scholarly journals Nanostructured Lipid Carriers Can Enhance Oral Absorption of Khellin, a Natural Pleiotropic Molecule

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7657
Author(s):  
Giulia Vanti ◽  
Lucrezia Muti ◽  
Mario D’Ambrosio ◽  
Lucia Grifoni ◽  
Maria Camilla Bergonzi ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Oral Absorption ◽  
In Vitro Release ◽  
Microscopic Analysis ◽  
Nanostructured Lipid Carriers ◽  
Therapeutic Effects ◽  
Freeze Dried ◽  
Permeability Studies ◽  
Biopharmaceutical Properties

A novel formulation based on nanostructured lipid carriers (NLCs) was developed to increase solubility and intestinal absorption of khellin. K-NLCs were prepared with stearic acid, hempseed oil, Brij S20, and Labrafil M 1944 CS, using the emulsification-ultrasonication method. Developed nanoparticles were chemically and physically characterized by liquid chromatography, light scattering techniques, and electron microscopy. The size, about 200 nm, was optimal for oral delivery, and the polydispersity index (around 0.26), indicated high sample homogeneity. Additionally, K-NLCs showed a spherical morphology without aggregation by microscopic analysis. The encapsulation efficiency of khellin was about 55%. In vitro release studies were carried out in media with different pH to mimic physiological conditions. K-NLCs were found to be physically stable in the simulated gastric and intestinal fluids, and they preserved about 70% of khellin after 6 h incubation. K-NLCs were also successfully lyophilized testing different lyoprotectants, and obtained freeze-dried K-NLCs demonstrated good shelf life over a month. Lastly, permeability studies on Caco-2 cells were performed to predict khellin passive diffusion across the intestinal epithelium, demonstrating that nanoparticles increased khellin permeability by more than two orders of magnitude. Accordingly, developed NLCs loaded with khellin represent a versatile formulation with good biopharmaceutical properties for oral administration, possibly enhancing khellin’s bioavailability and therapeutic effects.

scholarly journals A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jong Bong Lee ◽  
Masar Radhi ◽  
Elena Cipolla ◽  
Raj D. Gandhi ◽  
Sarir Sarmad ◽  
...  
Keyword(s):  
Oral Administration ◽  
Metabolic Pathway ◽  
Oral Absorption ◽  
Therapeutic Effects ◽  
The Novel ◽  
Drug Candidates ◽  
Biopharmaceutical Properties

Abstract Although adenosine and its analogues have been assessed in the past as potential drug candidates due to the important role of adenosine in physiology, only little is known about their absorption following oral administration. In this work, we have studied the oral absorption and disposition pathways of cordycepin, an adenosine analogue. In vitro biopharmaceutical properties and in vivo oral absorption and disposition of cordycepin were assessed in rats. Despite the fact that numerous studies showed efficacy following oral dosing of cordycepin, we found that intact cordycepin was not absorbed following oral administration to rats. However, 3′-deoxyinosine, a metabolite of cordycepin previously considered to be inactive, was absorbed into the systemic blood circulation. Further investigation was performed to study the conversion of 3′-deoxyinosine to cordycepin 5′-triphosphate in vitro using macrophage-like RAW264.7 cells. It demonstrated that cordycepin 5′-triphosphate, the active metabolite of cordycepin, can be formed not only from cordycepin, but also from 3′-deoxyinosine. The novel nucleoside rescue metabolic pathway proposed in this study could be responsible for therapeutic effects of adenosine and other analogues of adenosine following oral administration. These findings may have importance in understanding the physiology and pathophysiology associated with adenosine, as well as drug discovery and development utilising adenosine analogues.

scholarly journals Investigation of the Factors Responsible for the Poor Oral Bioavailability of Acacetin in Rats: Physicochemical and Biopharmaceutical Aspects

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 175
Author(s):  
Dong-Gyun Han ◽  
Eunju Cha ◽  
Jeongmin Joo ◽  
Ji Sun Hwang ◽  
Sanghyun Kim ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Oral Absorption ◽  
Systematic Investigation ◽  
Therapeutic Effects ◽  
Poor Solubility ◽  
The Poor ◽  
Acacia Honey ◽  
Biopharmaceutical Properties

Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of orally administered acacetin are limited. Moreover, the in vitro physicochemical and biopharmaceutical properties of acacetin in the gastrointestinal (GI) tract and their pharmacokinetic impacts remain unclear. Therefore, in this study, we aimed to systematically investigate the oral absorption and disposition of acacetin using relevant rat models. Acacetin exhibited poor solubility (≤119 ng/mL) and relatively low stability (27.5–62.0% remaining after 24 h) in pH 7 phosphate buffer and simulated GI fluids. A major portion (97.1%) of the initially injected acacetin dose remained unabsorbed in the jejunal segments, and the oral bioavailability of acacetin was very low at 2.34%. The systemic metabolism of acacetin occurred ubiquitously in various tissues (particularly in the liver, where it occurred most extensively), resulting in very high total plasma clearance of 199 ± 36 mL/min/kg. Collectively, the poor oral bioavailability of acacetin could be attributed mainly to its poor solubility and low GI luminal stability.

scholarly journals Folate and Borneol Modified Bifunctional Nanoparticles for Enhanced Oral Absorption

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 146 ◽  
Author(s):  
Yifan Yang ◽  
Yunzhi Yin ◽  
Jun Zhang ◽  
Tiantian Zuo ◽  
Xiao Liang ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Oral Absorption ◽  
Oral Drug Delivery ◽  
Drug Loading ◽  
In Vitro Release ◽  
Plga Nanoparticles ◽  
Oral Drug ◽  
Average Size ◽  
Promising Perspective

Oral delivery is considered the preferred route of administration due to its convenience and favorable compliance. Here, docetaxel (DTX) loaded polylactic-co-glycolic acid (PLGA) nanoparticles, coated with polyethyleneimine–folic acid (PEI-FA) and polyethyleneimine–borneol (PEI-BO), were designed to enhance oral absorption (FA/BO-PLGA-NPs). The FA/BO-PLGA-NPs were spherical and smooth with an average size of (137.0 ± 2.1) nm. Encapsulation efficiency (EE%) and drug loading (DL%) were (80.3 ± 1.8)% and (2.3 ± 0.3)%, respectively. In vitro release studies showed that approximately 62.1% of DTX was released from FA/BO-PLGA-NPs in media at pH 7.4. The reverted gut sac method showed that the absorption of FA/BO-PLGA-NPs in the intestines was approximately 6.0 times that of DTX. Moreover, cellular uptake suggested that the obtained FA/BO-PLGA-NPs could be efficiently internalized into Caco-2 cells via FA-mediated active targeting and BO-mediated P-glycoprotein (P-gp) inhibition. Pharmacokinetics study demonstrated that after oral administration of DTX at a dose of 10 mg/kg in FA/BO-PLGA-NPs, the bioavailability of FA/BO-PLGA-NPs was enhanced by approximately 6.8-fold compared with that of DTX suspension. FA/BO-PLGA-NPs caused no obvious irritation to the intestines. Overall, the FA/BO-PLGA-NP formulation remarkably improved the oral bioavailability of DTX and exhibited a promising perspective in oral drug delivery.

scholarly journals Solid Lipid Nanoparticles for Duodenum Targeted Oral Delivery of Tilmicosin

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 731 ◽  
Author(s):  
Kaixiang Zhou ◽  
Yuanyuan Yan ◽  
Dongmei Chen ◽  
Lingli Huang ◽  
Chao Li ◽  
...  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Oral Delivery ◽  
Oral Absorption ◽  
In Vitro Release ◽  
Lipid Nanoparticles ◽  
Veterinary Antibiotics ◽  
Enteric Coating ◽  
Solid Lipid ◽  
Targeted Release

Developing a targeted oral delivery system to improve the efficacy of veterinary antibiotics and reduce their consumption and environmental risks is urgent. To achieve the duodenum-targeted release of tilmicosin, the enteric granule containing tilmicosin-loaded solid lipid nanoparticles (TIL-SLNs) was prepared based on its absorption site and transport characteristics. The in vitro release, release mechanisms, stability, palatability, and pharmacokinetics of the optimum enteric granules were studied. The intestine perfusion indicated that the main absorption site of tilmicosin was shifted to duodenum from ileum by TIL-SLNs, while, the absorption of TIL-SLNs in the duodenum was hindered by P-glycoprotein (P-gp). In contrast with TIL-SLNs, the TIL-SLNs could be more effectively delivered to the duodenum in intact form after enteric coating. Its effective permeability coefficient was enhanced when P-gp inhibitors were added. Compared to commercial premix, although the TIL-SLNs did not improve the oral absorption of tilmicosin, the time to reach peak concentration (Tmax) was obviously shortened. After the enteric coating of the granules containing SLNs and P-gp inhibitor of polysorbate-80, the oral absorption of tilmicosin was improved 2.72 fold, and the Tmax was shortened by 2 h. The combination of duodenum-targeted release and P-gp inhibitors was an effective method to improve the oral absorption of tilmicosin.

scholarly journals NANOTECHNOLOGICAL APPROACH TO ENHANCE THE STABILITY AND BIOAVAILABILITY OF THE HERBAL DRUG "MURVA"

2018 ◽  
Vol 8 (5) ◽  
pp. 251-256
Author(s):  
N ARULANANDRAJ ◽  
V Gopal ◽  
S Dhivya ◽  
G Jayabalan
Keyword(s):  
Oral Absorption ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Clinical Settings ◽  
Therapeutic Effects ◽  
The Stability ◽  
Anti Fungal ◽  
Multiple Health ◽  
Vitro Release

Murva (Maerua oblongifolia) contains numerous bioactive compounds that may provide multiple health benefits, including anti-microbial, anti-fungal, anti-pyretic and anti-diabetic. Most of the therapeutic effects of murva have been attributed due to the presence of triterpenoids and alkaloids, in their composition. Although these compounds have been shown promising therapeutic effects under in-vitro conditions, they met with limited efficacy in clinical settings due to various reasons such as poor oral absorption and bioavailability. Different techniques have been proposed to improve the stability and bioavailability of the herbal drugs. Among such strategies, nanoparticulate based drug delivery systems are novel and promising tools. In this study, chitosan nanoparticles containing Murva (CNP1-CNP3) were synthesized by ionic gelation technique, which resulting in particles size smaller than 650nm. The encapsulation efficiency of nanoformulations was over 41.5%. The nanoformulations exhibited slow and sustained in vitro release over 99% of drug from the Murva encapsulated chitosan nanoparticles after 24 hours. The synthesized nanoformulations were found to be a promising system for oral sustained administration of murva and also enhances its stability and bioavailability. Keywords: Nanoparticles, Murva, chitosan, stability, bioavailability.

Development and in vitro and in vivo evaluations of a microemulsion formulation for the oral delivery of oxaprozin

2021 ◽  
Vol 18 ◽  
Author(s):  
Fangming Yin ◽  
Shu Meng ◽  
Xin Zhao ◽  
Huining Wang ◽  
Yingkai Ning ◽  
...  
Keyword(s):  
Particle Size ◽  
Oral Delivery ◽  
Oral Absorption ◽  
In Vitro Release ◽  
Tween 20 ◽  
Peak Time ◽  
Microemulsion Formulation ◽  
Vitro Release

Background: Oxaprozin is labeled as a Class II drug in the biopharmaceutical classification system, and its poor solubility in the entire gastrointestinal tract may be the main reason for its poor oral absorption capacity. Objective: The purpose of this study was to develop an oxaprozin formulation to enhance its oral absorption. Method: Oxaprozin-loaded microemulsions were prepared using the titration method and pseudoternary phase diagram. Characterization experiments were performed on microemulsion preparations, including pH, particle size, shape, zeta potential and stability (thermodynamic, dilution, and differential scanning calorimetry). Then, the in vitro release of the microemulsion and in vivo pharmacokinetics in rats were evaluated. Results : Several microemulsion formulations were prepared. The optimal formulation was 15% oleoyl macrogolglycerides, 35% Tween 20/isopropanol (Km=2) and 50% distilled water. Its particle size met the requirements, and it had a spherical shape with a negatively charged surface. This microemulsion-loaded drug was applied to in vitro release and in vivo pharmacokinetic experiments at 7.47 mg/mL. In vitro release of the oxaprozin-loaded microemulsion best fit the first-order model, while the microemulsion preparation had a certain sustained release effect. In vivo pharmacokinetic experiments indicated that the microemulsion formulation significantly delayed the peak time of the blood concentration and simultaneously prolonged the half-life of drug elimination. Conclusions : The obtained data revealed satisfactory results for this novel microemulsion of oxaprozin, which is very meaningful for clinical trials.

scholarly journals Freeze-Dried Lopinavir-Loaded Nanostructured Lipid Carriers for Enhanced Cellular Uptake and Bioavailability: Statistical Optimization, in Vitro and in Vivo Evaluations

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 97 ◽  
Author(s):  
Arshad Khan ◽  
Jahanzeb Mudassir ◽  
Safia Akhtar ◽  
Vikneswaran Murugaiyah ◽  
Yusrida Darwis
Keyword(s):  
Cellular Uptake ◽  
Chemical Interaction ◽  
In Vitro Release ◽  
Nanostructured Lipid Carriers ◽  
Simulated Gastric Fluid ◽  
Burst Release ◽  
Simulated Intestinal Fluid ◽  
Differential Scanning Calorimetry Study ◽  
Freeze Dried

Nanostructured lipid carriers (NLCs) loaded with lopinavir (LPV) were prepared by the high-shear homogenization method. The LPV-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. In vitro release studies in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) showed a burst release. The optimized freeze-dried formulation (LPV-NLC-7-Tres) had a particle size (PS), polydispersity index (PdI), zeta potential (ZP) and % entrapment efficiency (%EE) of 286.8 ± 1.3 nm, 0.413 ± 0.017, −48.6 ± 0.89 mV and 88.31 ± 2.04%, respectively. The optimized formulation observed by transmission and scanning electron microscopes showed a spherical shape. Differential scanning calorimetry study revealed the absence of chemical interaction between the drug and lipids. In vitro cellular uptake study using Caco-2 cell line showed a higher LPV uptake from LPV-NLC-7-Tres formulation compared to the free LPV-suspension. The 6-month stability study showed a minimum rise of ~40 nm in PS, while no significant changes in PdI, ZP and drug content of the LPV-NLC-7-Tres formulation stored at 5 °C ± 3 °C. The bioavailability of LPV following oral administration of LPV-NLC-7-Tres in male Wistar rats was found 6.98-fold higher than the LPV-suspension. In conclusion, the nanostructure lipid carriers are potential carriers for improving the oral bioavailability of lopinavir.

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.

Development, in vitro and in vivo Evaluations of Solid-Lipid Microparticles based on Solidified Micellar Carrier System for Oral Delivery of Cefepime

2017 ◽  
Vol 10 (1) ◽  
pp. 3582-3593
Author(s):  
Chukwuebuka Umeyor ◽  
Uchechukwu Nnadozie ◽  
Anthony Attama
Keyword(s):  
Oral Delivery ◽  
In Vitro Release ◽  
Carrier System ◽  
Solid Lipid ◽  
Solid Lipid Microparticles ◽  
Release Study ◽  
Lipid Microparticles ◽  
Vitro Release

This study seeks to formulate and evaluate a solid lipid nanoparticle-based, solidified micellar carrier system for oral delivery of cefepime. Cefepime has enjoyed a lot of therapeutic usage in the treatment of susceptible bacterial infections; however, its use is limited due to its administration as an injection only with poor patient compliance. Since oral drug administration encourage high patient compliance with resultant effect in improved therapy, cefepime was formulated as solid lipid microparticles for oral delivery using the concept of solidified micellar carrier system. The carrier system was evaluated based on particle yield, particle size and morphology, encapsulation efficiency (EE %), and thermal analysis using differential scanning calorimeter (DSC). Preliminary microbiological studies were done using gram positive and negative bacteria. In vitro release study was performed using biorelevant media, while in vivo release study was performed in white albino rats. The yield of solid lipid microparticles (SLM) ranged from 84.2 – 98.0 %. The SLM were spherical with size ranges of 3.8 ± 1.2 to 42.0 ± 1.4 µm. The EE % calculated ranged from 83.6 – 94.8 %. Thermal analysis showed that SLM was less crystalline with high potential for drug entrapment. Microbial studies showed that cefepime retained its broad spectrum anti-bacterial activity. In vitro release showed sustained release of cefepime from SLM, and in vivo release study showed high concentration of cefepime released in the plasma of study rats. The study showed that smart engineering of solidified micellar carrier system could be used to improve oral delivery of cefepime.

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