scholarly journals Enhanced Oral Bioavailability, Anti-Tumor Activity and Hepatoprotective Effect of 6-Shogaol Loaded in a Type of Novel Micelles of Polyethylene Glycol and Linoleic Acid Conjugate

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 107 ◽  
Author(s):  
Huiyun Zhang ◽  
Qilong Wang ◽  
Congyong Sun ◽  
Yuan Zhu ◽  
Qiuxuan Yang ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Oral Bioavailability ◽  
Water Solubility ◽  
Oral Absorption ◽  
Treatment Effectiveness ◽  
Hepatoprotective Effect ◽  
Nanoprecipitation Method ◽  
Acid Conjugate

：6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol’s solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG2k-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2–fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.

Lutein encapsulated oleic - linoleic acid nanoemulsion boosts oral bioavailability of retinal protective carotenoid lutein in rat model

2021 ◽  
Author(s):  
Veeresh B Toragall ◽  
Twinkle Godhwani ◽  
V Baskaran ◽  
Naveen Jayapala
Keyword(s):  
Linoleic Acid ◽  
Oral Bioavailability ◽  
Mixed Micelles ◽  
Water Solubility ◽  
Health Benefits ◽  
Aqueous Solubility ◽  
Mean Size ◽  
The Mean

Abstract There is excessive interest in emerging colloidal delivery systems to enhance the water solubility and oral bioavailability of lutein, which is a hydrophobic carotenoid claimed to possess health benefits. The present study aimed to design lutein-enriched nanoemulsions with improved physicochemical properties and to achieve various health benefits of lutein. The prepared lutein nanoemulsion was characterized, and its bioavailability was examined in vitro (simulated gastrointestinal digestion) and in vivo. The mean size, PDI and zeta potential of the lutein nanoemulsion were 110 ± 8 nm, 0.271 and 36 ± 2 mV, respectively. Furthermore, TEM examination revealed that the particles are nanosized and spherical in shape. Notably, the aqueous solubility of the nanoemulsion was 726-fold higher than that of free lutein. The composite nanoemulsion also showed exceptionally higher (87.4%) in vitro bioaccessibility than that of nonencapsulated or free lutein (15%). The in vivo bioavailability of lutein nanoemulsion (112.6 ng/mL) was much higher than that of nonencapsulated lutein (48.6 ng/ml) and mixed micelles (68.5 ng/mL), and the tissue distribution pattern of lutein nanoemulsion showed higher lutein accumulation in the liver (2.80- and 1.70-fold) and eye (1.91- and 1.48-fold) compared to free lutein and mixed micelle-fed groups. These results suggested that oleic acid-linoleic acid composite nanoemulsions may be a promising delivery system for lutein and may help enhance the solubility, oral bioavailability and bioefficacy of lutein and could be used as an ingredient for the formulation of beverages or functional foods.

scholarly journals LC478, a Novel Di-Substituted Adamantyl Derivative, Enhances the Oral Bioavailability of Docetaxel in Rats

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 135 ◽  
Author(s):  
Seung Han ◽  
Qili Lu ◽  
Kyeong Lee ◽  
Young Choi
Keyword(s):  
Oral Bioavailability ◽  
Oral Absorption ◽  
Ussing Chamber ◽  
Absolute Bioavailability ◽  
Time Curve ◽  
Glycoprotein P ◽  
Dose Concentration ◽  
Chamber Studies

P-glycoprotein (P-gp)-mediated efflux of docetaxel in the gastrointestinal tract mainly impedes its oral chemotherapy. Recently, LC478, a novel di-substituted adamantyl derivative, was identified as a non-cytotoxic P-gp inhibitor in vitro. Here, we assessed whether LC478 enhances the oral bioavailability of docetaxel in vitro and in vivo. LC478 inhibited P-gp mediated efflux of docetaxel in Caco-2 cells. In addition, 100 mg/kg of LC478 increased intestinal absorption of docetaxel, which led to an increase in area under plasma concentration-time curve (AUC) and absolute bioavailability of docetaxel in rats. According to U.S. FDA criteria (I, an inhibitor concentration in vivo tissue)/(IC50, inhibitory constant in vitro) >10 determines P-gp inhibition between in vitro and in vivo. The values 15.6–20.5, from (LC478 concentration in intestine, 9.37–12.3 μM)/(IC50 of LC478 on P-gp inhibition in Caco-2 cell, 0.601 μM) suggested that 100 mg/kg of LC478 sufficiently inhibited P-gp to enhance oral absorption of docetaxel. Moreover, LC478 inhibited P-gp mediated efflux of docetaxel in the ussing chamber studies using rat small intestines. Our study demonstrated that the feasibility of LC478 as an ideal enhancer of docetaxel bioavailability by P-gp inhibition in dose (concentration)-dependent manners.

Lipid Nanoformulations in the Treatment of Neuropsychiatric Diseases: An Approach to Overcome the Blood Brain Barrier

2020 ◽  
Vol 21 (9) ◽  
pp. 674-684 ◽  
Author(s):  
Saleha Rehman ◽  
Bushra Nabi ◽  
Faheem Hyder Pottoo ◽  
Sanjula Baboota ◽  
Javed Ali
Keyword(s):  
Blood Brain Barrier ◽  
Water Solubility ◽  
Oral Absorption ◽  
Brain Barrier ◽  
Therapeutic Drug ◽  
Blood Brain ◽  
Neuropsychiatric Diseases ◽  
The Brain

Background: Neuropsychiatric diseases primarily characterized by dementia stand third in the global list of diseases causing disability. The poor water solubility, erratic oral absorption, low bioavailability, poor intestinal absorption, and the impeding action of the blood-brain barrier (BBB) are the major factors limiting the therapeutic feasibility of the antipsychotics. Only a small percentage of antipsychotics reaches the therapeutic target site, which warrants administration of high doses, consequently leading to unwanted side-effects. Hence the main struggle for the effective treatment of neuropsychiatric diseases occurs “at the gates” of the brain, which can be mitigated with the use of a nanotechnology-based platform. Methods: The goal of this review is to undertake a comprehensive study about the role of lipid nanoformulations in facilitating the delivery of antipsychotics across BBB along with the available in vitro and in vivo evidence. Results: Lipid nanoformulations have attained great popularity for the delivery of therapeutics into the brain. Their nanosize helps in overcoming the biological barriers, thereby providing easy BBB translocation of the drugs. Besides, they offer numerous advantages like controlled and targeted drug release, minimizing drug efflux, long storage stability, augmented bioavailability, and reduced adverse drug effects to attain an optimal therapeutic drug concentration in the brain. Moreover, employing alternative routes of administration has also shown promising results. Conclusion: Thus, it can be concluded that the lipid nanoformulations bear immense potential in overcoming the challenges associated with the treatment of neuropsychiatric disorders. However, the area warrants further clinical studies to ensure their commercialization, which could revolutionize the treatment of neuropsychiatric diseases in the coming decades.

INVESTIGATION OF SOLUBILITY ENHANCEMENT OF PRASUGREL HYDROCHLORIDE: NANOSUSPENSIONS AND CYCLODEXTRIN INCLUSION COMPLEXES

INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (02) ◽  
pp. 29-38
Author(s):  
R. K Devara ◽  
◽  
P. Reddipogu ◽  
S Kumar ◽  
B. Rambabu ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Oral Bioavailability ◽  
Oral Absorption ◽  
In Vitro Dissolution ◽  
Precipitation Method ◽  
Formulation Development ◽  
Pure Drug

The objective of this study was to investigate nanosuspensions, hydroxypropyl-β-cyclodextrin (HPβCD) complexes and SLS powders for enhancing the solubility and dissolution rate of Prasugrel HCl (PHCl) so as to reduce the fluctuations in its oral bioavailability. PHCl nanosuspensions were prepared using evaporative precipitation method. HPβCD inclusion complexes of PHCl were prepared using physical mixture, co-evaporation and kneading methods. Powders of the pure drug with different SLS amounts were prepared. The formulations were characterized using techniques such as powder x-ray diffractometry, scanning electron microscopy, in vitro dissolution and in vivo absorption in rats. To further aid in the betterment of development of nevirapine nanosuspension, in vitro in vivo correlation (IVIVC) was established using deconvolution technique. Nanosuspensions and HPβCD inclusion complexes of PHCl were successfully prepared. The dissolution rate and oral absorption of PHCl in the form of nanosuspensions was significantly higher than that of HPβCD complexes, SLS powders as well as pure drug. All the techniques investigated in this study can be used to enhance dissolution rate and oral absorption of prasugrel HCl and thus can reduce the fluctuations in its oral bioavailability. Nanosuspensions demonstrated to be better and superior technique when compared to other techniques investigated in enhancing oral bioavailability of PHCl. IVIVC that could aid in further formulation development of PHCl nanosuspension was successfully developed using a deconvolution approach.

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 Recent advances in improving oral drug bioavailability by cocrystals

Bioimpacts ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 305-320 ◽  
Author(s):  
Shahram Emami ◽  
Mohammadreza Siahi-Shadbad ◽  
Khosro Adibkia ◽  
Mohammad Barzegar-Jalali
Keyword(s):  
Membrane Permeability ◽  
Oral Bioavailability ◽  
Water Solubility ◽  
Oral Absorption ◽  
Oral Drug Delivery ◽  
Oral Drug ◽  
Drug Bioavailability ◽  
Recent Advances ◽  
Intestinal Membrane

Introduction: Oral drug delivery is the most favored route of drug administration. However, poor oral bioavailability is one of the leading reasons for insufficient clinical efficacy. Improving oral absorption of drugs with low water solubility and/or low intestinal membrane permeability is an active field of research. Cocrystallization of drugs with appropriate coformers is a promising approach for enhancing oral bioavailability. Methods: In the present review, we have focused on recent advances that have been made in improving oral absorption through cocrystallization. The covered areas include supersaturation and its importance on oral absorption of cocrystals, permeability of cocrystals through membranes, drug-coformer pharmacokinetic (PK) interactions, conducting in vivo-in vitro correlations for cocrystals. Additionally, a discussion has been made on the integration of nanocrystal technology with supramolecular design. Marketed cocrystal products and PK studies in human subjects are also reported. Results: Considering supersaturation and consequent precipitation properties is necessary when evaluating dissolution and bioavailability of cocrystals. Appropriate excipients should be included to control precipitation kinetics and to capture solubility advantage of cocrystals. Beside to solubility, cocrystals may modify membrane permeability of drugs. Therefore, cocrystals can find applications in improving oral bioavailability of poorly permeable drugs. It has been shown that cocrystals may interrupt cellular integrity of cellular monolayers which can raise toxicity concerns. Some of coformers may interact with intestinal absorption of drugs through changing intestinal blood flow, metabolism and inhibiting efflux pumps. Therefore, caution should be taken into account when conducting bioavailability studies. Nanosized cocrystals have shown a high potential towards improving absorption of poorly soluble drugs. Conclusions: Cocrystals have found their way from the proof-of-principle stage to the clinic. Up to now, at least two cocrystal products have gained approval from regulatory bodies. However, there are remaining challenges on safety, predicting in vivo behavior and revealing real potential of cocrystals in the human.

scholarly journals Evaluation of a Yeast Hydrolysate from a Novel Strain of Saccharomyces cerevisiae for Mycotoxin Mitigation using In Vitro and In Vivo Models

Toxins ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 7
Author(s):  
Paul Gerard Bruinenberg ◽  
Mathieu Castex
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasma Concentration ◽  
Oral Bioavailability ◽  
Oral Absorption ◽  
Disease Risk ◽  
In Vivo Models ◽  
Monogastric Animal ◽  
Yeast Hydrolysate

Mycotoxicoses in animals are caused by exposure to mycotoxin-contaminated feeds. Disease risk is managed using dietary adsorbing agents which reduce oral bioavailability. The objective of this work was to evaluate the efficacy of three selected yeast products as mycotoxin binders using in vitro and in vivo models. Their capacity to adsorb deoxynivalenol (DON), zearalenone (ZEA), and ochratoxin A (OTA) was evaluated using an in vitro model designed to simulate the pH conditions during gastric passage in a monogastric animal. Results showed that only one product, an enzymatic yeast hydrolysate (YHY) of a novel strain Saccharomyces cerevisiae, adsorbed about 45% of DON in solution. Next, we determined the effect of YHY on oral absorption of a DON, ZEA, and OTA mixture using a toxicokinetic model in swine. Toxicokinetic modeling of the plasma concentration-time profiles of DON, OTA, and zearalenone-glucuronide (ZEA-GlcA) showed that YHY tended to reduce the maximal plasma concentration of OTA by 17%. YHY did not reduce oral bioavailability of OTA, DON, and ZEA-GlcA. Within the context of this experiment, and despite some positive indications from both the in vitro and in vivo models employed, we conclude that the YHY prototype was not an effective agent for multiple mycotoxin adsorption.

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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