scholarly journals Targeted Delivery of Amantadine-loaded Methacrylate Nanosphere-ligands for the Potential Treatment of Amyotrophic Lateral Sclerosis

2018 ◽  
Vol 21 ◽  
pp. 94-109 ◽  
Author(s):  
Zamanzima Mazibuko ◽  
Sunaina Indermun ◽  
Mershen Govender ◽  
Pradeep Kumar ◽  
Lisa C Du Toit ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Zeta Potential ◽  
Targeted Delivery ◽  
Ex Vivo ◽  
Release Kinetics ◽  
Burst Release ◽  
Prolonged Release ◽  
Chelating Ligand ◽  
Study Results ◽  
Lateral Sclerosis

Purpose. This study aimed to develop and analyse poly(DL-lactic acid)-methacrylic acid nanospheres bound to the chelating ligand diethylenetriaminepentaacetic acid (DTPA)  for the targeted delivery of amantadine in Amyotrophic Lateral Sclerosis (ALS). Methods. The nanospheres were prepared by a double emulsion solvent evaporation technique statistically optimized employing a 3-Factor Box-Behnken experimental design. Analysis of the particle size, zeta potential, polydispersity (Pdl), morphology, drug entrapment and drug release kinetics were carried out. Results. The prepared nanospheres were determined to have particle sizes ranging from 68.31 to 113.6 nm (Pdl ≤ 0.5). An initial burst release (50% of amantadine released in 24 hr) was also obtained, followed by a prolonged release phase of amantadine over 72 hr. Successful conjugation of the chelating ligand onto the surface of the optimised nanospheres was thereafter achieved and confirmed by TEM. The synthesized modified nanospheres were spherical in shape, 105.6 nm in size, with a PdI of 0.24 and zeta potential of -28.0 mV. Conjugation efficiency was determined to be 74%. In vitro and ex vivo cell study results confirmed the intracellular uptake of the modified nanospheres by the NSC-34 cell line and the non-cytotoxicity of the synthesized nanospheres. Conclusions. Biocompatible amantadine-loaded nanospheres were successfully designed, characterized and optimized employing the randomized Box-Behnken statistical design. Delivery of amantadine over 72 hrs was achieved, with the nanospheres being of a size capable of internalization by the NSC- 34 cells. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Inulin-Grafted Stearate (In-g-St) as the Effective Self-Assembling Polymeric Micelle: Synthesis and Evaluation for the Delivery of Betamethasone

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Gholamabbas Chehardoli ◽  
Parham Norouzian ◽  
Farzin Firozian
Keyword(s):  
Zeta Potential ◽  
Sustained Release ◽  
Targeted Delivery ◽  
Encapsulation Efficiency ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Polymeric Micelle ◽  
Water Soluble ◽  
Burst Release ◽  
Potential Measurement

Background. Betamethasone as a corticosteroid drug is commonly used for the treatment of rheumatoid arthritis. Unfortunately, betamethasone is a low water-soluble drug and its efficacy is low. So an attractive strategy is the targeted delivery of betamethasone to the damaged joint using polymeric micelle-based carriers. Methods. Inulin-grafted stearate (In-g-St) was synthesized via the reaction of stearoyl chloride and inulin, then characterized by FT-IR and H-NMR. In-g-St forms micelles in the presence of betamethasone. The prepared polymeric micelles were characterized for size, zeta potential, drug loading, particles’ morphology, critical micelle concentration (CMC), and encapsulation efficiency. So sustained release polymeric micelles of betamethasone were developed by employing In-g-St. Results. The measurement of particle size showed a mean diameter of 60 and 130 nm for 10% and 20% drug-loaded micelles, respectively, and SEM showed that the particle’s morphologies are spherical. Zeta potential measurement for the drug-containing micelles showed a value of -11.8 mV. Drug loading efficiency and the encapsulation efficiency were 6.36% and 63.6%, as well as 18.97% and 94.88% for 10% and 20%, respectively. 20% drug-loaded polymer showed a small burst release of betamethasone at the first 3 h which was followed by sustained release in the next 24 h. Furthermore, the formula with 10% exhibited good sustained release properties except for the minor initial burst release. Conclusion. Data from the zeta potential, CMC, drug loading capacity, and in vitro drug release studies indicated that In-g-St polymeric micelles can be suitable candidates for the efficient delivery of hydrophobic drugs like betamethasone.

scholarly journals DEVELOPMENT AND CHARACTERIZATION OF INDOMETHACIN-LOADED MUCOADHESIVE NANOSTRUCTURED LIPID CARRIERS FOR TOPICAL OCULAR DELIVERY

2018 ◽  
Vol 10 (2) ◽  
pp. 91 ◽  
Author(s):  
Pattravee Niamprem ◽  
S. P. Srinivas ◽  
Waree Tiyaboonchai
Keyword(s):  
Ex Vivo ◽  
In Vitro Release ◽  
Tween 80 ◽  
Nanostructured Lipid Carriers ◽  
Burst Release ◽  
Prolonged Release ◽  
Polyethylene Glycol 400 ◽  
Safe Delivery ◽  
Vitro Release

Objective: To develop and characterize indomethacin loaded-nanostructured lipid carriers (IND-NLCs) for topical ophthalmic delivery with different particle sizes and polymer coating to improve the mucoadhesive property on the ocular surface.Methods: Nanostructured lipid carriers (NLCs) with different solid lipids and surfactants were prepared by the high-pressure homogenization technique. The optimized IND-NLCs was coated with polyethylene glycol 400 (PEG). The physicochemical properties and entrapment efficacy (EE) were examined. In vitro release studies were investigated using the shake-flask method. Ex vivo mucoadhesive studies were assessed by the wash-off test. In addition, the cytotoxicity was assessed by the short time exposure test.Results: IND-NLCs of ~300 and ~40 nm in diameter were successfully produced with a zeta potential of -30 mV and EE of 60–70 %. IND-NLCs prepared with Tween 80 as surfactant could be sterilized by autoclaving. The PEG coating of IND-NLCs did not affect either the particle size or EE. In vitro release showed a prolonged release for 360 min with a burst release of 50-60% occurring within 5 min. The smaller-sized IND-NLCs showed slightly faster release rates and better mucoadhesion to cornea compared to the larger IND-NLCs. PEG-coated IND-NLCs showed the highest mucoadhesion. In addition, IND-NLCs showed less cytotoxicity compared to IND alone. Conclusion: The small and PEG-coated NLCs represents a potentially useful carrier for safe delivery of indomethacin to the ocular surface with increased residence time.

scholarly journals Implication of 5-HT in the Dysregulation of Chloride Homeostasis in Prenatal Spinal Motoneurons from the G93A Mouse Model of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 21 (3) ◽  
pp. 1107 ◽  
Author(s):  
Elodie Martin ◽  
William Cazenave ◽  
Anne-Emilie Allain ◽  
Daniel Cattaert ◽  
Pascal Branchereau
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
High Performance ◽  
Clinical Symptoms ◽  
Ex Vivo ◽  
Lumbar Spinal Cord ◽  
Spinal Motoneurons ◽  
Chloride Homeostasis ◽  
Lumbar Spinal ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. The early presymptomatic onset of abnormal processes is indicative of cumulative defects that ultimately lead to a late manifestation of clinical symptoms. It remains of paramount importance to identify the primary defects that underlie this condition and to determine how these deficits lead to a cycle of deterioration. We recently demonstrated that prenatal E17.5 lumbar spinal motoneurons (MNs) from SOD1G93A mice exhibit a KCC2-related alteration in chloride homeostasis, i.e., the EGABAAR is more depolarized than in WT littermates. Here, using immunohistochemistry, we found that the SOD1G93A lumbar spinal cord is less enriched with 5-HT descending fibres than the WT lumbar spinal cord. High-performance liquid chromatography confirmed the lower level of the monoamine 5-HT in the SOD1G93A spinal cord compared to the WT spinal cord. Using ex vivo perforated patch-clamp recordings of lumbar MNs coupled with pharmacology, we demonstrated that 5-HT strongly hyperpolarizes the EGABAAR by interacting with KCC2. Therefore, the deregulation of the interplay between 5-HT and KCC2 may explain the alteration in chloride homeostasis detected in prenatal SOD1G93A MNs. In conclusion, 5-HT and KCC2 are two likely key factors in the presymptomatic phase of ALS, particular in familial ALS involving the SOD1G93A mutation.

scholarly journals Antimicrobial Formulations of Absorbable Bone Substitute Materials as Drug Carriers Based on Calcium Sulfate

2016 ◽  
Vol 60 (7) ◽  
pp. 3897-3905 ◽  
Author(s):  
D. Pförringer ◽  
A. Obermeier ◽  
M. Kiokekli ◽  
H. Büchner ◽  
S. Vogt ◽  
...  
Keyword(s):  
Bone Substitute ◽  
Ex Vivo ◽  
Release Kinetics ◽  
Drug Carriers ◽  
Prolonged Release ◽  
Clinical Parameters ◽  
Bone Substitute Materials ◽  
Substitute Materials

ABSTRACTSubstitution of bones is a well-established, necessary procedure to treat bone defects in trauma and orthopedic surgeries. For prevention or treatment of perioperative infection, the implantation of resorbable bone substitute materials carrying antibiotics is a necessary treatment. In this study, we investigated the newly formulated calcium-based resorbable bone substitute materials containing either gentamicin (CaSO4-G [Herafill-G]), vancomycin (CaSO4-V), or tobramycin (Osteoset). We characterized the released antibiotic concentration per unit. Bone substitute materials were implanted in bones of rabbits via a standardized surgical procedure. Clinical parameters and levels of the antibiotic-releasing materials in serum were determined. Local concentrations of antibiotics were measured using antimicrobial tests of bone tissue. Aminoglycoside release kineticsin vitroper square millimeter of bead surface showed the most prolonged release for gentamicin, followed by vancomycin and, with the fastest release, tobramycin.In vivolevel in serum detected over 28 days was highest for gentamicin at 0.42 μg/ml, followed by vancomycin at 0.11 μg/ml and tobramycin at 0.04 μg/ml. The clinical parameters indicated high biocompatibility for materials used. None of the rabbits subjected to the procedure showed any adverse reaction. The highest availability of antibiotics at 14.8 μg/g on day 1 in the cortical tibiaex vivowas demonstrated for gentamicin, decreasing within 14 days. In the medulla, vancomycin showed a high level at 444 μg/g on day 1, decreasing continuously over 14 days, whereas gentamicin decreased faster within the initial 3 days. The compared antibiotic formulations varied significantly in release kinetics in serum as well as locally in medulla and cortex.

scholarly journals Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design:In VitroandIn VivoEvaluation

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Deepak Sharma ◽  
Dipika Maheshwari ◽  
Gilphy Philip ◽  
Ravish Rana ◽  
Shanu Bhatia ◽  
...  
Keyword(s):  
Drug Release ◽  
Zeta Potential ◽  
Cell Viability ◽  
Ex Vivo ◽  
Burst Release ◽  
Release Behavior ◽  
Sprague Dawley ◽  
Drug Release Behavior ◽  
Biodistribution Studies

The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is,z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape withz-average 167–318 d·nm, PDI below 0.441, and −18.4 mV zeta potential with maximum % drug entrapment of 90.1%.In vitrodrug release behavior followed Korsmeyer-Peppas model and showed initial burst release of21.7±1.3%with prolonged drug release of69.5±0.8%from optimized NPs up to 24 h.In vitrodrug release data was found in agreement withex vivopermeation data through sheep nasal mucosa.In vitrocell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway.

Efavirenz–eudragit E-100 nanoparticle-loaded aerosol foam for sustained release: in-vitro and ex-vivo evaluation

2015 ◽  
Vol 69 (2) ◽  
Author(s):  
B. N. Vedha Hari ◽  
N. Narayanan ◽  
K. Dhevedaran
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Ex Vivo ◽  
Release Kinetics ◽  
Morphological Properties ◽  
Foam Formulation ◽  
Drug Content ◽  
Release Studies ◽  
Grade One

AbstractThe control of HIV infection using antiretroviral agents, especially through targeted delivery, has attracted extensive attention in the last decade. Recently, the vaginal route of administration has become the one most recommended for HIV infections during pregnancy. Efavirenz is a non-nucleoside reverse transcriptase inhibitor anti-HIV drug and its prolonged half-life helps achieve long-term preexposure prophylaxis of HIV-1 infections; it is used as a first-line drug in the treatment using combination therapy. Nanotechnology has received attention as a major area of research into drug delivery in recent years. The aerosol foam formulation is packed under pressure and contains therapeutically active ingredients that are released as foam on the activation of an appropriate valve system. The objective of this study was to develop an aerosol foam formulation of efavirenz nanoparticles for vaginal drug delivery. The nanoparticles were prepared using the emulsion solvent evaporation method and converted into an aerosol foam formulation with the addition of 0.1 mass % of sodium lauryl sulphate as a foaming agent and pressurised with 1,1,1,2-tetrafluroethane. The nanoparticles containing the formulation and aerosol foam formulation were individually characterised by applying various tests such as particle size, zeta potential, pH, viscosity, drug content, entrapment efficiency, drug release studies and release kinetics. The compatibility of the materials was evaluated using FT-IR, polymorphic changes by TGA-DSC and also the morphological properties using SEM study. Foam density, bubble size and collapse time were evaluated in the aerosol-foam formulation; in addition, the drug content and release studies were compared with nanoparticle formulation. The results revealed that the nanoparticle-containing formulation and aerosol formulations were stable and the foam emerged as grade one with fine bubbles and became coarser over time.

scholarly journals Correlations Between Median Nerve Sonography and Conduction Study Results and Functional Scales in Amyotrophic Lateral Sclerosis

2020 ◽  
Author(s):  
Parvaneh Deilami ◽  
Shadi Ghourchian ◽  
Bahram Haghi Ashtiani ◽  
Sara Esmaeili ◽  
Maryam Bahadori ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Median Nerve ◽  
Rating Scale ◽  
Normal Population ◽  
Compound Muscle Action Potential ◽  
Cross Sectional ◽  
Study Results ◽  
Significant Difference ◽  
Als Patients ◽  
Lateral Sclerosis

We aimed to compare the sonographic measurement of median nerve cross-section area (CSA) in patients with Amyotrophic Lateral Sclerosis (ALS) and healthy individuals. The effect of duration of the disease on correlations between paraclinical findings and ALS functional rating scale (ALSFRS) were secondarily aimed to be evaluated. The cross-sectional study was approved by the Ethical Committee of Iran University of Medical Sciences and conducted between January 2017 and December 2018. We evaluated the median nerve surface area by means of sonography in 35 ALS patients and 35 healthy controls. Compound muscle action potential (CMAP) amplitudes during nerve conduction study and ALSFRS were recorded by the same trained specialist. Data were analyzed using SPSS software version 18. We did not find a significant difference between CSA in ALS patients and the normal population (P>0.05). Comparing to normal individuals, the mean CMAP decreased significantly in ALS patients (6.6±3.07 mV versus 10.25±2.2 mV, P<0.001). ALSFRS correlated with both CSA of the median nerve at the wrist (P:<0.001, r:0.78) and the CMAP (P:<0.001, r:0.74) that were confirmed by regression models designed to consider the effect of disease duration on these correlations. CSA was not different between ALS patients and the normal population, but CMAP decreased in ALS patients. ALSFRS correlated with both CSA and CMAP of the median nerve.

scholarly journals IN VITRO IN VIVO EVALUATION OF NIOSOMAL FORMULATION OF FAMOTIDINE

2020 ◽  
pp. 15-22
Author(s):  
RIZWANA KHAN ◽  
RAGHUVEER IRCHHAIYA
Keyword(s):  
Drug Delivery ◽  
Zeta Potential ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Pharmacological Action ◽  
In Vivo Study ◽  
Compatibility Study ◽  
Prolonged Release

Objective: The present study was aimed on formulation and evaluation of famotidine loaded niosomal formulation for in vitro and in vivo pharmacokinetic behaviour. Formulating it as niosomal formulation might be quite advantageous for prolonging the duration of pharmacological action and improved bioavailability. Methods: In the present study niosomal formulations were prepared by using most documented thin film hydration technique by using various grades of surfactants (span 20, 40, 60, 80) in varying ratios with cholesterol, negative charge inducer di cetyl phosphate (DCP) and drug famotidine. Suitable preformulation studies were conducted like identification of drug, excipient and drug compatibility study. The optimized drug loaded niosomes were characterized for size and morphology, polydispersity index, zeta potential, drug entrapment, in vitro release, in vivo study and stability study. Results: The results showed that the vesicles formed were spherical in shape, size ranging between 160.1 nm to 718.7 nm with zeta potential values indicating good stability and formulation containing span 60 (NMS7) showed the highest entrapment efficiency (73.234%). All the formulations showed prolonged release profile for more than 24 h with release kinetics better suited to zero order release pattern. In vivo study conducted on rabbits predicted a fourfold increase in pharmacokinetic parameter (area under curve)AUC and pharmacological action for more than 24 h as compared to free drug famotidine which showed its action only upto 12 h. Conclusion: Thus the famotidine loaded niosomal formulation may be considered as a very promising drug delivery system which could be successfully employed for prolonging the drug release and overcoming the drawbacks of conventional drug delivery systems.

scholarly journals Design, Formulation, In-Vitro and Ex-Vivo Evaluation of Atazanavir Loaded Cubosomal Gel

2020 ◽  
Vol 11 (4) ◽  
pp. 12037-12054
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Relative Bioavailability ◽  
Transdermal Application ◽  
Study Results ◽  
Nano Formulation

In this study, Atazanavir (ATZ) was designed into the Nano formulation called cubosomes to improve its bioavailability and curtail the adverse effects by the transdermal route delivery of ATZ -loaded cubosomes. Around twenty cubosomal formulations were formulated using a Central composite factorial design. The effect of glyceryl monooleate (GMO), surfactant (Pluronic F 127), and Cetyltrimethylammonium bromide (CTAB) were studied using processes of emulsification and homogenization. Different concentrations of independent variables on particle size distribution, zeta potential, and entrapment efficiency were determined. FTIR, DSC, X-ray, and SEM, TEM results established that the drug was encapsulated in the cubosomes. The results suggested that the optimal formula exhibited a particle size of 100±7.9 - 345±6.4 nm and entrapment efficiency ranging from 61±4.6 - 93±0.8, zeta potential values ranging from -24.51 to -32.45 mV, polydispersity index values ranged from 0.35±0.01-0.54±0.02 of ATZ. The in vitro studies showed a controlled release pattern of drug release up to 24h. The ATZ cubosomal gel application on the in vivo absorption studies of the drug was studied in rats and compared with oral ATZ solution. The in vivo study results showed that the transdermal application of ATZ cubosomal gel considerably improves the absorption of drug compared to that of oral ATZ solution and found that the relative bioavailability is 4.6 times greater of oral ATZ solution. Thus it can be concluded that the ATZ cubosomal gel application via transdermal delivery route has the potential in increasing the bioavailability of the drug.

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