scholarly journals Formulation, Characterization, and Cytotoxicity Evaluation of Lactoferrin Functionalized Lipid Nanoparticles for Riluzole Delivery to the Brain

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 185
Author(s):  
Maria Inês Teixeira ◽  
Carla Martins Lopes ◽  
Hugo Gonçalves ◽  
José Catita ◽  
Ana Margarida Silva ◽  
...  
Keyword(s):  
Encapsulation Efficiency ◽  
Substantial Reduction ◽  
In Vitro Release ◽  
Spherical Shape ◽  
Melting Behavior ◽  
Protein Quantification ◽  
Polydispersity Index ◽  
Brain Targeting ◽  
The Brain

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain.

scholarly journals Tailoring Midazolam-Loaded Chitosan Nanoparticulate Formulation for Enhanced Brain Delivery via Intranasal Route

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2589
Author(s):  
Nikesh Shrestha ◽  
Saba Khan ◽  
Yub Raj Neupane ◽  
Shweta Dang ◽  
Shadab Md ◽  
...  
Keyword(s):  
Particle Size ◽  
Drug Loading ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Area Under The Curve ◽  
Brain Targeting ◽  
Brain Delivery ◽  
Nanoparticle Formulation ◽  
The Brain

In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (Cmax 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ solution (Cmax 245.44 ± 12.83 ng/mL, tmax 1 h, and AUC0-480 1208.94 ng.min/mL) and IN administration of MDZ solution (Cmax 211.67 ± 12.82, tmax 2 h, and AUC0-480 1036.78 ng.min/mL). The brain–blood ratio of MDZ-CSNPs (IN) were significantly greater at all sampling time points when compared to that of MDZ solution (IV) and MDZ (IN), which indicate that direct nose-to-brain delivery by bypassing the blood–brain barrier demonstrates superiority in brain delivery. The drug-targeting efficiency (DTE%) as well as nose-to-brain direct transport percentage (DTP%) of MDZ-CSNPs (IN) was found to be comparatively higher than that for other formulations, suggesting better brain targeting potential. Thus, the obtained results demonstrated that IN MDZ-CSNP has come up as a promising approach, which exhibits tremendous potential to mark a new landscape for the treatment of status epilepticus.

Optimization and Characterization of Aqueous Micellar Formulations for Ocular Delivery of an Antifungal Drug, Posaconazole

2020 ◽  
Vol 26 (14) ◽  
pp. 1543-1555 ◽  
Author(s):  
Meltem E. Durgun ◽  
Emine Kahraman ◽  
Sevgi Güngör ◽  
Yıldız Özsoy
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Size Distribution ◽  
Encapsulation Efficiency ◽  
Fungal Infections ◽  
In Vitro Release ◽  
Pluronic F127 ◽  
Glycol Succinate ◽  
Vitro Release

Background: Topical therapy is preferred for the management of ocular fungal infections due to its superiorities which include overcoming potential systemic side effects risk of drugs, and targeting of drugs to the site of disease. However, the optimization of effective ocular formulations has always been a major challenge due to restrictions of ocular barriers and physiological conditions. Posaconazole, an antifungal and highly lipophilic agent with broad-spectrum, has been used topically as off-label in the treatment of ocular fungal infections due to its highly lipophilic character. Micellar carriers have the potential to improve the solubility of lipophilic drugs and, overcome ocular barriers. Objective: In the current study, it was aimed optimization of posaconazole loaded micellar formulations to improve aqueous solubility of posaconazole and to characterize the formulations and to investigate the physical stability of these formulations at room temperature (25°C, 60% RH), and accelerated stability (40°C, 75% RH) conditions. Method: Micelles were prepared using a thin-film hydration method. Pre-formulation studies were firstly performed to optimize polymer/surfactant type and to determine their concentration in the formulations. Then, particle size, size distribution, and zeta potential of the micellar formulations were measured by ZetaSizer Nano-ZS. The drug encapsulation efficiency of the micelles was quantified by HPLC. The morphology of the micelles was depicted by AFM. The stability of optimized micelles was evaluated in terms of particle size, size distribution, zeta potential, drug amount and pH for 180 days. In vitro release studies were performed using Franz diffusion cells. Results: Pre-formulation studies indicated that single D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), a combination of it and Pluronic F127/Pluronic F68 are capable of formation of posaconazole loaded micelles at specific concentrations. Optimized micelles with high encapsulation efficiency were less than 20 nm, approximately neutral, stable, and in aspherical shape. Additionally, in vitro release data showed that the release of posaconazole from the micelles was higher than that of suspension. Conclusion: The results revealed that the optimized micellar formulation of posaconazole offers a potential approach for topical ocular administration.

Biodegradable polymers-based nanoparticles to enhance the antifungal efficacy of fluconazole against Candida albicans

2021 ◽  
Vol 22 ◽  
Author(s):  
Noha Saleh ◽  
Soha Elshaer ◽  
Germeen Girgis
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Encapsulation Efficiency ◽  
Water Solubility ◽  
In Vitro Release ◽  
Double Emulsion ◽  
Dilution Method ◽  
Ft Ir ◽  
Antifungal Efficacy

Background: Fluconazole (FLZ), a potent antifungal medication, is characterized by poor water solubility that reduced its antifungal efficacy. Objective: This study aimed to prepare FLZ-loaded polymeric nanoparticles (NPs) by using different polymers and techniques as a mean of enhancing the antifungal activity of FLZ. Methods: NP1, NP2, and NP3 were prepared by the double emulsion/solvent evaporation method using PLGA, PCL, and PLA, respectively. The ionotropic pre-gelation technique was applied to prepare an alginate/chitosan-based formulation (NP4). Particle size, zeta potential, encapsulation efficiency, and loading capacity were characterized. FT-IR spectra of FLZ, the polymers, and the prepared NPs were estimated. NP4 was selected for further in-vitro release evaluation. The broth dilution method was used to assess the antifungal activity of NP4 using a resistant clinical isolate of Candida albicans. Results: The double emulsion method produced smaller-sized particles (<390 nm) but with much lower encapsulation efficiency (< 12%). Alternatively, the ionic gelation method resulted in nanosized particles with a markedly higher encapsulation efficiency of about 40%. The FT-IR spectroscopy confirmed the loading of the FLZ molecules in the polymeric network of the prepared NPs. The release profile of NP4 showed a burst initial release followed by a controlled pattern up to 24 hours with a higher percent released relative to the free FLZ suspension. NP4 was able to reduce the value of MIC of FLZ by 20 times. Conclusion: The antifungal activity of FLZ against C. albicans was enhanced markedly via its loading in the alginate/chitosan-based polymeric matrix of NP4.

Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the management of Schizophrenia

2021 ◽  
Vol 14 ◽  
Author(s):  
Sarbjot Kaur ◽  
Ujjwal Nautiyal ◽  
Pooja A. Chawla ◽  
Viney Chawla
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Nanostructured Lipid Carriers ◽  
Polydispersity Index ◽  
Poloxamer 407 ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Vitro Release

Background: Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain. Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia. Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out. Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460 respectively. The encapsulation efficiency of formulation S6 was found to be 87.25 %. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96 % respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%. Conclusion: These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for treatment of schizophrenia.

scholarly journals Enhanced Lymphatic Delivery of Methotrexate Using W/O/W Nanoemulsion: In Vitro Characterization and Pharmacokinetic Study

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 978 ◽  
Author(s):  
Ji-Hun Jang ◽  
Seung-Hyun Jeong ◽  
Yong-Bok Lee
Keyword(s):  
Plasma Concentration ◽  
Zeta Potential ◽  
Intravenous Administration ◽  
Half Life ◽  
Encapsulation Efficiency ◽  
In Vitro Release ◽  
Lymphatic Delivery ◽  
Vitro Release ◽  
Lymphatic Targeting

Methotrexate, which is widely used in the treatment of cancer and immune-related diseases, has limitations in use because of its low bioavailability, short half-life, and tissue toxicity. Thus, in this study, a nano-sized water-in-oil-in-water (W/O/W) double emulsion containing methotrexate was prepared to enhance its lymphatic delivery and bioavailability. Based on the results from solubility testing and a pseudo-ternary diagram study, olive oil as the oil, Labrasol as a surfactant, and ethanol as a co-surfactant, were selected as the optimal components for the nanoemulsion. The prepared nanoemulsion was evaluated for size, zeta potential, encapsulation efficiency, pH, morphology, and in vitro release profiles. Furthermore, pharmacokinetics and lymphatic targeting efficiency were assessed after oral and intravenous administration of methotrexate-loaded nanoemulsion to rats. Mean droplet size, zeta potential, encapsulation efficiency, and pH of formulated nanoemulsion were 173.77 ± 5.76 nm, −35.63 ± 0.78 mV, 90.37 ± 0.96%, and 4.07 ± 0.03, respectively. In vitro release profile of the formulation indicated a higher dissolution and faster rate of methotrexate than that of free drug. The prepared nanoemulsion showed significant increases in maximum plasma concentration, area under the plasma concentration-time curve, half-life, oral bioavailability, and lymphatic targeting efficiency in both oral and intravenous administration. Therefore, our research proposes a methotrexate-loaded nanoemulsion as a good candidate for enhancing targeted lymphatic delivery of methotrexate.

scholarly journals Formulation of Nanomicelles to Improve the Solubility and the Oral Absorption of Silymarin

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1688 ◽  
Author(s):  
Vieri Piazzini ◽  
Mario D’Ambrosio ◽  
Cristina Luceri ◽  
Lorenzo Cinci ◽  
Elisa Landucci ◽  
...  
Keyword(s):  
Encapsulation Efficiency ◽  
Oral Absorption ◽  
Drug Loading ◽  
Antioxidant Properties ◽  
Aqueous Solubility ◽  
Average Diameter ◽  
Critical Micellar Concentration ◽  
Polydispersity Index ◽  
Vitamin E Tpgs

Two novel nanomicellar formulations were developed to improve the poor aqueous solubility and the oral absorption of silymarin. Polymeric nanomicelles made of Soluplus and mixed nanomicelles combining Soluplus with d-α-tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS) were prepared using the thin film method. Physicochemical parameters were investigated, in particular the average diameter, the homogeneity (expressed as polydispersity index), the zeta potential, the morphology, the encapsulation efficiency, the drug loading, the critical micellar concentration and the cloud point. The sizes of ~60 nm, the narrow size distribution (polydispersity index ≤0.1) and the encapsulation efficiency >92% indicated the high affinity between silymarin and the core of the nanomicelles. Solubility studies demonstrated that the solubility of silymarin increased by ~6-fold when loaded into nanomicelles. Furthermore, the physical and chemical parameters of SLM-loaded formulations stored at room temperature and in refrigerated conditions (4 °C) were monitored over three months. In vitro stability and release studies in media miming the physiological conditions were also performed. In addition, both formulations did not alter the antioxidant properties of silymarin as evidenced by the 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) assay. The potential of the nanomicelles to increase the intestinal absorption of silymarin was firstly investigated by the parallel artificial membrane permeability assay. Subsequently, transport studies employing Caco-2 cell line demonstrated that mixed nanomicelles statistically enhanced the permeability of silymarin compared to polymeric nanomicelles and unformulated extract. Finally, the uptake studies indicated that both nanomicellar formulations entered into Caco-2 cells via energy-dependent mechanisms.

scholarly journals FORMULATION DEVELOPMENT AND EVALUATION OF PRONIOSOMAL GEL OF ETHINYLESTRADIOL AND LEVONORGESTREL FOR ANTIFERTILITY TREATMENT

2019 ◽  
Vol 12 (1) ◽  
pp. 364
Author(s):  
Shikha Baghel Chauhan ◽  
Tanveer Naved ◽  
Nayyar Parvez
Keyword(s):  
Optical Microscopy ◽  
Encapsulation Efficiency ◽  
In Vitro Release ◽  
Stability Studies ◽  
Formulation Development ◽  
Promising Alternative ◽  
Size And Shape ◽  
Permeation Studies ◽  
Gel Formulations

Objective: The purpose of this research was to develop and formulate proniosomal gel drug delivery system of ethinylestradiol and levonorgestrel for antifertility treatment that is capable of efficiently delivering entrapped drug over an extended period of time.Methods: Ethinylestradiol and levonorgestrel are encapsulated in various formulations of proniosomal gel composed of various ratios of span surfactant, cholesterol, soya lecithin, and alcohol as aqueous phase prepared by coacervation-phase separation method. The prepared formulations characterized for drug encapsulation efficiency, size distribution, in vitro release studies, and vesicular stability at different storage conditions were carried. Stability studies for proniosomal gel were carried out for a few weeks. Morphological size and shape of the vesicles are characterized using optical microscopy and scanning electron microscopy (SEM). Stability studies for proniosomal gel were carried out for 3 months.Results: Morphological size and shape of the vesicles are characterized using optical microscopy and SEM, particles are found to be spherical, size of the particles is in the range of 46.4–80.6 nm, and permeation studies showed good control release for prolonged period of time. The encapsulation efficiency of proniosomal gel formulations is in the range of 74–80% and in vitro permeation studies proved that good amount of drug is permeated and has reasonably good stability characteristics as well.Conclusions: The results suggest that proniosomal gel formulations of ethinylestradiol and levonorgestrel may be used for transdermal delivery for antifertility treatment. The dried proniosomal formulation could act as a promising alternative to niosomes.

scholarly journals Microencapsulation of Thymol in Poly(lactide-co-glycolide) (PLGA): Physical and Antibacterial Properties

Materials ◽  
2019 ◽  
Vol 12 (7) ◽  
pp. 1133 ◽  
Author(s):  
Zhu Zhu ◽  
Tiantian Min ◽  
Xueji Zhang ◽  
Yongqiang Wen
Keyword(s):  
Storage Stability ◽  
In Vitro Release ◽  
Antibacterial Properties ◽  
Spherical Shape ◽  
Food Preservative ◽  
And Storage ◽  
Fast Release ◽  
Vitro Release ◽  
And Staphylococcus Aureus

Thymol has been shown to be a safe and effective broad-spectrum antimicrobial agent that can be used as a food preservative. However, its volatile characteristics and strong odor limit its use in food products. The microencapsulation of this essential oil in biopolymers could overcome these disadvantages. In this work, thymol-loaded poly(lactide-co-glycolide) (PLGA) microparticles were successfully prepared and the optimal encapsulation efficiency was obtained at 20% (w/w) thymol. Microparticles containing thymol presented a spherical shape and smooth surface. Microencapsulation significantly improved the thermal and storage stability of thymol. In vitro release profiles demonstrated an initial fast release followed by a slow and sustained release. Thymol-loaded microparticles had strong antibacterial activity against Escherichia coli and Staphylococcus aureus, and the effectiveness of their antibacterial properties was confirmed in a milk test. Therefore, the thymol-loaded microparticles show great potential for use as an antimicrobial and as preservation additives in food.

Development and Characterization of Olanzapine Loaded Poly(lactide-co-glycolide) Microspheres for Depot Injection: In vitro and In vivo Release Profiles

2019 ◽  
Vol 16 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Fahad Pervaiz ◽  
Mahmood Ahmad ◽  
Lihong Li ◽  
Ghulam Murtaza
Keyword(s):  
Bulk Density ◽  
Encapsulation Efficiency ◽  
In Vitro Release ◽  
Infrared Spectrometry ◽  
Burst Release ◽  
In Vivo Release ◽  
Depot Injection ◽  
Vitro Release

Purpose: The purpose of this study was to develop a new PLGA based microsphere formulation aimed to release the olanzapine for the period of one month which will result in increased compliance. Methods: Microspheres loaded with olanzapine were prepared using oil in water emulsion and solvent evaporation technique. The microspheres were characterized by surface morphology, shape, size, bulk density, encapsulation efficiency, and Fourier transform infrared spectrometry. In vitro release studies were performed in phosphate buffer at 37°C and in vivo studies were conducted on male Sprague- Dawley rats. Results: The morphological results indicated that microspheres produced were having a smooth surface, spherical shape and the size in the range from 9.71 to 19.90 μm mean diameter. Encapsulation efficiency of olanzapine loaded microspheres was in the range of 78.53 to 96.12% and was affected by changing the ratio of lactic to glycolic acid in copolymer PLGA. The properties of PLGA and other formulation parameters had a significant impact on in vitro and in vivo release of drug from microspheres. In vitro release kinetics revealed that release of drug from microspheres is by both non-Fickian diffusion and erosion of PLGA polymer. In vivo data indicated an initial burst release and then sustained release depending on properties of PLGA, microsphere size, and bulk density. Conclusion: This study indicates that microsphere formulations developed with PLGA (75:25) and PLGA (85:15) have provided a sufficient steady release of drug for at least 30 days and can be potential candidates for 30-day depot injection drug delivery of olanzapine.

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