Synthesis, Characterization and in vivo Evaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin

2019 ◽  
Vol 9 (3) ◽  
pp. 248-263 ◽  
Author(s):  
Ashish K. Parashar ◽  
Preeti Patel ◽  
Arun K. Gupta ◽  
Neetesh K. Jain ◽  
Balak Das Kurmi
Keyword(s):  
Blood Glucose ◽  
Drug Release ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Albino Rats ◽  
Sustained Delivery ◽  
In Vivo Evaluation ◽  
Hemolytic Toxicity

Background: The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin. Methods: For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared. Results: PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances. Conclusion: Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.

scholarly journals Bioequivalence Assessment of Metformin Tablet Formulations of Bangladesh

2014 ◽  
Vol 6 (3) ◽  
pp. 581-588
Author(s):  
M. A. Islam ◽  
A. Islam ◽  
M. R. I. Khan ◽  
R. Sharmin ◽  
M. I. I. Wahed ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Diabetic Rats ◽  
In Vivo Evaluation ◽  
Glucose Levels ◽  
Drug Content ◽  
Oral Antidiabetic ◽  
Metformin Hcl

Six marketed oral antidiabetic metformin tablets in Bangladesh have been studied for their drug content, release profile and glucose lowering capacities. This sort of study is a good indicator for in vivo evaluation of the quality of an oral antidiabetic preparation. Marketed preparations of metformin-HCl from different manufacturers were randomly chosen for this study. The drug content was within the United State Pharmacopoeia (USP) specified limit (95-105%) in all cases. The blood glucose levels were investigated in streptozotocin-induced diabetic rats (SIDRs) after 5 hours of single dose (110 mg/kg body weight) treatment of the products; significantly (p<0.05) reduced blood glucose level by 58.1, 53.2, 50.8, 77.0, 72.9 and 49.1%, respectively; which were consistent with antihyperglycemic effects of standard metformin-HCl (71.3%). All the products were found to be qualified in lowering blood glucose level. It may be inferred that the metformin-HCl tablets of Bangladeshi manufacturers complies with the standard specifications for drug contents, dissolution and antihyperglycemic properties.© 2014 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi: http://dx.doi.org/10.3329/jsr.v6i3.19290 J. Sci. Res. 6 (3), 581-588 (2014)

scholarly journals Evaluation of Aqueous Extract of Alphonsea sclerocarpa for in vivo and in vitro Antidiabetic Potentials in Wistar Rats

2021 ◽  
Vol 70 (2) ◽  
Author(s):  
Ravi Shankar N ◽  
Ram Kishore ◽  
Puranik SB
Keyword(s):  
Blood Glucose ◽  
Glucose Uptake ◽  
Aqueous Extract ◽  
Insulin Level ◽  
Antidiabetic Activity ◽  
Albino Rats ◽  
Oral Glucose ◽  
In Vivo Evaluation

The purpose of current investigation was to investigate in vivo and in vitro anti-diabetic potentials of aqueous extract of Alphonsea sclerocarpa leaves against alloxan induced diabetes in albino rats. Two in vivo and one in vitro methods were performed for the evaluation of aqueous extract for antidiabetic activity. For in-vivo evaluation, diabetes was induced in albino rats by administering a single dose of alloxan. The study was designed to test the acute effect of aqueous extract of Alphonsea sclerocarpa (AEAS) to reduce blood glucose in OGTT. The chronic study of 21 days was performed against diabetic rats and blood glucose was determined at 1st , 7 th, 14th and 21st day. In chronic in vivo study, serum parameters insulin, urea, creatinine, total cholesterol, triglycerides, ALT and AST were also estimated at 21st day to determine the effects of aqueous and aqueous extracts on complications of diabetes mellitus. Glucose uptake by hemidiaphragm assay was performed to test the ability of extract to utilize glucose. In Oral Glucose Tolerance Test, standard glibenclamide and aqueous extract (200mg/kg and 400mg/kg) treated animals have shown significant reduction in blood glucose at 90 mins but at 120 mins. In chronic model the aqueous extract effectively reduced blood glucose levels (P<0.001) at 14th and 21st day of study in therapeutic groups and effect was comparable to that of standard. The extract could also significantly (P<0.001) reduce concentrations of SGOT, triglycerides, cholesterol and urea in serum and significantly (P<0.001) increased the insulin level in blood which proves beneficial effects of the extract in diabetes. The change in concentrations of SGPT and urea were less significant (P>0.01). The presence of extract in glucose uptake assay could significantly increase utilization of the glucose by rat hemidiaphragm. The aqueous extract of Alphonsea sclerocarpa possess significant antidiabetic properties against alloxan induced diabetic animals.

Antidiabetic and protective effects of the aqueous extract of Arbutus unedo L. in streptozotocin-nicotinamide-induced diabetic mice

2018 ◽  
Vol 15 (3) ◽  
Author(s):  
Hanae Naceiri Mrabti ◽  
Karima Sayah ◽  
Nidal Jaradat ◽  
Faouzi Kichou ◽  
Abdelaziz Ed-Dra ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Aqueous Extract ◽  
Diabetic Mice ◽  
Antidiabetic Effect ◽  
Arbutus Unedo

Abstract Background Diabetes mellitus (DM) is currently a major health problem and the most common chronic disease worldwide. Traditional medicinal plants remedies remain a potential adjunct therapy to maintain better glycemic control while also imparting few side-effects. Arbutus unedo L. has been traditionally used to manage several diseases including diabetes. This study was undertaken to contribute the validation of the traditional use of Arbutus unedoL. (Ericaceae) in the treatment of diabetes. Methods In-vitro antidiabetic effect of the A. unedo roots aqueous extract was conducted using α-glucosidase and α-amylase assays. While in-vivo antidiabetic activity was conducted using streptozotocin-nicotinamide (STZ-NA) induced diabetic mice. Diabetic animals were orally administered the aqueous extract in 500 mg/kg of body weight to assess the antidiabetic effect. The blood glucose level and body weight of the experimental animals were monitored for 4 weeks. In addition, the histopathological examination of the treated mice pancreas was also conducted to observe the changes of β-cells during the treatment process. Results The extract produced a significant decrease in blood glucose level in diabetic mice. This decrease was equivalent to that which observed in mice treated with a standard after 2–4 weeks. In addition, the plant extract exhibited a potent inhibitory effect on α-amylase and α-glucosidase activity with IC50 values of 730.15±0.25 μg/mL and 94.81±5.99 μg/mL, respectively. Moreover, the histopathologic examination of the pancreas showed a restoration of normal pancreatic islet cell architecture which observed in the diabetic mice treated with plant extract. Conclusions The aqueous A. unedo roots extract has a significant in vitro and in vivo antidiabetic effects and improves metabolic alterations. The revealed results justify its traditional medicinal use.

scholarly journals IN VIVO AND IN VITRO EVALUATION OF TEPHROSIA CALOPHYLLA FOR ANTI-DIABETIC PROPERTIES

2018 ◽  
Vol 10 (6) ◽  
pp. 138
Author(s):  
Ramesh C ◽  
Prameela Rani A
Keyword(s):  
Blood Glucose ◽  
Total Cholesterol ◽  
Inhibitory Activity ◽  
Methanol Extract ◽  
Control Group ◽  
Albino Rats ◽  
In Vivo Evaluation ◽  
Ic50 Values

Objective: The objective the present work was to investigate in vivo and in vitro anti-diabetic potentials of methanol extract of Tephrosia calophylla against alloxan-induced diabetes in albino rats.Methods: For in vivo evaluation, diabetes was induced in albino rats by administering a single dose of alloxan. The study was designed to test the acute effect of methanol extract of Tephrosia calophylla (TCME) to reduce blood glucose in OGTT. The chronic study of 21 d was performed against diabetic rats and blood glucose was determined at 1st, 7th, 14th and 21st day. In chronic in vivo study, serum concentrations of insulin, urea, creatinine, total cholesterol, triglycerides, ALT and AST were also estimated at 21st day. The in vitro α-glucisidase inhibitory activity and α-amylase inhibitory activity were performed and IC50 values of the extract was determined. The glucose uptake by rat hemidiaphragm model was also used test potentials of the extract to increase utilization of the glucose by tissues.Results: In OGTT, standard glibenclamide and TCME at 400 mg/kg treated animals have shown significant reduction in blood glucose at 90 min but at 120 min, blood glucose level (BGL) was significantly reduced in glibenclamide and TCME at 200 mg/kg and 400 mg/kg treated animals compared to diabetic control group. In chronic modelthe methanol extract effectively reduced blood glucose levels (P<0.001) at 14 th and 21st day of study in therapeutic groups and effect was comparable to that of standard. The extract could also significantly (P<0.001) reduce concentrations of SGOT, triglycerides (TGs), Total cholesterol (TC) and urea in serum and significantly (P<0.001) increased the insulin level in blood which proves beneficial effects of the extract in diabetes. The change in concentrations of SGPT and urea were less significant (P>0.01). In vitro studies, against both glucosidae and  amyalase inhibitory activities, extract has shown significant IC50 values and it also enhanced glucose utilization by rat hemidaphragm.Conclusion: The results obtained from the present study suggest that, the methanol extract of Tephrosia calophylla possess significant in vivo anti-diabetic properties against alloxan induced diabetes in rats. The results also suggests that, TCME also possess the significant in vitro anti-dabetic potentials.

Preparation and Evaluation of Glipizide Tablets Containing both Enhanced and Sustained Release Solid Dispersions

1970 ◽  
Vol 2 (4) ◽  
pp. 714-725
Author(s):  
Adel M. Aly ◽  
Ahmed S. Ali
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Solid Dispersions ◽  
Solvent Evaporation ◽  
In Vivo Studies ◽  
Solvent Evaporation Method ◽  
Evaporation Method ◽  
Tablet Formulations

: Glipizide (GZ) is an oral blood-glucose-lowering drug of the sulfonylurea class characterized by its poor aqueous solubility. Aiming for the production of GZ tablets with rapid onset of action followed by prolonged effect; GZ-Polyethylene glycol (PEG 4000 and 6000) solid dispersions with different ratios, (using melting and solvent evaporation method), as well as, coprecipitate containing GZ with polymethyl-methacrylate (PMMA) were prepared. Four tablet formulations were prepared containing; a) GZ alone, b) GZ: PEG6000, 1:10, c) GZ:PMMA 1:3, and, d)both GZ:PEG6000 1:10 and GZ:PMMA 1:3. The solvent evaporation method showed more enhancement of GZ solubility than the melting one, and this solubilizing effect increased with PEG increment. Generally, PEG6000 showed more enhancement of dissolution than PEG4000 especially at 1:10 drug: polymer ratio (the most enhancing formula). Also, the prepared tablet formulations showed acceptable physical properties according to USP/NF requirements. The dissolution results revealed that tablets containing PEG6000 (1:10) have the most rapid release rate, followed by the formula containing both PEG6000 and PMMA, while that including PMMA alone showed the slowest dissolution rate. Moreover, In-vivo studies for each of the above four formulations, were performed using four mice groups. The most effective formula in decreasing the blood glucose level, through the first 6 hours, was that containing GZ and PEG6000, 1:10. However, formula containing the combination of enhanced and sustained GZ was the most effective in decreasing the blood glucose level through 16 hours. Successful in-vitro in-vivo correlations could be detected between the percent released and the percent decreasing of blood glucose level after 0.5 hours.

Design and In vivo Evaluation of Palonosetron HCl Mouth Dissolving Films in the Management of Chemotherapy-Induced Vomiting

2017 ◽  
Vol 10 (6) ◽  
pp. 3929-3936
Author(s):  
Y. Srinivasa Rao ◽  
K. Adinarayana Reddy
Keyword(s):  
Drug Release ◽  
Patient Compliance ◽  
Onset Of Action ◽  
In Vivo Evaluation ◽  
Disintegration Time ◽  
In Vitro Drug Release ◽  
Surface Ph ◽  
Drug Content

Fast dissolving oral delivery systems are solid dosage forms, which disintegrate or dissolve within 1 minute in the mouth without drinking water or chewing. Mouth dissolving film (MDF) is a better alternate to oral disintegrating tablets due to its novelty, ease of use and the consequent patient compliance. The purpose of this work was to develop mouth dissolving oral films of palonosetron HCl, an antiemetic drug especially used in the prevention and treatment of chemotherapy-induced nausea and vomiting. In the present work, the films were prepared by using solvent casting method with various polymers HPMC E3, E5 & E15 as a film base synthetic polymer, propylene glycol as a plasticizer and maltodextrin and other polymers. Films were found to be satisfactory when evaluated for thickness, in vitro drug release, folding endurance, drug content and disintegration time. The surface pH of all the films was found to be neutral. The in vitro drug release of optimized formulation F29 was found to be 99.55 ± 6.3 7% in 7 min. The optimized formulation F29 also showed satisfactory surface pH, drug content (99.38 ± 0.08 %), disintegration time of 8 seconds and good stability. FTIR data revealed that no interaction takes place between the drug and polymers used in the optimized formulation. In vitro and in vivo evaluation of the films confirmed their potential as an innovative dosage form to improve delivery and quick onset of action of Palonosetron Hydrochloride. Therefore, the mouth dissolving film of palonosetron is potentially useful for the treatment of emesis disease where quick onset of action is desired, also improved patient compliance.

Formulation and In Vivo Evaluation of Mucoadhesive Micro-spheres of Rebamipide, a Mucoprotective Drug for GIT Disorders

2018 ◽  
Vol 11 (3) ◽  
pp. 4089-4097
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Kanteepan P
Keyword(s):  
Drug Release ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Amino Acid Derivative ◽  
Release Mechanism ◽  
In Vivo Evaluation ◽  
In Vitro Drug Release ◽  
Percentage Yield

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. The current research study aimed to develop novel gastro-retentive mucoadhesive microspheres of rebamipide using ionotropic gelation technique. Studies of micromeritic properties confirmed that microspheres were free flowing with good packability. The in vitro drug release showed the sustained release of rebamipide up to 99.23 ± 0.13% within 12 h whereas marketed product displayed the drug release of 95.15 ± 0.23% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer-Peppas (R2 = 0.915, 0.969), respectively. The optimized M12 formulation displayed optimum features, such as entrapment efficiency 97%, particle size 61.94 ± 0.11 µm, percentage yield 98%, swelling index 95% and mucoadhesiveness was 97%. FTIR studies revealed no major incompatibility between drug and excipients. SEM confirmed the particles were of spherical in shape. Optimized formulation (M12) were stable at 40°C ± 2°C/75% RH ± 5% RH for 6 months. In vivo studies were performed and kinetic parameters like Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, and Kel  were calculated. The marketed product Cmax (3.15 ± 0.05 ng/mL) was higher than optimized formulation (2.58 ± 0.03 ng/mL). The optimized formulation AUC0-t (15.25 ± 1.14 ng.hr/mL), AUC0-∞ (19.42 ± 1.24 ng.hr/mL) was significantly higher than that of marketed product AUC0-t (10.21 ± 1.26 ng.hr/mL) and AUC0-∞ (13.15 ± 0.05 ng.hr/mL). These results indicate an optimized formulation bioavailability of 2.5-fold greater than marketed product.  

Synthesis and characterization of Chitosan-Catechol conjugates: Development and in vitro, in silico and in vivo evaluation of mucoadhesive pellets of lafutidine

2021 ◽  
pp. 088391152199784
Author(s):  
Loveleen Kaur ◽  
Ajay Kumar Thakur ◽  
Pradeep Kumar ◽  
Inderbir Singh
Keyword(s):  
Drug Release ◽  
In Silico ◽  
Ex Vivo ◽  
Strong Interactions ◽  
Dissolution Time ◽  
Sem Images ◽  
In Vivo Evaluation ◽  
Release Studies

Present study was aimed to synthesize and characterize Chitosan-Catechol conjugates and to design and develop mucoadhesive pellets loaded with lafutidine. SEM images indicated the presence of fibrous structures responsible for enhanced mucoadhesive potential of Chitosan-Catechol conjugates. Thermodynamic stability and amorphous nature of conjugates was confirmed by DSC and XRD studies respectively. Rheological studies were used to evaluate polymer mucin interactions wherein strong interactions between Chitosan-Catechol conjugate and mucin was observed in comparison to pristine chitosan and mucin. The mucoadhesion potential of Chitosan-Catechol (Cht-C) versus Chitosan (Cht) was assessed in silico using molecular mechanics simulations and the results obtained were compared with the in vitro and ex vivo results. Cht-C/mucin demonstrated much higher energy stabilization (∆E ≈ −65 kcal/mol) as compared to Cht/mucin molecular complex. Lafutidine-loaded pellets were prepared from Chitosan (LPC) and Chitosan-Catechol conjugates (LPCC) and were evaluated for various physical properties viz. flow, circularity, roundness, friability, drug content, particle size and percent mucoadhesion. In vitro drug release studies on LPC and LPCC pellets were performed for computing t50%, t90% and mean dissolution time. The values of release exponent from Korsmeyer-Peppas model was reported to be 0.443 and 0.759 for LPC and LPCC pellets suggesting Fickian and non-Fickian mechanism representing drug release, respectively. In vivo results depicted significant controlled release and enhanced residence of the drug after being released from the chitosan-catechol coated pellets. Chitosan-Catechol conjugates were found to be a promising biooadhesive polymer for the development of various mucoadhesive formulations.

scholarly journals DESIGN AND IN VITRO/IN VIVO EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF NATEGLINIDE

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Mohini Sihare ◽  
Rajendra Chouksey
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Release Profile ◽  
Matrix Tablets ◽  
In Vivo Studies ◽  
Release Mechanism ◽  
In Vivo Evaluation

Aim: Nateglinide is a quick acting anti-diabetic medication whose potent activity lasts for a short duration. One of the dangerous side effects of nateglinide administration is rapid hypoglycemia, a condition that needs to be monitored carefully to prevent unnecessary fatalities. The aim of the study was to develop a longer lasting and slower releasing formulation of nateglinide that could be administered just once daily. Methods: Matrix tablets of nateglinide were prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC), eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release patterns were evaluated using in vitro and in vivo studies. Conclusion: Of the seventeen formulated matrix tablets tested, only one formulation labelled HA-2 that contained 15% HPMC K4M demonstrated release profile we had aimed for. Further, swelling studies and scanning electron microscopic analysis confirmed the drug release mechanism of HA-2. The optimized formulation HA-2 was found to be stable at accelerated storage conditions for 3 months with respect to drug content and physical appearance. Mathematical analysis of the release kinetics of HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the sustained drug release profile we had aimed for. Keywords: Hydroxypropylmethylcellulose, Matrix tablets, Nateglinide, Sustained release

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