In vivo, ex vivo and in vitro Mucoadhesive Strength Assessment of Potential Pharmaceutical Bio-resource Polymer from Diospyros melonoxylon Roxb seeds

2021 ◽  
Vol 14 (1) ◽  
pp. 5307-5314
Author(s):  
Sudarshan Singh ◽  
Tanvi R Dodiya ◽  
Rajesh Dodiya ◽  
Sangeeta Singh ◽  
Sunil B Bothara
Keyword(s):  
Moisture Absorption ◽  
Guar Gum ◽  
Ex Vivo ◽  
Strength Assessment ◽  
In Vivo Test ◽  
Detachment Time ◽  
Off Time ◽  
Seed Mucilage

In this study, an oral bio-based mucoadhesive polymer was developed from Diospyros melonoxylon Roxb (Ebenaceae) seed mucilage and evaluated for mucoadhesive strength. The mucilage showed shear stress results (0.140 ± 0.0007N), with comparable adhesiveness to HPMC E5 (0.098 ± 0.0008N). Force of adhesion required to detach the seed mucilage and HPMC E5 tablets from the mucin of intestinal tissue were 0.0509 ± 0.0007 (N) and 0.0049 ± 0.0006 (N). Seed mucilage revealed significant higher detachment time, erosion time, in vitro wash off time and ex vivo residence compared to HPMC E5 and lactose tablets (p<0.01). In vivo test indicated that seed mucilage tablets possessed good mucoadhesive strength compared to HPMC E5 and resisted disintegration for ≤ 8 h. The swelling index and wetting time showed comparable results between the mucilage and synthetic polymer tablets. Mucilage demonstrated high moisture absorption, percentage hydration, and matrix erosion of 20.0 ± 0.037, 53.66 ± 0.127, and 20.00 ± 0.077 compared to HPMC E5 10.0 ± 0.079, 36.00 ± 0.089, and 1.26 ± 0.085. The mucoadhesive properties of seeds mucilage were comparable to guar gum and HPMC E5. Thus, seed mucilage of D. melonoxylon can be exploited for usage as pharmaceutical excipient in oral bioadhesive drug delivery systems.

Bio-based Polymer Isolated from Seeds of Buchanania lanzan Spreng with Potential Use as Pharmaceutical Mucoadhesive Excipient

2020 ◽  
Vol 13 (4) ◽  
pp. 5028-5035
Author(s):  
Sudarshan Singh ◽  
Tanvi R Dodiya ◽  
Sangeeta Singh ◽  
Rajesh Dodiya ◽  
Sunil B Bothara
Keyword(s):  
Moisture Absorption ◽  
Guar Gum ◽  
Ex Vivo ◽  
In Vivo Test ◽  
Wetting Time ◽  
Detachment Time ◽  
Off Time ◽  
Seed Mucilage

This study was aimed to develop an oral bio-based mucoadhesive polymer from seeds mucilage of Buchanania lanzan spreng, belongs to family anacardiaceae. Isolated mucilage was evaluated for mucoadhesive strength and compared with existing polymer. The mucilage showed shear stress results (0.099 ± 0.0001N), with comparable adhesiveness to methocel E5 (0.098 ± 0.0008N). Force of adhesion required to detach the seed mucilage and methocel E5 tablets from the mucin of intestinal tissue were 0.0276 ± 0.0019 (N) and 0.0049 ± 0.0006 (N), respectively. Seed mucilage revealed significant (P<0.01) higher detachment time, erosion time, in-vitro wash-off time and ex-vivo residence compared to methocel E5 and lactose tablets. In vivo test indicated that seed mucilage tablets possessed good mucoadhesive strength compared to methocel E5 and resisted disintegration for ≤ 8 h. The swelling index and wetting time showed comparable results between the mucilage and synthetic polymer tablets. Mucilage demonstrated high moisture absorption, percentage hydration, and matrix erosion of 18.57 ± 0.036, 50.00 ± 0.051, and 8.30 ± 0.155 compared to methocel E5 10.0 ± 0.079, 36.00 ± 0.089, and 1.26 ± 0.085, respectively. Mucoadhesive properties of seeds mucilage were comparable to guar gum and methocel E5, thus seed mucilage of B. lanzan can be potentially exploited for usage as a bioadhesive pharmaceutical excipient.

scholarly journals In vivo mucoadhesive strength appraisal of gum Manilkara zapota

2015 ◽  
Vol 51 (3) ◽  
pp. 689-698 ◽  
Author(s):  
Singh Sudarshan ◽  
Bothara Sunil B
Keyword(s):  
Drug Delivery Systems ◽  
Guar Gum ◽  
Methyl Cellulose ◽  
Synthetic Polymers ◽  
Chemical Modifications ◽  
Experimental Conditions ◽  
Manilkara Zapota ◽  
Seed Mucilage

The mucilage (MMZ) extracted from the seeds of Manilkara zapota(Linn.) P. Royen syn. using maceration techniques was evaluated for mucoadhesive strength by various in vitro and in vivo methods. The result showed that mucoadhesive strength of seeds mucilage have comparable property toward natural and synthetic polymers such as Guar Gum and hydroxyl propyl methyl cellulose (HPMC E5LV) under the experimental conditions used in this study. Briefly, it could be concluded that the seed mucilage of Manilkara zapota can be used as a pharmaceutical excipient in oral mucoadhesive drug delivery systems. Further, it may be appropriate to study the changes in these properties after chemical modifications.

Development of Promethazine Hydrochloride Mucoadhesive Patches for Buccal Delivery: In vitro, Ex vivo and In vivo Characterization

2012 ◽  
Vol 5 (2) ◽  
pp. 1697-1705
Author(s):  
Y. Madhusudan Rao ◽  
Chopparapu K S C ◽  
P. Chinna Reddy ◽  
Narender Doodipala
Keyword(s):  
Drug Release ◽  
Moisture Absorption ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Physicochemical Interaction ◽  
Surface Ph ◽  
Drug Permeation ◽  
Promethazine Hydrochloride

Promethazine hydrochloride (PMZ HCl), an antiemetic, undergoes extensive first-pass metabolism (bioavailability 25%). The purpose of the present investigation was to develop mucoadhesive patches for transbuccal delivery of PMZ HCl using solvent casting technique with Hydroxy ethyl cellulose (Natrosol 250 E) and hydroxylpropyl methyl cellulose as mucoadhesive polymers and propylene glycol as the plasticizer and evaluate their physicochemical characteristics, in vitro drug release, moisture absorption, surface pH, mechanical properties, in vitro bioadhesion, in vivo residence time, and ex vivo drug permeation through porcine buccal membranes from optimized buccal patch and stability studies. The physicochemical interaction between PMZ HCl and polymers was investigated by Fourier Transform Infrared Spectroscopy. Ex vivo drug permeation through porcine buccal membrane was performed and 83.7% of the drug permeated in 6 hours with flux 0.19 mg h–1cm–2. The optimized formulation AA4 showed maximum drug release (98%) in 6 hours in the Higuchi model release profile. Moisture absorption, surface pH, tensile strength, elongation at break, peak detachment force and work of adhesion values of the optimized formulation were found to be 68.1%, pH 6.7, 12.3 kg/mm2, 69.2 % mm2, 7.5 N and 2.73 mJ respectively. Formulation AA4 showed 77.6% of the drug permeated through porcine buccal membrane in 6 hours and flux calculated to be 0.45 mg h–1cm–2. FTIR studies showed no evidence of interaction between the drug and polymers. In vivo mucoadhesive behaviour of the optimized formulation was studied in healthy human volunteers and subjective parameters were evaluated. The stability of the optimized formulation was studied and no significant changes were detected in drug content, in vitro release and ex vivo permeation after 6 months.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

1992 ◽  
Vol 67 (06) ◽  
pp. 660-664 ◽  
Author(s):  
Virgilio Evangelista ◽  
Paola Piccardoni ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Platelet Activation ◽  
Polymorphonuclear Leukocytes ◽  
Direct Interaction ◽  
Cathepsin G ◽  
In Vivo Test ◽  
Cell Functions ◽  
Test Models ◽  
Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

Organische Nitrate und Thrombozytenfunktion

1988 ◽  
Vol 08 (02) ◽  
pp. 90-99 ◽  
Author(s):  
H. Schröder ◽  
K. Schrör
Keyword(s):  
Endothelial Cell ◽  
Angina Pectoris ◽  
Ex Vivo

ZusammenfassungOrganische Nitrate unterschiedlicher chemischer Struktur sowie Nitroprussidnatrium und Molsidomin (bzw. ihre biologisch aktiven Metaboliten) können die (primäre) Aggregation und Sekretion von Humanthrombozyten in vitro und ex vivo hemmen. Eine solche Wirkung wird für Molsidomin (SIN-1) und Nitroprussidnatrium in vitro in Konzentrationen beobachtet, die in der gleichen Größenordnung liegen wie die vasodilatierenden Effekte der Substanzen. Dagegen sind für eine direkte Antiplättchenwirkung organischer Nitrate (Glyzeryltrinitrat, Isosorbiddinitr at, Isosorbidmononitrate, Teopranitol) in vitro Konzentrationen erforderlich, die ca. 100- bis 1000fach höher sind als die Plasmaspiegel der Substanzen nach therapeutischer Dosierung bzw. die Konzentrationen, die isolierte Gefäßstreifen relaxieren. Als gemeinsamer Wirkungsmechanismus der direkten thrombozy-tenfunktionshemmenden und gefäßerweiternden Wirkung all dieser Substanzen kann heute eine Stickoxid-(NO)-vermittelte Stimulation der cGMP-Bildung angenommen werden, das aus organischen Nitraten als »Pro-drug« entsteht. Die Freisetzung von NO, eines »endothelial cell-derived relaxing factors« (EDRF) aus Nitroprussidnatrium und SIN-1 erfolgt spontan. Dagegen erfordert die Freisetzung von NO aus organischen Nitraten einen enzymatischen Stoffwechselweg, der in isolierten Thrombozyten nicht vorhanden ist. Eine Antiplättchenwirkung organischer Nitrate in vivo bzw. ex vivo wird daher über die Stimulation eines endothelialen, thrombozyteninhibitorischen Faktors erklärt. Hierbei sind Prostazyklin sowie ein bisher unbekannter Endothel-zellfaktor neben einer synergistischen Wirkung organischer Nitrate mit endogenem Prostazyklin in Diskussion. Eine thrombozytenfunktionshemmen-de Wirkung organischer Nitrate könnte in Kombination mit ihren hämody-namischen Effekten auch für die an-tianginöse Wirkung in der Klinik bedeutsam sein, insbesondere zur Verhinderung vasospastischer Zustände bei der instabilen Angina pectoris.

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