scholarly journals Optimization and Evaluation of Piperine Loaded Herbosomes for their Antioxidant and Hepatoprotective Potential

2022 ◽  
Vol 34 (2) ◽  
pp. 383-388
Author(s):  
Gayatri Joshi ◽  
Abhishek Tiwari ◽  
Prashant Upadhyay
Keyword(s):  
Entrapment Efficiency ◽  
Aqueous Solubility ◽  
Hepatoprotective Activity ◽  
The Body ◽  
Oral Dosage ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Homogeneous Population ◽  
Ic50 Value

Piperine is classified as a class II drug in the biopharmaceutical classification system due to its low aqueous solubility. As a result, piperine herbosomes were created to improve the dissolution rate and in vivo liver protecting activity of piperine and physico-chemical characteristics were used to confirm herbosome formation. The piperine-herbosome formulation revealed spherical particle size of all formulations from P1-P10 and found142.4 ± 0.98 nm for best piperine-herbosome formulation (P2) and a PDI value of 0.237, indicating a homogeneous population of piperine loaded vesicles. In vitro drug release rate and percent entrapment efficiency were determined for all formulations P1-P25 and found to be 95.306 ± 0.21 and 97.306 ± 0.65 in 12 h, respectively for best piperine-herbosome formulation (P2). It exemplifies the complex’s long-term releasing capability. This information suggests that it may have a longer retention time inside the body, extending the duration of effect. The antioxidant potential of pure piperine was determined using the DPPH scavenging method, with an IC50 value of 107.59 ± 0.11 g/mL compared to a formulation with an IC50 value of 93.926 ± 0.03 g/mL. Swiss albino mice of either sex were utilized for the evaluation of hepatoprotective activity. On the 8th day, the hepatotoxicity was caused by giving a single oral dosage of CCl4 (0.5 mL) and the parameters were evaluated on the 9th day. This formulation has the best optimized based on drug content and drug entrapment. Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin were among the biochemical markers measured. In comparison to normal control (161 ± 0.31 IU/L, 52.78 ± 0.28 IU/L, 121.12 ± 0.14 IU/L and 0.633 ± 1.44 IU/L) and P2 formulation (163.23 ± 0.49 IU/L, 66.9 ± 0.05 IU/L, 128.3 ± 1.15 IU/L and 0.645 ± 0.67 IU/L respectively).

scholarly journals Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy

Polymers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 923
Author(s):  
Shadab Md ◽  
Nabil A. Alhakamy ◽  
Hibah M. Aldawsari ◽  
Mohammad Husain ◽  
Nazia Khan ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Zeta Potential ◽  
Skin Permeation ◽  
Entrapment Efficiency ◽  
Aqueous Solubility ◽  
Skin Layer ◽  
Vesicle Size ◽  
Cytotoxicity Activities

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ±6.0 and 79.43 ± 12.43 µg/ cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.

COMPARATIVE EVALUATION OF IN VITRO ANTIOXIDANT AND IN VIVO HEPATOPROTECTIVE ACTIVITIES OF ETHANOLIC LEAF AND ROOT EXTRACTS OF CLEOME GYNANDRA

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (04) ◽  
pp. 50-56
Author(s):  
K Ravishankar ◽  
Y.V.V.M. Lakshmi Prasanna ◽  
G.V.N. Kiranmayi ◽  
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatoprotective Activity ◽  
Root Extract ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Root Extracts ◽  
Cleome Gynandra ◽  
Ic50 Values ◽  
Ethanolic Leaf Extract

In vitro antioxidant and in vivo hepatoprotective activities of Cleome gynandra ethanolic leaf and root extracts were assessed. In vitro antioxidant activity was carried by DPPH, Nitric oxide, hydroxyl radical and phosphomolybdenum assays. Hepatoprotective activity was evaluated by Carbon tetrachloride (CCl4) induced hepatotoxicity in albino rats.The animals were divided into seven groups (Four test groups - Ethanolic Leaf and Root Extracts of Cleome gynandra of 100 mg/kg and 200 mg/kg, standard silymarin (100 mg/kg), toxic control-carbon tetrachloride and vehicle). On the eight day, the blood was collected and parameters like serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), Alkaline phosphatase (ALP) and Total bilirubin (TB) were estimated. Significant antioxidant status with good IC50 values similar to standard ascorbic acid was obtained. A significant decrease in liver enzymes was observed in test groups comparable to silymarin. From the results obtained, ethanolic leaf extract has contributed better hepatoprotection compared with root extract in experimental rats.

IN VITRO ANTIOXIDANT AND IN VIVO HEPATOPROTECTIVE ACTIVITY OF ETHANOLIC EXTRACT OF ZIZIPHUS RUGOSA LAM. LEAVES

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (07) ◽  
pp. 69-75
Author(s):  
S Parashar ◽  
V. Uplanchiwar ◽  
R. K. Gautam ◽  
S. Goyal ◽  
Keyword(s):  
Free Radical ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Ethanolic Extract ◽  
Hepatoprotective Activity ◽  
Free Radical Scavenging ◽  
Scavenging Activity ◽  
Ic50 Value

Ziziphus rugosa Lam. belongs to the family Rhamnaceae and is found chiefly in deciduous and semi evergreen forest of Western Ghats. The present research was undertaken to establish in vitro antioxidant and in vivo hepatoprotective activity of ethanolic extract of Z.rugosa Lam. leaves. The powdered leaves of Z. rugosa were extracted with ethanol and preliminary phytochemical screening was performed for the presence of various phytoconstituents. DPPH assay and β-glucuronidase inhibition assay were selected for the free radical scavenging activity. For the assessment of hepatoprotective activity, alcohol and CCl4 induced hepatotoxicity model were used. The phytochemical analysis of ethanolic extract showed the presence of alkaloids, saponins and flavonoids. The extract exhibited concentration dependent radical scavenging activity with an IC50 value of 61.88 μg/ml and β –glucoronidase inhibition activity with an IC50 value of 70.61 μg/ml. It was speculated that the Z. rugosa Lam. ethanolic extract shows dosedependent hepatoprotective activity which is equivalent with the standard drug Silymarin. The inhibition of free radicals or free radical scavenging activity is significant in the protection against CCl4 and alcohol induced hepatopathy. Hence, it is likely that the antioxidant activity of ethanolic extract of Z. rugosa Lam. might contribute to the hepatoprotective action.

scholarly journals Optimisation of a Microfluidic Method for the Delivery of a Small Peptide

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1505
Author(s):  
Felicity Y. Han ◽  
Weizhi Xu ◽  
Vinod Kumar ◽  
Cedric S. Cui ◽  
Xaria Li ◽  
...  
Keyword(s):  
Half Life ◽  
Drug Loading ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
The Body ◽  
Related Factors ◽  
Elimination Half ◽  
Therapeutic Peptides

Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases.

Preparation and Evaluation of Quercetin-Loaded MPEG-PLA Nanoparticles

2018 ◽  
Vol 14 (5) ◽  
pp. 366-376 ◽  
Author(s):  
Hiraku Onishi ◽  
Masashi Nakamura ◽  
Masanaho Sasatsu
Keyword(s):  
Organic Solvent ◽  
Therapeutic Potential ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
The Body ◽  
In Vivo Studies ◽  
Water Mixture ◽  
Biodistribution Studies

Background: Quercetin (QE) is one of the flavonoids with various biological functions such as anti-oxidation, anti-inflammatory and antitumor. However, the low aqueous solubility and short half-life in the body reduce its in vivo efficacy. Therefore, the appropriate delivery techniques to solve those problems have drawn much attention. In the present study, methoxypolyethylene glycol- poly-DL-lactic acid (MPEG-PLA) nanoparticles loaded with quercetin (QE), called NP, were prepared, and their antitumor characteristics were investigated in vitro and in vivo. Method: NPs were produced by evaporating organic solvent from the organic solvent-water mixture in four formulations. The particle characteristics and in vitro release were examined for the obtained preparations (NP1 – NP4). The antitumor features were investigated in vivo with different administration schedules using mice inoculated subcutaneously with murine Sarcoma 180. In addition, the efficacy of co-administration of NP with a strong antitumor chemotherapeutic agent, irinotecan hydrochloride (CPT-11), was examined. Biodistribution studies were performed using the same animal models. Result: The NP with the higher drug content (0.58 % (w/w)) and gradual release profile, Preparation NP4, were chosen and used as NP in the in vivo studies. NP suppressed tumor growth better than QE solution in various dosing schedules (total dose = 2 mg/kg). In the combination therapy with CPT-11, NP exhibited antitumor efficacy in a nearly additive manner. No decrease in body weight observed with any administration. NP markedly enhanced the systemic distribution and tumor localization. Conclusion: These results indicated that the present NP should promote the efficacy of QE, and might have useful therapeutic potential in the treatment of solid tumors.

scholarly journals Quercetin Loaded Monolaurate Sugar Esters-Based Niosomes: Sustained Release and Mutual Antioxidant—Hepatoprotective Interplay

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 143 ◽  
Author(s):  
Enas Elmowafy ◽  
Marwa O. El-Derany ◽  
Francesca Biondo ◽  
Mattia Tiboni ◽  
Luca Casettari ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Spherical Shape ◽  
Aqueous Solubility ◽  
Biological Properties ◽  
Hepatoprotective Activity ◽  
Molar Ratio ◽  
Drug Release Profile ◽  
Sugar Esters

Flavonoids possess different interesting biological properties, including antibacterial, antiviral, anti-inflammatory and antioxidant activities. However, unfortunately, these molecules present different bottlenecks, such as low aqueous solubility, photo and oxidative degradability, high first-pass effect, poor intestinal absorption and, hence, low systemic bioavailability. A variety of delivery systems have been developed to circumvent these drawbacks, and among them, in this work niosomes have been selected to encapsulate the hepatoprotective natural flavonoid quercetin. The aim of this study was to prepare nanosized quercetin-loaded niosomes, formulated with different monolaurate sugar esters (i.e., sorbitan C12; glucose C12; trehalose C12; sucrose C12) that act as non-ionic surfactants and with cholesterol as stabilizer (1:1 and 2:1 ratio). Niosomes were characterized under the physicochemical, thermal and morphological points of view. Moreover, after the analyses of the in vitro biocompatibility and the drug-release profile, the hepatoprotective activity of the selected niosomes was evaluated in vivo, using the carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Furthermore, the levels of glutathione and glutathione peroxidase (GSH and GPX) were measured. Based on results, the best formulation selected was glucose laurate/cholesterol at molar ratio of 1:1, presenting spherical shape and a particle size (PS) of 161 ± 4.6 nm, with a drug encapsulation efficiency (EE%) as high as 83.6 ± 3.7% and sustained quercetin release. These niosomes showed higher hepatoprotective effect compared to free quercetin in vivo, measuring serum biomarker enzymes (i.e., alanine and aspartate transaminases (ALT and AST)) and serum biochemical parameters (i.e., alkaline phosphatase (ALP) and total proteins), while following the histopathological investigation. This study confirms the ability of quercetin loaded niosomes to reverse CCl4 intoxication and to carry out an antioxidant effect.

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.

Репрограммированые in vitro на М3 фенотип макрофаги останавливают рост солидной карциномы in vivo

2018 ◽  
pp. 41-46
Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Antitumor Effect ◽  
Tumor Development ◽  
Significant Inhibition ◽  
The Body ◽  
Ehrlich Carcinoma ◽  
Solid Carcinoma ◽  
Ec Cells

Цель исследования. Доказательство гипотезы, что репрограммированные in vitro на М3 фенотип макрофаги при введении в организм будут существенно ограничивать развитие солидной карциномы in vivo . Методика. Рост солидной опухоли инициировали у мышей in vivo путем подкожной инъекции клеток карциномы Эрлиха (КЭ). Инъекцию макрофагов с нативным М0 фенотипом и с репрограммированным M3 фенотипом проводили в область формирования солидной КЭ. Репрограммирование проводили с помощью низких доз сыворотки, блокаторов факторов транскрипции STAT3/6 и SMAD3 и липополисахарида. Использовали две схемы введения макрофагов: раннее и позднее. При раннем введении макрофаги вводили на 1-е, 5-е, 10-е и 15-е сут. после инъекции клеток КЭ путем обкалывания макрофагами с четырех сторон область развития опухоли. При позднем введении, макрофаги вводили на 10-е, 15-е, 20-е и 25-е сут. Через 15 и 30 сут. после введения клеток КЭ солидную опухоль иссекали и измеряли ее объем. Эффект введения макрофагов оценивали качественно по визуальной и пальпаторной характеристикам солидной опухоли и количественно по изменению ее объема по сравнению с группой без введения макрофагов (контроль). Результаты. Установлено, что M3 макрофаги при раннем введении от начала развития опухоли оказывают выраженный антиопухолевый эффект in vivo , который был существенно более выражен, чем при позднем введении макрофагов. Заключение. Установлено, что введение репрограммированных макрофагов M3 ограничивает развитие солидной карциномы в экспериментах in vivo . Противоопухолевый эффект более выражен при раннем введении М3 макрофагов. Обнаруженные в работе факты делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли, путем предварительного программирования антиопухолевого врожденного иммунного ответа «в пробирке». Aim. To verify a hypothesis that macrophages reprogrammed in vitro to the M3 phenotype and injected into the body substantially restrict the development of solid carcinoma in vivo . Methods. Growth of a solid tumor was initiated in mice in vivo with a subcutaneous injection of Ehrlich carcinoma (EC) cells. Macrophages with a native M0 phenotype or reprogrammed towards the M3 phenotype were injected into the region of developing solid EC. Reprogramming was performed using low doses of serum, STAT3/6 and SMAD3 transcription factor blockers, and lipopolysaccharide. Two schemes of macrophage administration were used: early and late. With the early administration, macrophages were injected on days 1, 5, 10, and 15 following the injection of EC cells at four sides of the tumor development area. With the late administration, macrophages were injected on days 10, 15, 20, and 25. At 15 and 30 days after the EC cell injection, the solid tumor was excised and its volume was measured. The effect of macrophage administration was assessed both qualitatively by visual and palpation characteristics of solid tumor and quantitatively by changes in the tumor volume compared with the group without the macrophage treatment. Results. M3 macrophages administered early after the onset of tumor development exerted a pronounced antitumor effect in vivo , which was significantly greater than the antitumor effect of the late administration of M3 macrophages. Conclusion. The observed significant inhibition of in vivo growth of solid carcinoma by M3 macrophages makes promising the development of a clinical version of the biotechnology for restriction of tumor growth by in vitro pre-programming of the antitumor, innate immune response.

Ruthenium Complexes for 1- and 2-Photon Photodynamic Therapy: From In Silico Prediction to In Vivo Applications

2020 ◽  
Author(s):  
Johannes Karges ◽  
Shi Kuang ◽  
Federica Maschietto ◽  
Olivier Blacque ◽  
Ilaria Ciofini ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
In Silico ◽  
Aqueous Solubility ◽  
The Body ◽  
Photon Absorption ◽  
Multicellular Tumor Spheroids ◽  
Spectral Window ◽  
Photon Excitation ◽  
Polypyridine Complexes

<div>The use of photodynamic therapy (PDT) against cancer has received increasing attention overthe recent years. However, the application of the currently approved photosensitizers (PSs) is somehow limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E’)-4,4´-bisstyryl 2,2´-bipyridine ligands showed impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While non-toxic in the dark, these compounds were found phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and be able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2 Photon excitation.</div>

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

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.

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