In vitro and in vivo evaluation of oxygen effects on a glucose oxidase based implantable glucose sensor

1993 ◽  
Vol 281 (3) ◽  
pp. 513-520 ◽  
Author(s):  
Yanan Zhang ◽  
George S. Wilson
2017 ◽  
Vol 19 (4) ◽  
pp. 226-236 ◽  
Author(s):  
W. Kenneth Ward ◽  
Gabriel Heinrich ◽  
Matthew Breen ◽  
Sheila Benware ◽  
Nicole Vollum ◽  
...  

1994 ◽  
Vol 17 (2) ◽  
pp. 88-94 ◽  
Author(s):  
F. Moussy ◽  
D.J. Harrison ◽  
R.V. Rajotte

We have developed an implantable glucose sensor based on a new tri-layer membrane configuration. The needle-type sensor integrates a Pt working electrode and a Ag/AgCI reference electrode. Its size is equivalent to a 25 gauge needle (0.5 mm in diamater). Poly (o-phenylenediamine) was used as an inner coating to reduce interference by small compounds present in the body fluids, and the perfluorinated ionomer, Nation as a biocompatible, protective, outer coating. Glucose oxidase trapped in an albumin/glutaraldehyde matrix was sandwiched between these coatings. In vitro tests in buffer showed the sensors had a good selectively, a sensitivity of about 25 nA/mM, and a 90% response time of 33 s. Stabilization of the current following polarization required 10 to 30 min in vitro and 30 to 40 in vivo. Although these sensors remained stable for many weeks in saline solution, their implantation in animals resulted in the degradation of the protective Nation outer coating, which in turn, led to the failure of the incorporated reference electrode. We demonstrated that if unprotected, the AgCI layer of the reference electrode rapidly dissolves in the biological environment. However, we later showed that in vivo degradation of Nation can be prevented by heat curing. When heat cured sensors were subcutaneously implanted in dogs, the sensors' signal closely followed the plasma glucose level during glucose tolerance tests. The response of the sensors implanted in dogs was retained for 10 days.


1992 ◽  
Vol 15 (1) ◽  
pp. 55-61 ◽  
Author(s):  
F.J. Schmidt ◽  
A.L. Aalders ◽  
A.J.M. Schoonen ◽  
H. Doorenbos

Calibration of glucose sensors proved difficult for electrodes with immobilized glucose-oxidase. The correlation between the sensitivity of the electrodes in vitro and in vivo appeared to be poor. We developed a new type of glucose sensor, based on a microdialysis system, in which an oxygen electrode is used as detector outside the body and the enzyme glucose-oxidase dissolved in water is used as a dynamic selector. The enzyme solution is pumped through a hollow fiber placed subcutaneously, before the fluid passes the detector. The glucose sensor was tested in the subcutaneous abdominal tissue of 12 healthy volunteers and 12 type I diabetic patients. Blood glucose was clamped at two levels to permit a two-point calibration of the sensor in vivo. These values correlated well with the in vitro calibration factors (r=0.949). In subcutaneous tissue the sensor measures 43 ± 9% of the blood glucose value, using the in vitro calibration factor. No differences were detected between healthy volunteers and diabetic patients.


Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  

Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.


Author(s):  
Y. Srinivasa Rao ◽  
K. Adinarayana Reddy

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.


Author(s):  
Bhikshapathi D. V. R. N. ◽  
Kanteepan P

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.  


2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.


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