scholarly journals Development of Natural Polysaccharide–Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment

Polymers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 3833
Author(s):  
Kanchan Kohli ◽  
Ali Mujtaba ◽  
Rozina Malik ◽  
Saima Amin ◽  
Md Sarfaraz Alam ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Statistical Design ◽  
Entrapment Efficiency ◽  
Intestinal Lumen ◽  
Pharmacokinetic Analysis ◽  
Scanning Calorimetry ◽  
Nanoparticle System

The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the P-gp expressed in the intestinal lumen. Therefore, we aimed to design and fabricate a nanoparticulate system for delivery of BBR employing naturally derived biodegradable and biocompatible polymers, mainly chitosan and alginate, to enhance the oral bioavailability of BBR. A chitosan-alginate nanoparticle system loaded with BBR (BNPs) was formulated by ionic gelation method and was optimized by employing a three-factor, three-level Box-Behnken statistical design. BNPs were characterized for various physicochemical properties, ex vivo, and in vivo evaluations. The optimized BNPs were found to be 202.2 ± 4.9 nm in size, with 0.236 ± 0.02 of polydispersity index, zeta potential -14.8 ± 1.1 mV, and entrapment efficiency of 85.69 ± 2.6%. BNPs showed amorphous nature with no prominent peak in differential scanning calorimetry (DSC) investigation. Similarly, fourier-transform infrared spectroscopy (FTIR) studies did not reveal any interaction between BBR and excipients used. The drug release followed Higuchi kinetics, since these plots demonstrated the highest linearity (R2 = 0.9636), and the mechanism of release was determined to be anomalous or non-Fickian in nature. An ex-vivo gut permeation study showed that BNPs were better internalized into the cells and more highly permeated through the intestine. Furthermore, in vivo pharmacokinetic analysis in female Wistar rats showed a 4.10−fold increase in the oral bioavailability of BBR from BNPs as compared to BBR suspension. With these findings, we have gained new insight into the effective delivery of poorly soluble and permeable drugs via a chitosan-alginate nanoparticle system to improve the therapeutic performance of an oral nanomedicine.

scholarly journals Self-Assembled Casein Nanoparticles Loading Triptolide for the Enhancement of Oral Bioavailability

2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2094835
Author(s):  
Chengxia Liu ◽  
Ting-ting Jiang ◽  
Zhi-xiang Yuan ◽  
Yu Lu
Keyword(s):  
Self Assembly ◽  
Oral Bioavailability ◽  
In Vitro Release ◽  
Area Under The Curve ◽  
Entrapment Efficiency ◽  
Infrared Spectrometry ◽  
Scanning Calorimetry ◽  
Insoluble Drugs

Triptolide (TP), a broad-spectrum antitumor drug, has very poor solubility and oral bioavailability, which limits its clinical use. Compared with conventional formulations of TP, a casein (Cas)-based drug delivery system has been reported to have significant advantages for the improvement of solubility and bioavailability of insoluble drugs. In this paper, we report the successful preparation of TP-loaded Cas nanoparticles (TP-Cas) using the self-assembly characteristics of Cas in water and the optimization of the formulation by evaluation of entrapment efficiency (EE) and loading efficiency (LE). Dynamic light scattering, transmission electron microscopy, Fourier-transform infrared spectrometry, X-ray diffractometry (XRD), and differential scanning calorimetry (DSC) was adopted to characterize the TP-Cas. Results showed that the obtained TP-Cas were approximately spherical with a particle size of 128.7 ± 11.5 nm, EE of 72.7 ± 4.7 %, and LE of 8.0% ± 0.5%. Furthermore, in vitro release behavior of TP-Cas in PBS (pH = 7.4) was also evaluated, showing a sustained-release profile. Additionally, an in vivo study in rats displayed that the mean plasma concentration of TP after oral administration of TP-Cas was significantly higher than that treated with TP oral suspension. The C max value for TP-Cas (8.0 ± 4.4 μg/mL) was significantly increased compared with the free TP (0.9 ± 0.3 μg/mL). Accordingly, the area under the curve (AUC0-8) of TP-Cas was 2.8 ± 0.8 mg/L·h, 4.3-fold higher than that of TP suspension (0.6 ± 0.1 mg/L·h). Therefore, it can be concluded that TP-Cas enhanced the absorption and improved oral bioavailability of TP. Taking the good oral safety of Cas into consideration, TP-Cas should be a more promising preparation of TP for clinical application.

scholarly journals Preparation and Characterization of Nano Structured Lipid Carriers for Ocular Bacterial Infection

2021 ◽  
pp. 8-23
Author(s):  
Shubhangi Aher ◽  
Ravindra Pal Singh ◽  
Manish Kumar
Keyword(s):  
Ex Vivo ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Tolerance Test ◽  
Stability Study ◽  
Scanning Calorimetry ◽  
Bacterial Conjunctivitis ◽  
Pure Drug

The problem of bacterial conjunctivitis has dramatically increased in recent years due increased pollution and modern lifestyle. The present study was focused to fabricate Sparfloxacin loaded nanostructured lipid carriers (Spar-NLCs) for ophthalmic application to improve ocular penetration of drug and give sustained release of drug to reduce dosing frequency and toxic effect of drug associated with ocular membrane. A regular two-level factorial design was used to optimize the formulation parameters that are significantly affecting the formulation attributes. Spar-NLCs with particle size 171.1 ± 11 nm, zeta potential -49 ± 6.47 mV, entrapment efficiency 89.5 ± 5% and spherical in shape was obtained. Besides this, FTIR spectroscopy, differential scanning calorimetry, and transmission electron microscopy results suggest that the drug is successfully incorporated in NLC and has excellent compatibility with the excipients. In vitro release study follows Korsmeyer peppas model and suggests that 81.35 ± 6.2% release of drug from Spar-NLCs in 12 hours. The result of ex-vivo permeation study demonstrated 349.75 ± 7.3 µg/cm2 of permeation of drug, 44.482 µg cm-2 hr -1 of flux, and 0.1482 cm hr-1 of permeability coefficient which is 1.7 folds higher than pure drug suspension. The antimicrobial activity of Spar-NLCs was better than the pure drug suspension and equivalent to the marketed formulation. Spar-NLC formulation did not showed any ocular damage, swelling, and redness in in -vivo Draize test. The ocular tolerance test (HET-CAM test) also suggests that the Spar-NLC formulation and its excipients were nonirritant to the ocular tissues. The formulation was found to be stable over the three month of stability study. Therefore, this work strongly suggest that Spar-NLCs has higher penetration and extended release of drug which can be effectively used in prevention of bacterial conjunctivitis.

Preparation, Characterization and in vivo Evaluation of Felodipine Solid-Lipid Nanoparticles for Improved Oral Bioavailability

2015 ◽  
Vol 8 (4) ◽  
pp. 2995-3002
Author(s):  
Kishan V ◽  
Usha Kiranmai Gondrala ◽  
Narendar Dudhipala
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Oral Bioavailability ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Lipid Nanoparticles ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation ◽  
Solid Lipid

Felodipine is an antihypertensive drug with poor oral bioavailability due to the first pass metabolism. For improving the oral bioavailability, felodipine loaded solid lipid nanoparticles (SLNs) were developed using trimyristin, tripalmitin and glyceryl monostearate. Poloxamer 188 was used as surfactant. Lipid excipient compatibilities were confirmed by differential scanning calorimetry. SLN dispersions were prepared by hot homogenization of molten lipids and aqueous phase followed by ultrasonication at a temperature, above the melting point. SLNs were characterized for particle size, zeta potential, drug content, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in 0.1N HCl and phosphate buffer of pH 6.8 using dialysis method. Pharmacokinetics of felodipine-SLNs after oral admini-stration in male Wistar rats was studied. The bioavailability of felodipine was increased by 1.75 fold when compared to that of a felodipine suspension.  

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.

Cationic Diclofenac Lipid Nanoemulsion for Improved Oral Bioavailability: Preparation, Characterization and In Vivo Evaluation

2015 ◽  
Vol 8 (2) ◽  
pp. 2874-2880
Author(s):  
Kishan Veerabrahma ◽  
Swapna Madishetty ◽  
Muzammil Afzal Syed ◽  
Prabhakar Kandadi
Keyword(s):  
Oral Bioavailability ◽  
Physical Stability ◽  
Cationic Lipid ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
In Vivo Evaluation ◽  
Drug Content ◽  
Lipid Nanoemulsion

Cationic nanoemulsions were reported to have increased bioavailability. The aim of present study was to prepare a cationic lipid nanoemulsion of diclofenac acid (LNEs) for improved oral bioavailability to treat arthritic conditions. The LNEs of diclofenac acid were prepared by using soya bean oil, egg lecithin, cholesterol and stearylamine. Stearylamine was used as positive charge inducer. The LNEs were processed by homogenization and ultrasonication. The formulation composition was selected based on earlier reports. The LNEs were characterized for size and zeta potential. The physical stability of LNEs was studied using autoclaving, centrifugal, desorption (dilution effect) stresses and on storage. The total drug content and entrapment efficiency were determined using HPLC. During in vivo studies in Wistar rats, the pharmacokinetic parameters of LNEs were compared with a prepared diclofenac suspension in sodium CMC mucilage. The selected formulations, F1, F2 and F3, were relatively stable during centrifugal stress, dilution stress and on storage. The drug content was found to be 2.38 ± 1.70 mg/ml for F1, 2.30 ± 0.82 mg/ml for F2, and 2.45 ± 0.66 mg/ml for F3. The entrapment efficiencies were 97.83 ± 0.53%, 97.87 ± 1.22% and 98.25 ± 0.21% for F1, F2 and F3 respectively. The cumulative percentage drug release from F1, F2 and F3 showed more release in pH 6.8 phosphate buffer than in pH 1.2 HCl. During oral bioavailability studies, the LNEs showed higher serum concentrations than a suspension. The relative bioavailability of the LNE formulations F1, F2 and F3 were found to be 2.35, 2.94 and 6.28 times that of F4 suspension and were statistically significant. Of all, the cationic lipid nanoemulsion (F3) was superior in improving bioavailability, when compared with plain emulsion (F1) and cholesterol containing LNE (F2). The study helps in designing the cationic oral nanoemulsions to improve the oral bioavailability of diclofenac.

Methodological Approaches to Evaluate Fetal Drug Exposure

2019 ◽  
Vol 25 (5) ◽  
pp. 496-504 ◽  
Author(s):  
Naïm Bouazza ◽  
Frantz Foissac ◽  
Déborah Hirt ◽  
Saïk Urien ◽  
Sihem Benaboud ◽  
...  
Keyword(s):  
Cord Blood ◽  
Drug Exposure ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pbpk Models ◽  
Drug Concentrations ◽  
Fetal Drug Exposure

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies. Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure. Results: Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure and showed very encouraging results. Conclusion: PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico. However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the placental permeability and transporters is strongly needed.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

Mannosylated Solid Lipid Nanocarriers Of Chrysin To Target Gastric Cancer: Optimization and Cell line Study.

2021 ◽  
Vol 18 ◽  
Author(s):  
Sonia S. Pandey ◽  
Farhinbanu I. Shaikh ◽  
Arti R. Gupta ◽  
Rutvi J. Vaidya
Keyword(s):  
Gastric Cancer ◽  
Particle Size ◽  
Ex Vivo ◽  
Biological Effects ◽  
Entrapment Efficiency ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Solid Lipid ◽  
Lipid Nanocarriers

Background: Despite significant biological effects, the clinical use of chrysin has been restricted because of its poor oral bioavailability. Objective: The purpose of the present research was to investigate the targeting potential of Mannose decorated chrysin (5,7- dihydroxyflavone) loaded solid lipid nanocarrier (MC-SLNs) for gastric cancer. Methods: The Chrysin loaded SLNs (C-SLNs) were developed optimized, characterized and further mannosylated. The C-SLNs were developed with high shear homogenizer, optimized with 32 full factorial designs and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Scanning Electron Microscope (SEM) and evaluated for particle size/polydispersity index, zeta-potential, entrapment efficiency, % release and haemolytic toxicity. The ex-vivo cytotoxicity study was performed on gastric cancer (ACG) and normal cell lines. Results: DSC and XRD data predict the chrysin encapsulation in lipid core and FTIR results confirm the mannosylation of C-SLNs. The optimized C-SLNs exhibited a narrow size distribution with a particle size of 285.65 nm. The % Entrapment Efficiency (%EE) and % controlled release were found to be 74.43% and 64.83%. Once C-SLNs were coated with mannose, profound change was observed in dependent variable - increase in the particle size of MC-SLNs (307.1 nm) was observed with 62.87% release and 70.8% entrapment efficiency. Further, the in vitro studies depicted MC- SLNs to be least hemolytic than pure chrysin and C-SLNs. MC-SLNs were most cytotoxic and were preferably taken up ACG tumor cells as evaluated against C-SLNs. Conclusion: These data suggested that the MC-SLNs demonstrated better biocompatibility and targeting efficiency to treat the gastric cancer.

Enhanced oral bioavailability of nisoldipine-piperine-loaded poly-lactic-co-glycolic acid nanoparticles

2017 ◽  
Vol 6 (6) ◽  
pp. 517-526 ◽  
Author(s):  
Permender Rathee ◽  
Anjoo Kamboj ◽  
Shabir Sidhu
Keyword(s):  
Oral Bioavailability ◽  
Drug Loading ◽  
Average Particle Size ◽  
Entrapment Efficiency ◽  
Pharmacokinetic Interaction ◽  
Precipitation Method ◽  
Pharmacokinetic Studies ◽  
Average Particle

AbstractBackground:Piperine helps in the improvement of bioavailability through pharmacokinetic interaction by modulating metabolism when administered with other drugs. Nisoldipine is a substrate for cytochrome P4503A4 enzymes. The study was undertaken to assess the influence of piperine on the pharmacokinetics and pharmacodynamics of nisoldipine nanoparticles in rats.Methods:Optimization studies of nanoparticles were performed using Taguchi L9 orthogonal array, and the nanoparticles were formulated by the precipitation method. The influence of piperine and nanoparticles was evaluated by means of in vivo kinetic and dynamic studies by oral administration in rats.Results:The entrapment efficiency, drug loading, ζ potential, and average particle size of optimized nisoldipine-piperine nanoparticles was 89.77±1.06%, 13.6±0.56%, −26.5 mV, and 132±7.21 nm, respectively. The in vitro release in 0.1 n HCl and 6.8 pH phosphate buffer was 96.9±0.48% and 98.3±0.26%, respectively. Pharmacokinetic studies showed a 4.9-fold increase in oral bioavailability and a >28.376±1.32% reduction in systemic blood pressure by using nanoparticles as compared to control (nisoldipine suspension) in Wistar rats.Conclusion:The results revealed that piperine being an inhibitor of cytochrome P4503A4 enzymes enhanced the bioavailability of nisoldipine by 4.9-fold in nanoparticles.

scholarly journals Intestinal Permeability Assays: a Review

2021 ◽  
Vol 31 (1) ◽  
pp. 20-30
Author(s):  
A. A. Iakupova ◽  
S. R. Abdulkhakov ◽  
R. K. Zalyalov ◽  
A. G. Safin ◽  
R. A. Abdulkhakov
Keyword(s):  
Intestinal Permeability ◽  
Ex Vivo ◽  
Venous Blood ◽  
Intestinal Barrier ◽  
Intestinal Lumen ◽  
Alcoholic Fatty Liver ◽  
Key Points ◽  
Assessment Techniques ◽  
Portal Venous Blood

Aim. A literature review of intestinal permeability assessment techniques.Key points. The intestinal barrier is a functional entity separating the intestinal lumen and internal body, and intestinal permeability is a measure of the barrier functionality. The intestinal barrier integrity and permeability assays differ by the application setting (in vivo or ex vivo), subject (human or animal), marker molecules used to assess permeability (ions, various size carbohydrates, macromolecules, antigens, bacterial products and bacteria), biomaterial for the marker concentration assays (peripheral blood, portal venous blood, urine, stool). Despite a great variety of methods for assessing intestinal permeability, their clinical application requires further studies due to a lack of standardisation, the complexity of selected techniques and occasional limited reliability of results.Conclusion. Further investigation and improvement of intestinal permeability assays is required. The assay and result standardisation will facilitate practice in functional and organic intestinal diseases, as well as allergies, diabetes mellitus, non-alcoholic fatty liver disease and some other illnesses.

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