scholarly journals Sustained In Vitro and In Vivo Delivery of Metformin from Plant Pollen-Derived Composite Microcapsules

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1048
Author(s):  
Noha M. Meligi ◽  
Amro K.F. Dyab ◽  
Vesselin N. Paunov
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Phoenix Dactylifera ◽  
Relative Bioavailability ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley

We developed a dual microencapsulation platform for the type 2 diabetes drug metformin (MTF), which is aimed to increase its bioavailability. We report the use of Lycopodium clavatum sporopollenin (LCS), derived from their natural spores, and raw Phoenix dactylifera L. (date palm) pollens (DPP) for MTF microencapsulation. MTF was loaded into LCS and DPP via a vacuum and a novel method of hydration-induced swelling. The loading capacity (LC) and encapsulation efficiency (EE) percentages for MTF-loaded LCS and MTF-loaded DPP microcapsules were 14.9% ± 0.7, 29.8 ± 0.8, and 15.2% ± 0.7, 30.3 ± 1.0, respectively. The release of MTF from MTF-loaded LCS microcapsules was additionally controlled by re-encapsulating the loaded microcapsules into calcium alginate (ALG) microbeads via ionotropic gelation, where the release of MTF was found to be significantly slower and pH-dependent. The pharmacokinetic parameters, obtained from the in vivo study, revealed that the relative bioavailability of the MTF-loaded LCS-ALG beads was 1.215 times higher compared to pure MTF, following oral administration of a single dose equivalent to 25 mg/kg body weight MTF to streptozotocin (STZ)-induced diabetic male Sprague-Dawley rats. Significant hypoglycemic effect was obtained for STZ-induced diabetic rats orally treated with MTF-loaded LCS-ALG beads compared to control diabetic rats. Over a period of 29 days, the STZ-induced diabetic rats treated with MTF-loaded LCS-ALG beads showed a decrease in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides, cholesterol, and low-density lipoprotein-cholesterol (LDL-C) levels, as well as an increase in glutathione peroxidase (GPx) and a recovery in the oxidative stress biomarker, lipid peroxidation (LPx). In addition, histopathological studies of liver, pancreas, kidney, and testes suggested that MTF-loaded LCS-ALG beads improved the degenerative changes in organs of diabetic rats. The LCS-ALG platform for dual encapsulation of MTF achieved sustained MTF delivery and enhancement of bioavailability, as well as the improved biochemical and histopathological characteristics in in vivo studies, opening many other intriguing applications in sustained drug delivery.

Guggulsterone, a farnesoid X receptor antagonist lowers plasma trimethylamine-N-oxide levels: An evidence from in vitro and in vivo studies

2018 ◽  
Vol 38 (3) ◽  
pp. 356-370 ◽  
Author(s):  
A Gautam ◽  
YN Paudel ◽  
SAZ Abidin ◽  
U Bhandari
Keyword(s):  
Hepatic Injury ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Farnesoid X Receptor ◽  
Lipoprotein Cholesterol ◽  
In Vivo Studies ◽  
Low Density Lipoprotein Cholesterol ◽  
Pro Inflammatory Cytokines

The current study investigated the role of guggulsterone (GS), a farnesoid X receptor antagonist, in the choline metabolism and its trimethylamine (TMA)/flavin monooxygenases/trimethylamine- N-oxide (TMAO) inhibiting potential in a series of in vitro and in vivo studies as determined by high-performance liquid chromatography (HPLC), mass spectroscopy (MS), and liquid chromatography (LC)-MS techniques. Atherosclerosis (AS) was successfully induced in a group of experimental animals fed with 2% choline diet for 6 weeks. Serum lipid profiles such as total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured. Pro-inflammatory cytokines levels, markers for a hepatic injury, and oxidative stress markers were assessed. Interestingly, GS reduced the level of TMA/TMAO in both in vitro and in vivo studies as demonstrated by the peaks obtained from HPLC, MS, and LC–MS. Furthermore, GS exhibited cardioprotective and antihyperlipidemic effects as evidenced by the attenuation of levels of several serum lipid profiles and different atherogenic risk predictor indexes. GS also prevented hepatic injury by successfully restoring the levels of hepatic injury biomarkers to normal. Similarly, GS inhibited the production of pro-inflammatory cytokines levels, as well as GS, enhanced antioxidant capacity, and reduced lipid peroxidation. Histopathological study of aortic sections demonstrated that GS maintained the normal architecture in AS-induced rats. On the basis of results obtained from current investigation, we suggest that GS might have a great therapeutic potential for the treatment of AS.

Some metabolic characteristics of low-density lipoprotein subfractions, LDL-1 and LDL-2: in vitro and in vivo studies

1988 ◽  
Vol 960 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Dorine W. Swinkels ◽  
Pierre N.M. Demacker ◽  
Heidi L.M. Hak-Lemmers ◽  
Marc J.T.M. Mol ◽  
Sing H. Yap ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Vivo Studies ◽  
Low Density ◽  
Lipoprotein Subfractions ◽  
Metabolic Characteristics

scholarly journals Synthetic nanoemulsion resembling a protein-free model of 7-ketocholesterol containing low density lipoprotein: In vitro and in vivo studies

2010 ◽  
Vol 43 (4) ◽  
pp. 439-444 ◽  
Author(s):  
Giovani M Favero ◽  
Raul C Maranhão ◽  
Durvanei A Maria ◽  
Débora Levy ◽  
Sérgio P Bydlowski
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Vivo Studies ◽  
Low Density ◽  
Free Model

scholarly journals NPC1L1 Facilitates Sphingomyelin Absorption and Regulates Diet-Induced Production of VLDL/LDL-associated S1P

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2641
Author(s):  
Yoshihide Yamanashi ◽  
Tappei Takada ◽  
Hideaki Yamamoto ◽  
Hiroshi Suzuki
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
In Vivo Studies ◽  
Lipid Mediator ◽  
Low Density ◽  
Dependent Manner ◽  
Niemann Pick

Niemann-Pick C1-Like 1 (NPC1L1) is a cholesterol importer and target of ezetimibe, a cholesterol absorption inhibitor used clinically for dyslipidemia. Recent studies demonstrated that NPC1L1 regulates the intestinal absorption of several fat-soluble nutrients, in addition to cholesterol. The study was conducted to reveal new physiological roles of NPC1L1 by identifying novel dietary substrate(s). Very low-density lipoprotein and low-density lipoprotein (VLDL/LDL) are increased in Western diet (WD)-fed mice in an NPC1L1-dependent manner, so we comprehensively analyzed the NPC1L1-dependent VLDL/LDL components. Apolipoprotein M (apoM), a binding protein of sphingosine-1-phosphate (S1P: a lipid mediator), and S1P were NPC1L1-dependently increased in VLDL/LDL by WD feeding. S1P is metabolized from sphingomyelin (SM) and SM is abundant in WD, so we focused on intestinal SM absorption. In vivo studies with Npc1l1 knockout mice and in vitro studies with NPC1L1-overexpressing cells revealed that SM is a physiological substrate of NPC1L1. These results suggest a scenario in which dietary SM is absorbed by NPC1L1 in the intestine, followed by SM conversion to S1P and, after several steps, S1P is exported into the blood as the apoM-bound form in VLDL/LDL. Our findings provide insight into the functions of NPC1L1 for a better understanding of sphingolipids and S1P homeostasis.

In vitro, in vivo studies of a new amphiphilic adsorbent for the removal of low-density lipoprotein

Biomaterials ◽  
2003 ◽  
Vol 24 (13) ◽  
pp. 2189-2194 ◽  
Author(s):  
Yan Cheng ◽  
Shenqi Wang ◽  
Yaoting Yu ◽  
Yi Yuan
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Vivo Studies ◽  
Low Density

scholarly journals Rutin and Quercetin Decrease Cholesterol in HepG2 Cells but Not Plasma Cholesterol in Hamsters by Oral Administration

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3766
Author(s):  
Ning Liang ◽  
Yuk-Man Li ◽  
Zouyan He ◽  
Wangjun Hao ◽  
Yimin Zhao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Hepg2 Cells ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Regulatory Element ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Vivo Studies

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.

Transfer of newly made triglyceride from hepatocytes to preexisting extracellular very low density lipoproteins

1987 ◽  
Vol 65 (3) ◽  
pp. 337-343
Author(s):  
Gen Yoshino ◽  
George Steiner
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Liver Cells ◽  
Low Density Lipoproteins ◽  
In Vivo Studies ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Apoprotein B

Previous in vivo studies suggested a new model to describe the metabolism of very low density lipoproteins (VLDL). It was hypothesized that some of the lipoprotein triglyceride was transferred directly from hepatocytes and intestinal mucosal cells into preexisting extracellular VLDL particles. These studies employ an in vitro system to test this hypothesis. Isolated rat liver cells containing newly made radioactive triglyceride were prepared. These cells were incubated in medium to which exogenous VLDL had or had not been added. The presence of extracellular VLDL (rat or human) stimulated the transfer of labeled triglyceride out of the liver cells. This triglyceride was recovered in the medium's VLDL (as determined by its density and its precipitability by MnCl2–heparin or by anti-apoprotein B). Although these studies focussed on VLDL, preliminary data showed that similar triglyceride transfer occurred in the presence of the other apoprotein B containing lipoprotein, low density lipoprotein (LDL). However, in the presence of equivalent amounts of LDL, this triglyceride transfer was less than that seen in the presence of exogenous VLDL. Furthermore, the increased triglyceride released in the presence of LDL occurred entirely in the d < 1.006 fraction of the medium. That released in the presence of VLDL was recovered in the d > 1.006 fraction. Hence, we conclude that the transfer of the newly made triglyceride was from the cell to the extracellular lipoprotein that had been added to the medium. The transfer of triglyceride to VLDL did not depend on the synthesis and release of new VLDL particles because it was not accompanied by a change in the production of [14C]leucine VLDL protein, it was not blocked by chloroquine, and the LDL induced triglyceride release occurred into the d > 1.006 fraction. This transfer did not depend on the previously described triglyceride-transfer factor. The present in vitro studies support the model suggested by our earlier in vivo studies. The VLDL particle does not appear to be metabolized as a complete intact unit. Rather, some of its major lipid component, triglyceride, can move directly into and out of already existing extracellular lipoproteins.

scholarly journals FORMULATION AND EVALUATION OF ALGINATE-BASED MUCOADHESIVE BUCCAL PATCH FOR DELIVERY OF ANTIMIGRAINE DRUG

2018 ◽  
Vol 11 (4) ◽  
pp. 185 ◽  
Author(s):  
Gyati Shilakari Asthana ◽  
Sumit Sharma ◽  
Abhay Asthana
Keyword(s):  
Sodium Alginate ◽  
Drug Transport ◽  
Relative Bioavailability ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Average Weight ◽  
Lauryl Sulfate ◽  
Sumatriptan Succinate

 Objective: The present work was aimed with enhancement of oral bioavailability of sumatriptan succinate by sodium alginate-based mucoadhesive buccal patches.Methods: These patches were prepared by solvent-casting method using different concentrations of sodium alginate along with HPMC 5cps and maltodextrin as a film-forming polymer. Propylene glycol, sodium lauryl sulfate, and mannitol were used as plasticizer, penetration enhancer, and filler, respectively. Prepared patches were evaluated with respect to various in vitro parameters and in vivo studies were conducted on white strain New Zealand rabbits of either sex with average weight 2–3 kg.Results: All the formulations were transparent and homogeneous. F7 formulation containing Na alginate (250 mg), maltodextrin (250 mg), and HPMC 5cps (250 mg) displayed maximum folding endurance, mucoadhesive force, in vitro drug transport, and drug release and found to be stable up to 2 months in storage conditions. The pharmacokinetic parameters such as Cmax, tmax, and AUC were calculated from the data collected after in vivo studies. Sumatriptan succinate containing buccal patch displayed almost 1.73 folds and 2 folds higher Cmax and AUC, respectively, than plain drug solution. 1.93% of relative bioavailability was reported with the formulation.Conclusion: The outcome of the present work reveals that sumatriptan succinate-based mucoadhesive buccal formulation can improve overall performance of drug molecule in vitro and in vivo.

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