this study, we aimed to design a novel oral insulin delivery system, named “oil-soluble” reversed lipid nanoparticles (ORLN), in which a hydrophilic insulin molecule is encapsulated by a phospholipid (PC) shell and dissolved in oil to prevent the enzymatic degradation of insulin. ORLN was characterized by transmission electron microscopy and dynamic light scattering. Results In vitro enzymatic stability studies showed higher concentrations of insulin in cells incubated with ORLN-encapsulated insulin than in those incubated with free insulin solution in artificial intestinal fluid (pH 6.5). The protective effect of ORLN was attributed to its special release behavior and the formulation of the PC shell and oil barrier. Furthermore, an in vivo oral efficacy study confirmed that blood glucose levels were markedly decreased after ORLN administration in both healthy and diabetic mice. In vivo pharmacokinetic results showed that the bioavailability of ORLN-conjugated insulin was approximately 28.7% relative to that of the group subcutaneously administered with an aqueous solution of insulin, indicating enhanced oral absorption. Conclusions In summary, the ORLN system developed here shows promise as a nanocarrier for improving the oral absorption of insulin.

In vitro and in vivo anti-diabetic activity of Citrullus colocynthis pulpy flesh with seeds hydro-ethanolic extract

2020 ◽  
Vol 17 (2) ◽  
Author(s):  
Aymen Owais Ghauri ◽  
Saeed Ahmad ◽  
Tayyeba Rehman
Keyword(s):  
Blood Glucose ◽  
Normal Control ◽  
Ethanolic Extract ◽  
Negative Control ◽  
Antioxidant Potential ◽  
Blood Glucose Monitoring ◽  
Glucose Levels ◽  
Blood Glucose Levels

AbstractBackgroundDiabetes is the one of the leading cause of morbidity and mortality. Traditionally phytotherapy is widely being used for diabetes treatment and highly valued. Citrus colocynthis has known anti-diabetic potential. However, anti-diabetic potential of hydro-ethanolic extract of C. colocynthis pulpy flesh with seeds is not reported yet.MethodsThe extract of C. colocynthis pulpy flesh with seeds was done by maceration method using 70% ethanol. To evaluate anti-diabetic and antioxidant potential of the seeded fruit in vitro, α-glucosidase and DPPH inhibition assays was done, respectively. In vivo study used streptozotocin (STZ) induced diabetes model of rats. Rats were randomized in five groups i. e. normal control, negative control, standard control, C. colocynthis 150 and 300 mg/kg. STZ was administered to all groups except normal control. After wards, plant extract and glibenclamide is continued for 14 days. Blood samples were collected from rat tail vein daily and from Cardiac puncture at the end of study. The blood glucose levels were monitored daily by using one-touch blood glucose monitoring system. The blood glucose level was monitored on 0, 1st, 5th, 8th, 11th, and 14th day of induction.ResultsHydro-ethanolic extract of C. colocynthis pulpy flesh with seeds was able to decolorize DPPH and therefore possess antioxidant potential, continuous administration for 14 days showed a marked decrease in serum glucose levels (p 0.01) it is found to be somewhat less effective as glibenclamide (standard control) (p 0.001). A time-dependent decrease in blood glucose levels was observed (351.3 ± 4 to 258 m/kg).ConclusionHydro-ethanolic extract of C. colocynthis pulpy flesh with seeds lowered the serum triglyceride and cholesterol levels in diabetic rats significantly as compared to negative control. The hypoglycemic effect of hydro-ethanolic extract of C. colocynthis pulpy flesh with seeds is may be due to α-glucosidase inhibition potential.

scholarly journals Mucin-Grafted Polyethylene Glycol Microparticles Enable Oral Insulin Delivery for Improving Diabetic Treatment

2020 ◽  
Vol 10 (8) ◽  
pp. 2649 ◽  
Author(s):  
Momoh A. Mumuni ◽  
Ugwu E. Calister ◽  
Nafiu Aminu ◽  
Kenechukwu C. Franklin ◽  
Adedokun Musiliu Oluseun ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Oral Delivery ◽  
Subcutaneous Administration ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Insulin Solution ◽  
Diabetic Treatment ◽  
Short Time

In this study, different ratios of mucin-grafted polyethylene-glycol-based microparticles were prepared and evaluated both in vitro and in vivo as carriers for the oral delivery of insulin. Characterization measurements showed that the insulin-loaded microparticles display irregular porosity and shape. The encapsulation efficiency and loading capacity of insulin were >82% and 18%, respectively. The release of insulin varied between 68% and 92% depending on the microparticle formulation. In particular, orally administered insulin-loaded microparticles resulted in a significant fall of blood glucose levels, as compared to insulin solution. Subcutaneous administration showed a faster, albeit not sustained, glucose fall within a short time as compared to the polymeric microparticle-based formulations. These results indicate the possible oral delivery of insulin using this combination of polymers.

Formulation and evaluation of anti-diabetic activity of repaglinide nanosuspension

2020 ◽  
Vol 8 (2) ◽  
pp. 17-21
Author(s):  
Hemalatha S ◽  
Monisha J
Keyword(s):  
Blood Glucose ◽  
Glucose Level ◽  
Clinical Efficacy ◽  
Oral Delivery ◽  
Vascular Tissue ◽  
Postprandial Glucose ◽  
Postprandial Blood Glucose ◽  
Particle Size Reduction ◽  
Glucose Levels ◽  
Blood Glucose Levels

Diabetes is one of those metabolic disorders that are typically characterized by an increase in blood glucose level, glycosuria and ketonemia. This widely spread disease and its complications result in thickening of vascular tissue, PVD, neuropathy and retinopathy. Repaglinide is the first member of the newer class of drugs that are designed to lower the postprandial glucose. The most prevalent problem faced by those drugs are very low solubility and thereby causing the oral delivery very inefficient leading to low bioavailability and improper dose and release proportionality. Research attempts are being put towards enhancing the oral bioavailability of repaglinide kind of lipophilic drugs to improve the clinical effect. Out of those methods to improve the solubility and bioavailability, Nano suspensions have been a promising method to facilitate the above problem. Nano suspensions can be applied to enhance the solubility of Repaglinide too. So, in this research, Repaglinide particle size reduction has been performed, and nanosuspensions were tested for their clinical efficacy invivo. A nanoprecipitation method was developed to prepare Repaglinide nanosuspension using poloxamer as a stabilizer. The prepared formulations had been tested for the clinical efficacy invivo in albino Wistar rats. The results showed that the nanosuspensions have been very efficient in lowering the postprandial blood glucose levels and also facilitated the consistent release of the drug, which is evident from the constant lowering of glucose level. The prepared nanosuspensions showed a very potent and found to clinically efficient compared to the pure drug and drug suspensions.

Determination the limit of postprandial blood glucose increase and the metabolism of acetylated wheat starch on healthy mice

2019 ◽  
pp. 15-22
Author(s):  
Khoa Bao Chau Thai ◽  
Huu Tien Nguyen ◽  
Huu Dung Tran
Keyword(s):  
Blood Glucose ◽  
Wheat Starch ◽  
Postprandial Blood Glucose ◽  
Control Group ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Treatment Of Diabetes ◽  
Resistant Starches

Introduction: Nowadays, resistant starches are interested as a supplement food by effecting on the limit of postprandial blood glucose increase and supporting for the diabetes treatment. Recently, we have semisynthesized the acetylated wheat starch (AWS) oriented for supporting the treatment of diabetes mellitus, which is the RS4 formed by chemical structure modification. AWS has been proved itself to show strong resistance to amylase activity in-vitro as well as to be safety in-vivo. Materials and Methods: In this study, we continued to evaluate AWS’s ability to limit postprandial blood glucose increase and determined shortchain fatty acids (SCFAs) metabolized from AWS in the gastrointestinal tract of healthy mice by HPLC. Results: the mice fed AWS exhibited a very limited increase in blood glucose levels and remained stable for 2 hours after meals comparing with the control group (mice fed natural wheat starch) (NWS). Simultaneously, the content of SCFAs produced in the caecum of the mice fed AWS was significantly higher than mice fed NWS, especially with acetic and propionic acids by 28% and 26%, respectively. Conclusion: AWS has been shown to limit postprandial hyperglycemia in mice effectively through the resistance to amylase hydrolysis in the small intestine. When going into the caecum, it is fermented to form SCFAs that provide a part of the energy for the body’s activities and to avoid rotten fermentation causing digestive disorders, which are inherent restrictions of normal high cellulose and fiber food. Key words: acetylated wheat starch, natural wheat starch, SCFA, blood glucose

Comparative effects of phlorizin and phloretin on glucose transport in the cat kidney

1962 ◽  
Vol 203 (6) ◽  
pp. 975-979 ◽  
Author(s):  
Stephen S. Chan ◽  
William D. Lotspeich
Keyword(s):  
Blood Glucose ◽  
Glucose Transport ◽  
Renal Tubule ◽  
Tubular Reabsorption ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Dog Kidney ◽  
Glucose Carrier

The net tubular reabsorption of glucose (TG) was measured simultaneously in both kidneys of the cat before, during, and after the infusion of small amounts of phlorizin and phloretin at constant rates into one renal artery. Experiments were performed at endogenous and elevated blood glucose levels. The results show that phlorizin blocks glucose transport across the renal tubule at concentrations in renal blood and tissue in the range of 10–5 to 10–7 m. These estimates agree with those for dog kidney in vivo and hamster small intestine in vitro. In addition to this high affinity of phlorizin for the tubular glucose carrier, the experiments also reveal the easily dissociable nature of the phlorizin carrier complex. When blood glucose is elevated the TG is even more sensitive to small concentrations of phlorizin. At all blood glucose levels the aglucone, phloretin, is at least ten times less effective in inhibiting TG than phlorizin itself. These findings are discussed in relation to critical groupings in the phlorizin molecule.

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