Fabrication and Evaluation of Quercetin Nanoemulsion: A Delivery System with Improved Bioavailability and Therapeutic Efficacy in Diabetes Mellitus

The current study was intended to fabricate and evaluate ultrasonically assisted quercetin nanoemulsion (Que-NE) for improved bioavailability and therapeutic effectiveness against diabetes mellitus in rats. Ethyl oleate, Tween 20, and Labrasol were chosen as oil, surfactant, and cosurfactant, respectively. Box–Behnken design (BBD) was employed to study the influence of process variables such as % surfactant and cosurfactant mixture (Smix) (5 to 7%), % amplitude (20–30%) and sonication time (2.5–7.5 min) on droplet size, polydispersibility index (PDI), and % entrapment efficiency (%EE) were studied. The optimization predicted that 9% Smix at 25% amplitude for 2.5 min would produce Que-NE with a droplet size of 125.51 nm, 0.215 PDI, and 87.04% EE. Moreover, the optimized Que-NE exhibited appreciable droplet size and PDI when stored at 5, 30, and 40 °C for 45 days. Also, the morphological characterization by transmission electron microscope (TEM) indicated the spherical shape of the optimized nanoemulsion. Furthermore, the Que-NE compared to pure quercetin exhibited superior release and enhanced oral bioavailability. The streptozocin-induced antidiabetic study in rats revealed that the Que-NE had remarkable protective and therapeutic properties in managing body weight, blood glucose level, lipid profile, and tissue injury markers, alongside the structure of pancreatic β-cells and hepatocytes being protected. Thus, the developed Que-NE could be of potential use as a substitute strategy for diabetes.

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Preparation, characterization and scale-up of sesamol loaded solid lipid nanoparticles

Nanotechnology Development ◽

10.4081/nd.2012.e8 ◽

2012 ◽

Vol 2 (1) ◽

pp. 8 ◽

Cited By ~ 5

Author(s):

Vandita Kakkar ◽

Indu Pal Kaur

Keyword(s):

Solid Lipid Nanoparticles ◽

Scale Up ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Solid Lipid ◽

Transmission Electron ◽

The Brain

Sesamol loaded solid lipid nanoparticles (SSLNs) were prepared with the aim of minimizing its distribution to tissues and achieving its targeting to the brain. Three scale-up batches (100x1 L) of S-SLNs were prepared using a microemulsification technique and all parameters were statistically compared with the small batch (1x;10 mL). S-SLNs with a particle size of less than 106 nm with a spherical shape (transmission electron microscopy) were successfully prepared with a total drug content and entrapment efficiency of 94.26±2.71% and 72.57±5.20%, respectively. Differential scanning calorimetry and infrared spectroscopy confirmed the formation of lipidic nanoparticles while powder X-ray diffraction revealed their amorphous profile. S-SLNs were found to be stable for three months at 5±3°C in accordance with International Conference on Harmonisation guidelines. The SLN preparation process was successfully scaled-up to a 100x batch on a laboratory scale. The procedure was easy to perform and allowed reproducible SLN dispersions to be obtained.

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Pea Protein for Hempseed Oil Nanoemulsion Stabilization

Molecules ◽

10.3390/molecules24234288 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4288 ◽

Cited By ~ 11

Author(s):

Maciej Jarzębski ◽

Farahnaz Fathordoobady ◽

Yigong Guo ◽

Minghuan Xu ◽

Anika Singh ◽

...

Keyword(s):

Droplet Size ◽

Entrapment Efficiency ◽

Box Behnken Design ◽

Pea Protein ◽

Challenge Tests ◽

Oil Emulsions ◽

The Stability ◽

Potential Food ◽

Potential Use

In this paper, we present the possibility of using pea protein isolates as a stabilizer for hempseed oil (HSO)-based water/oil emulsions in conjunction with lecithin as a co-surfactant. A Box-Behnken design was employed to build polynomial models for optimization of the ultrasonication process to prepare the emulsions. The stability of the system was verified by droplet size measurements using dynamic light scattering (DLS) as well as centrifugation and thermal challenge tests. The z-ave droplet diameters of optimized emulsion were 209 and 207 nm after preparation and 1 week storage, respectively. The concentration of free Linoleic acid (C18:2; n-6) was used for calculation of entrapment efficiency in prepared nanoemulsions. At optimum conditions of the process, up to 98.63% ± 1.95 of entrapment was achieved. FTIR analysis and rheological tests were also performed to evaluate the quality of oil and emulsion, and to verify the close-to-water like behavior of the prepared samples compared to the viscous nature of the original oil. Obtained results confirmed the high impact of lecithin and pea protein concentrations on the emulsion droplet size and homogeneity confirmed by microscopic imaging. The presented results are the first steps towards using hempseed oil-based emulsions as a potential food additive carrier, such as flavor. Furthermore, the good stability of the prepared nanoemulsion gives opportunities for potential use in biomedical and cosmetic applications.

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DESIGN AND EVALUATION OF SELF-NANO EMULSIFYING DRUG DELIVERY SYSTEMS OF ALVERINE FOR ENHANCEMENT OF SOLUBILITY

International Research Journal of Pharmacy ◽

10.7897/2230-8407.1207153 ◽

2021 ◽

Vol 12 (7) ◽

pp. 25-31

Author(s):

Pooja . ◽

Pankaj Kumar Sharma ◽

Viswanath Agrahari

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Drug Release ◽

Ethyl Oleate ◽

Spherical Shape ◽

Tween 80 ◽

In Vitro Dissolution ◽

Transmission Electron ◽

The Stability

Background: The aim of this study is to develop a liquid self-nano emulsifying drug delivery system for alverine (liquid-SNEDDS).Excipients in the alverine SNEDDS include Ethyl oleate as the oil phase, Tween 80 as a surfactant, and PEG600, Propylene glycol as a cosurfactant.The prepared eleven formulations of alverine SNEDDS were performed for emulsification time, percentage transmittance, particle size, drug release, in vitro dissolution and stability studies.The optimised alverine liquid SNEDDS formulation (D1) was studied for drug-excipient compatibility using infrared spectroscopy, as well as particle size, zeta potential, transmission electron microscopy, and stability. Alverine SNEDDS have a spherical shape with uniform particle distribution, according to their morphology. D1's optimised formulation's drug release percentage (96.6). The stability data revealed no discernible changes in drug content, emulsifying properties, drug release, or appearance. As a result, a potential SNEDDS formulation of alverine with improved solubility, dissolution rate, and bioavailability was developed.

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Tinidazole Delivery Improved by Nanosized Minicells Originated fromLeuconostoc mesenteroides

Journal of Nanomaterials ◽

10.1155/2019/7684795 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Luan Vu Kinh ◽

Dung Nguyen Anh ◽

Santa Romero Jovel ◽

Tu Nguyen Hoang Khue

Keyword(s):

Drug Delivery ◽

Electron Microscope ◽

High Performance ◽

Leuconostoc Mesenteroides ◽

Spherical Shape ◽

Food Effects ◽

Box Behnken Design ◽

Chromatography Analysis ◽

Intestinal Membrane ◽

Transmission Electron

A nanoparticle originating from natural products used as a drug delivery is considered as one of the indispensable issues in the pharmaceutical field. Increasing the bioavailability of a drug and prolonging the effect of the drug are important. Tinidazole is an antifungal agent that has absorption interfered by food. This study reported the ability ofLeuconostoc mesenteroidesVTCC B-871 in producing nanosized minicells used as drug delivery for tinidazole to improve the passage to the eaten mouse intestinal membrane. By using a scanning electron microscope and a transmission electron microscope, the morphology of the minicell loading drug was observed. The spherical shape and size (400 nm) of minicells did not change over time when kept in buffered saline gelatin and packaged with tinidazole. Based on Box-Behnken design, the optimal conditions were selected for actual encapsulation. Minicells could encapsulate tinidazole approximately to 90% which was determined by high-performance liquid chromatography analysis. The maximal concentration of tinidazole released from minicells was 70% at pH 3.4 and 55% at pH 7.2, respectively. The absorption ability of tinidazole packaging minicells was quantified in mice. Tinidazole loading minicells could be absorbed faster than tinidazole alone in fed mice via oral administration. The study assessed that the absorption of water-insoluble tinidazole could be improved byLeuconostocminicells without inhibition by food effects.

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Physicochemical Properties and Cellular Uptake of Astaxanthin-Loaded Emulsions

Molecules ◽

10.3390/molecules24040727 ◽

2019 ◽

Vol 24 (4) ◽

pp. 727 ◽

Cited By ~ 5

Author(s):

Xue Shen ◽

Tianqi Fang ◽

Jian Zheng ◽

Mingruo Guo

Keyword(s):

Whey Protein ◽

Droplet Size ◽

Cellular Uptake ◽

Water Solubility ◽

Entrapment Efficiency ◽

Protein Isolate ◽

Tween 20 ◽

Natural Pigment ◽

Physicochemical Stability ◽

Potential Benefits

Astaxanthin, a natural pigment carotenoid, is well known for its potential benefits to human health. However, its applications in the food industry are limited, due to its poor water-solubility and chemical instability. Six different emulsifiers were used to prepare astaxanthin-loaded emulsions, including whey protein isolate (WPI), polymerized whey protein (PWP), WPI-lecithin, PWP-lecithin, lecithin, and Tween20. The droplet size, zeta potential, storage stability, cytotoxicity, and astaxanthin uptake by Caco-2 cells were all investigated. The results showed that the droplet size of the emulsions ranged from 194 to 287 nm, depending on the type of emulsifier used. The entrapment efficiency of astaxanthin was as high as 90%. The astaxanthin-loaded emulsions showed good physicochemical stability during storage at 4 °C. The emulsifier type had a significant impact on the degradation rate of astaxanthin (p < 0.05). Cellular uptake of astaxanthin encapsulated into the emulsions was significantly higher than free astaxanthin (p < 0.05). Emulsion stabilized with WPI had the highest cellular uptake of astaxanthin (10.0 ± 0.2%), followed, in order, by that with PWP (8.49 ± 0.1%), WPI-lecithin (5.97 ± 0.1%), PWP-lecithin (5.05 ± 0.1%), lecithin (3.37 ± 0.2%), and Tween 20 (2.1 ± 0.1%). Results indicate that the whey protein-based emulsion has a high potential for improving the cellular uptake of astaxanthin.

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FORMULATION AND OPTIMIZATION OF ITRACONAZOLE PRONIOSOMES USING BOX BEHNKEN DESIGN

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i2.23382 ◽

2018 ◽

Vol 10 (2) ◽

pp. 41

Author(s):

Ahmed M. Samy ◽

Afaf A. Ramadan ◽

Amal S.m. Abu El-enin ◽

Yasmin I. M. Mortagi

Keyword(s):

Zeta Potential ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Slow Phase ◽

Optimum Level ◽

Box Behnken Design ◽

Vesicle Size ◽

Transmission Electron ◽

Span 60

Objective: The aim of the present study was to obtain an optimized formula of itraconazole (ITC) proniosomes using Box Behnken design.Methods: Itraconazole proniosomes were prepared using span 60 and/or brij 35 as surfactants, cholesterol and lecithin as a penetration enhancer by slurry method. Various trials have been carried out for investigation of proniosomes. Parameters such as entrapment efficiency (EE%), in vitro drug release, zeta potential, vesicle size and Transmission Electron Microscope were assessed for evaluation of proniosomes.Results: Entrapment efficiency (EE%) was found to be between 78.56% and 95.46%. The release profile of itraconazole proniosomes occurred in two distinct phases, an initial phase for about 8 h, followed by a slow phase for 16 h. The release pattern shown by these formulations was Higuchi diffusion controlled mechanism. The zeta potential values for all itraconazole proniosomes were in the range of-21.71 to-34.53 mV which confirms their stability. All itraconazoleproniosomes formula was found to be nano-sized and were appeared to be spherical in shape with sharp boundaries. One way analysis of variance (ANOVA) study showed that HLB (X1) had the main effects on most responses (Y).Conclusion: Box behnken design facilitates optimization of the formulation ingredients on entrapment efficiency, in vitro release of itraconazole proniosomes, zeta potential and vesicle size. Finally, an optimum level of factors was provided by the optimization process.

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Nanosuspension as an Efficient Carrier for Improved Ocular Permeation of Voriconazole

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021999200820154918 ◽

2020 ◽

Vol 21 ◽

Author(s):

Tang Qin ◽

Zhu Dai ◽

Xiaodi Xu ◽

Zilin Zhang ◽

Xiangyu You ◽

...

Keyword(s):

Physical Stability ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Antifungal Drugs ◽

In Vivo Experiments ◽

Transmission Electron ◽

Solvent Evaporation Process ◽

High Entrapment Efficiency

Background: The present limitations related to the ocular administration of antifungal drugs for the treatment of fungal keratitis include poor ocular bioavailability, limited retention time, and low ocular tissues penetration. Methods: This study aimed to prepare a novel ophthalmic voriconazole-loaded nanosuspension based on Eudragit RS 100. Pharmasolve® was explored as a corneal permeation enhancer in voriconazole ophthalmic formulation using in vitro and in vivo experiments. Briefly, 1% voriconazole-loaded nanosuspension was prepared using the quasi-emulsion solvent evaporation process. Results: Characterizations of the voriconazole-loaded nanosuspension by Zetasizer Nano ZS and transmission electron microscope (TEM) showed a uniform spherical shape without any agglomeration. The well-discreted nanoparticle with size of 138 ± 1.3 nm was achieved with high entrapment efficiency (98.6 ± 2.5 %) and a positive zeta potential in the range of 22.5 - 31.2 mV, indicating excellent physical stability. Discussion: Voriconazole-loaded nanosuspension containing the penetration enhancer displayed good permeability both in vitro and in vivocompared with the commercial voriconazole injection. The voriconazole-loaded nanosuspension exhibited good antifungal activity, significantly inhibiting the growth of Candida albicans at a lower concentrations of voriconazole (2.5 μg/mL, p < 0.05). Conclusion: In conclusion, the voriconazole-loaded nanosuspension containing Pharmasolve® can be used as an effective ophthalmic formu-lation for the topical ocular delivery of voriconazole.

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FORMULATION AND EVALUATION OF PRONIOSOMAL GEL-BASED TRANSDERMAL DELIVERY OF ATORVASTATIN CALCIUM BY BOX–BEHNKEN DESIGN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i4.26707 ◽

2019 ◽

pp. 335-343 ◽

Cited By ~ 2

Author(s):

SOUJANYA C ◽

RAVI PRAKASH P

Keyword(s):

Particle Size ◽

Drug Release ◽

Release Kinetics ◽

Skin Permeation ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Transmission Electron Microscopy Analysis ◽

Box Behnken Design ◽

Atorvastatin Calcium ◽

Span 60

Objective: The aim of this study was to investigate the combined influence of three independent variables in the preparation of atorvastatin proniosomes by coacervation-phase separation method. Methods: On the basis of the preliminary trials, a 3-factor, 3-level Box–Behnken design was employed to study the effect of cholesterol, soya lecithin, and Span 60 independent variable on dependent variables (particle size and % entrapment efficiency). Transmission electron microscopy analysis of optimized formulation has demonstrated the presence of individual proniosomes in spherical shape. Results: Atorvastatin optimized proniosomal formulation F2 shown better particle size and % entrapment efficiency, and also, the drug release was 99.72% within 24 h in slow and controlled manner when compared with control. Kinetic analysis of drug release profiles showed that the drug release was followed by zero-order manner with Korsmeyer–Peppas model, which implies super case II release kinetics. The particle size and zeta potential of the optimized atorvastatin proniosomal gel were found to be 65.72 and −10.5, respectively. The optimized batch of proniosomes was used for the preparation of atorvastatin-based proniosomal hydrogel by incorporating hydrated proniosomes to carbopol matrix to enhance the stability and viscosity of the system. Conclusion: The enhanced skin permeation, for a prolonged period of time, may lead to improved efficacy and better patient compliance. This study suggests that proniosomal gel-containing atorvastatin could perform therapeutically better effects than the conventional formulations.

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Microneedle-Assisted Percutaneous Delivery of Paeoniflorin-Loaded Ethosomes

Molecules ◽

10.3390/molecules23123371 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3371 ◽

Cited By ~ 7

Author(s):

Yahua Cui ◽

Yujia Mo ◽

Qi Zhang ◽

Wanwan Tian ◽

Yutao Xue ◽

...

Keyword(s):

Spherical Shape ◽

Entrapment Efficiency ◽

Topical Administration ◽

Water Soluble ◽

Orthogonal Experimental Design ◽

Therapeutic Effects ◽

Transdermal Drug Delivery System ◽

Water Soluble Drug ◽

Transmission Electron ◽

Main Component

Paeoniflorin, the main component of total glucosides of paeony (TGP), shows good therapeutic effects in arthritis, but has low bioavailability when administered orally. Avoiding such a deficiency for topical administration would expand its clinical application. This study aimed to avoid these limitations by using nanotechnology (ethosomes) and a physical approach (microneedles). Paeoniflorin-loaded ethosomal formulation (TGP-E) was optimized and evaluated in terms of entrapment efficiency (EE), particle size (PS), zeta potential (ZP), polydispersity index (PDI) and morphology. TGP-E was prepared by the hot injection method and optimized by single-factor tests and an orthogonal experimental design. The optimized paeoniflorin-loaded ethosomes had EE of 27.82 ± 1.56%, PS of 137.9 ± 7.57 nm with PDI of 0.120 ± 0.005, ZP of −0.74 ± 0.43 mV. Ethosomes showed a nearly spherical shape under the transmission electron microscope (TEM). The optimal microneedle-assisted (MN-assisted) conditions were obtained at a microneedle length of 500 μm, a pressure of 3 N and an action time of 3 min. The cumulative penetration amounts (Qn) of TGP solution transdermal (ST) and MN-assisted TGP solution transdermal (MST) were 24.42 ± 8.35 μg/cm2 and 548.11 ± 10.49 μg/cm2, respectively. Qn of TGP-E transdermal (PT) and MN-assisted TGP-E transdermal (MPT) were 54.97 ± 4.72 μg/cm2 and 307.17 ± 26.36 μg/cm2, respectively. These findings indicate that use of ethosomes and microneedles can both enhance the penetration ofpaeoniflorin, but for the water-soluble drug, there is no obvious synergism between nanotechnology and microneedles for enhancing penetration in a transdermal drug delivery system.

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Development and Optimization of Lovastatin-loaded Trans-dermal Proniosomal Gel using Box-Behnken Design

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.4.7 ◽

2018 ◽

Vol 11 (4) ◽

pp. 4196-4207

Author(s):

Soujanya C ◽

Ravi Prakash P

Keyword(s):

Particle Size ◽

Drug Release ◽

Skin Permeation ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Tween 80 ◽

Transdermal Drug Delivery System ◽

Tem Analysis ◽

Box Behnken Design ◽

The Stability

In this study, a proniosome-based transdermal drug delivery system of lovastatin was developed by coacervation phase separation method. On the basis of the pilot trials, a 3-factor, 3-level Box–Behnken design was employed to characterize the effect of Cholesterol, soya lecithin and Tween 80 on dependent variables (particle size, entrapment efficiency, and drug release). TEM analysis of optimized formulation has demonstrated the presence of individual Proniosomes in spherical shape. Lovastatin optimized proniosomal formulation F1 shown better particle size and percentage entrapment efficiency and drug release of 99.49% within 24h in slow and controlled manner when compared with control. Kinetic analysis of drug release profiles showed that the systems predominantly released Lovastatin in a zero-order manner with a strong correlation coefficient (R2= 0.9990). The particle size and Zeta potential of the optimized lovastatin proniosomal gel was found to be 138.82 nm and -11.4 mV respectively. Optimized batch of Proniosomes was used for the preparation of Lovastatin - based proniosomal hydrogel by incorporating hydrated Proniosomes to Carbopol matrix to enhance the stability and viscosity of the system. The enhanced skin permeation for prolonged time may lead to improved efficacy and better patient compliance.

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