scholarly journals Ovarian Accumulation of Nanoemulsions: Impact of Mice Age and Particle Size

2021 ◽  
Vol 22 (15) ◽  
pp. 8283
Author(s):  
Eike Folker Busmann ◽  
Julia Kollan ◽  
Karsten Mäder ◽  
Henrike Lucas
Keyword(s):  
Particle Size ◽  
Ex Vivo ◽  
Reticuloendothelial System ◽  
Systematic Investigation ◽  
Measured Signal ◽  
Reproductive Aging ◽  
Sex Steroid Hormone ◽  
Adult Mice ◽  
Radiant Efficiency

Nanotechnology in the field of drug delivery comes with great benefits due to the unique physicochemical properties of newly developed nanocarriers. However, they may come as well with severe toxicological side effects because of unwanted accumulation in organs outside of their targeted site of actions. Several studies showed an unintended accumulation of various nanocarriers in female sex organs, especially in the ovaries. Some led to inflammation, fibrosis, or decreasing follicle numbers. However, none of these studies investigated ovarian accumulation in context to both reproductive aging and particle size. Besides the influences of particle size, the biodistribution profile may be altered as well by reproductive aging because of reduced capacities of the reticuloendothelial system (RES), changes in sex steroid hormone levels as well as altering ovarian stromal blood flow. This systematic investigation of the biodistribution of intravenously (i.v) injected nanoemulsions revealed significant dependencies on the two parameters particle size and age starting from juvenile prepubescent to senescent mice. Using fluorescent in vivo and ex vivo imaging, prepubescent mice showed nearly no accumulation of nanoemulsion in their uteri and ovaries, but high accumulations in the organs of the RES liver and spleen independently of the particle size. In fertile adult mice, the accumulation increased significantly in the ovaries with an increased particle size of the nanoemulsions by nearly doubling the portion of the average radiant efficiency (PARE) to ~10% of the total measured signal of all excised organs. With reproductive aging and hence loss of fertility in senescent mice, the accumulation decreased again to moderate levels, again independently of the particle size. In conclusion, the ovarian accumulation of these nanocarriers depended on both the age plus the particle size during maturity.

scholarly journals Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 197 ◽  
Author(s):  
Doaa Hassan ◽  
Rehab Abdelmonem ◽  
Menna Abdellatif
Keyword(s):  
Particle Size ◽  
Intraocular Pressure ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Molar Ratio ◽  
Duration Of Action ◽  
Corneal Permeability ◽  
Glaucoma Treatment

This study evaluated the efficacy of cationic nanoparticle (leciplex) to deliver carvedilol to ocular surface for glaucoma treatment as recent studies pointed out the effect of topical carvedilol on intraocular pressure, therefore carvedilol loaded leciplex formulae were prepared using soy phosphatidyl choline (SPC) and cationic surfactant (CTAB/DDAB) and characterized for morphology, entrapment efficiency, particle size, zeta potential and ex-vivo corneal permeation. Then the selected formula was evaluated via in-vivo studies in comparison with carvedilol solution. Leciplex nanoparticles appeared spherical in shape with entrapment efficiency exceeded 95% in all formulae. Leciplex formula composed of SPC and DDAB in (1:1) molar ratio showed the smallest particle size (16.04 ± 1.2 nm), highest zeta potential value (53.9 ± 0.91 mv) and highest apparent corneal permeability coefficient (0.1157 cm/h). Carvedilol leciplex reduced intraocular pressure (IOP) to normal range in ocular hypertensive rabbits after 30 min and duration of action lasted for 24 h, while carvedilol solution reduced IOP to normal value after 60 min and duration of action lasted for 6 h. Furthermore, histological examination of eyeballs of rabbits treated with carvedilol leciplex showed improvement of retinal atrophy of glaucomatous eyes. This study concluded that leciplex improve transcorneal permeation and bioavailability of carvedilol.

scholarly journals Nobiletin-loaded composite penetration enhancer vesicles restore the normal miRNA expression and the chief defence antioxidant levels in skin cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahitab Bayoumi ◽  
Mona G. Arafa ◽  
Maha Nasr ◽  
Omaima A. Sammour
Keyword(s):  
Particle Size ◽  
Skin Cancer ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Physical Stability ◽  
Entrapment Efficiency ◽  
Penetration Enhancer ◽  
Oxidative Stress Biomarkers ◽  
Skin Deposition

AbstractSkin cancer is one of the most dangerous diseases, leading to massive losses and high death rates worldwide. Topical delivery of nutraceuticals is considered a suitable approach for efficient and safe treatment of skin cancer. Nobiletin; a flavone occurring in citrus fruits has been reported to inhibit proliferation of carcinogenesis since 1990s, is a promising candidate in this regard. Nobiletin was loaded in various vesicular systems to improve its cytotoxicity against skin cancer. Vesicles were prepared using the thin film hydration method, and characterized for particle size, zeta potential, entrapment efficiency, TEM, ex-vivo skin deposition and physical stability. Nobiletin-loaded composite penetration enhancer vesicles (PEVs) and composite transfersomes exhibited particle size 126.70 ± 11.80 nm, 110.10 ± 0.90 nm, zeta potential + 6.10 ± 0.40 mV, + 9.80 ± 2.60 mV, entrapment efficiency 93.50% ± 3.60, 95.60% ± 1.50 and total skin deposition 95.30% ± 3.40, 100.00% ± 2.80, respectively. These formulations were selected for cytotoxicity study on epidermoid carcinoma cell line (A431). Nobiletin-loaded composite PEVs displayed the lowest IC50 value, thus was selected for the in vivo study, where it restored skin condition in DMBA induced skin carcinogenesis mice, as delineated by histological and immuno-histochemical analysis, biochemical assessment of skin oxidative stress biomarkers, in addition to miRNA21 and miRNA29A. The outcomes confirmed that nobiletin- loaded composite PEVs is an efficient delivery system combating skin cancer.

scholarly journals FORMULATION AND OPTIMIZATION OF QUERCETIN LOADED NANOSPONGES TOPICAL GEL: EX VIVO, PHARMACODYNAMIC AND PHARMACOKINETIC STUDIES

2019 ◽  
pp. 156-165
Author(s):  
Y. SARAH SUJITHA ◽  
Y. INDIRA MUZIB
Keyword(s):  
Particle Size ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Hydroxypropyl Methylcellulose ◽  
Entrapment Efficiency ◽  
Diffusion Method ◽  
Pharmacokinetic Studies ◽  
Topical Gel

Objective: Quercetin is therapeutically hampered because of its poor solubility. The present investigation was aimed to prepare quercetin loaded nanosponges topical gel to enhance the solubility and efficacy of the drug. Methods: Quercetin nanosponges were prepared by emulsion solvent diffusion method. Developed nanosponges optimized by particle size, SEM, entrapment efficiency, FT-IR, DSC, P-XRD, In vitro studies. The optimized formulation of nanosponges was loaded into a topical gel and it was characterized by ex-vivo, in vivo Pharmacodynamic and kinetic studies. Results: The particle size and zeta potential of optimized nanosponges were found to be 188.3 nm and-0.1mV. Surface morphology was studied using SEM Analysis which showed tiny sponge-like structure and entrapment efficiency was found to be 96.5 %. In vitro drug release of optimized nanosponges was found to be 98.6% for 7hours. Optimized nanosponges entrapped gel was prepared by using carbopol 934 and hydroxypropyl methylcellulose as gelling agents. The prepared nanogels were homogenous and ex-vivo skin permeation studies of the optimized nanosponges gel was found to be 98.1% for 5 h, quercetin loaded nanosponges has shown higher skin permeation efficiency (18.4µg/cm2±2.1) compared to pure quercetin gel. The pharmacokinetic and pharmacodynamic studies showed that the quercetin loaded nanosponges has shown more effective when compared to marketed formulation. Conclusion: Quercetin loaded nanosponges gel has shown a significant increase in activity (p<0.05) compared to the marketed formulation (Voveran Emulgel).

scholarly journals Gestational low-dose BPA exposure impacts suprachiasmatic nucleus neurogenesis and circadian activity with transgenerational effects

2021 ◽  
Vol 7 (22) ◽  
pp. eabd1159
Author(s):  
Dinushan Nesan ◽  
Kira M. Feighan ◽  
Michael C. Antle ◽  
Deborah M. Kurrasch
Keyword(s):  
Social Interactions ◽  
Suprachiasmatic Nucleus ◽  
Low Dose ◽  
Ex Vivo ◽  
Neural Progenitors ◽  
Fetal Exposure ◽  
Circadian Activity ◽  
Adult Mice ◽  
Physiological Processes

Critical physiological processes such as sleep and stress that underscore health are regulated by an intimate interplay between the endocrine and nervous systems. Here, we asked how fetal exposure to the endocrine disruptor found in common plastics, bisphenol A (BPA), causes lasting effects on adult animal behaviors. Adult mice exposed to low-dose BPA during gestation displayed notable disruption in circadian activity, social interactions, and associated neural hyperactivity, with some phenotypes maintained transgenerationally. Gestational BPA exposure increased vasopressin+ neurons in the suprachiasmatic nucleus (SCN), the region that regulates circadian rhythms, of F1 and F3 generations. Mechanistically, BPA increased proliferation of hypothalamic neural progenitors ex vivo and caused precocious neurogenesis in vivo. Co-antagonism of both estrogen and androgen receptors was necessary to block BPA’s effects on hypothalamic neural progenitors, illustrating a dual role for these endocrine targets. Together, gestational BPA exposure affects development of circadian centers, with lasting consequences across generations.

scholarly journals Ex Vivo Diffusion Tensor Imaging and Neuropathological Correlation in a Murine Model of Hypoxia–Ischemia-Induced Thrombotic Stroke

2010 ◽  
Vol 31 (4) ◽  
pp. 1155-1169 ◽  
Author(s):  
Ahmed Shereen ◽  
Niza Nemkul ◽  
Dianer Yang ◽  
Faisal Adhami ◽  
R Scott Dunn ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Internal Capsule ◽  
Diffusion Anisotropy ◽  
Rapid Reduction ◽  
Adult Mice ◽  
Hypoxia Ischemia ◽  
High Level

Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia–ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24 hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.

Dermal Delivery of Meloxicam Nanosuspensions based Gel: Optimization with Box Behnken Design Experiment Approach: Ex Vivo and In Vivo Study

2020 ◽  
Vol 10 (6) ◽  
pp. 766-777
Author(s):  
Inayat B. Pathan ◽  
Mahesh Sakhare ◽  
Wahid Ambekar ◽  
Chitral M. Setty
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Skin Irritation ◽  
Oral Route ◽  
Stability Study ◽  
In Vivo Study ◽  
Therapeutic Effects ◽  
Box Behnken Design

Background: Transdermal delivery of meloxicam is advantageous than the oral route in the treatment of pain management. Objective: The goal of the present study is to formulate and evaluate meloxicam (MX) loaded nanosuspensions based gel for transdermal application. Methods: The formulation parameters were optimized using Box Behnken design (BBD) taking three independent variables and three responses. Formulations were evaluated for particle size (nm), polydispersity index (PDI), zeta potential (mV), ex vivo permeation, in vivo study, morphology, FTIR, skin irritation and, stability study. Optimized formulation having Poloxamer 188 (0.4 mg), PVP K30 (0.5 mg) and sonication time (60 min.) demonstrated smaller particle size (159.2 ± 3.5 nm), low PDI (0.120 ± 0.01) and higher zeta potential value (-29 ± 4mV). Results: In the ex vivo study, MX-NG showed a significant increase (p<0.05) in the flux (24.40 ± 2.6 μg/cm2/h) of meloxicam through the human cadaver skin as compared to other formulations. In the in- vivo study, MX-NG showed a significant (p<0.05) increase in anti-inflammatory activity as compared to marketed gel. Conclusion: Thus, it is concluded that the developed meloxicam loaded nanosuspensions based gel showed maximum therapeutic effects in rats.

scholarly journals ENHANCED INTESTINAL ABSORPTION AND BIOAVAILABILITY VIA PRONIOSOMES FOR BAZEDOXIFENE ACETATE DRUG

2020 ◽  
pp. 31-42
Author(s):  
SMITHA GANDRA
Keyword(s):  
Particle Size ◽  
Oral Bioavailability ◽  
Ex Vivo ◽  
Angle Of Repose ◽  
In Vivo Studies ◽  
In Vitro Dissolution ◽  
Ionic Surfactant ◽  
Enhanced Absorption ◽  
Span 60

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and intestinal permeability. Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 60 and cholesterol ratio in the range of 0.8:0.2 to 0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug: span 60 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies. Results: Physico-chemical studies among various formulations helped in optimization of batch. Good flow properties confirmed from angle of repose values indicate easy filling into capsules. Enhancement in dissolution is due to incorporation of bazedoxifene acetate into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Solid state characterization studies prove the transformation to amorphous form with small particle size improving permeation. No drug excipient interaction was observed and sample is stable in refrigerated conditions. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control. Invivo studies proved enhanced absorption of bazedoxifene acetate drug by oral route. Conclusion: In conclusion, proniosomes provide a powerful and functional way of distribution of inadequately soluble bazedoxifene acetate drug which is proved from in vivo studies based on the enhanced oral delivery.

scholarly journals HPMC- and PLGA-Based Nanoparticles for the Mucoadhesive Delivery of Sitagliptin: Optimization and In Vivo Evaluation in Rats

Materials ◽  
2019 ◽  
Vol 12 (24) ◽  
pp. 4239 ◽  
Author(s):  
Anroop B. Nair ◽  
Nagaraja Sreeharsha ◽  
Bandar E. Al-Dhubiab ◽  
Jagadeesh G. Hiremath ◽  
Pottathil Shinu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Delivery System ◽  
Oral Therapy ◽  
Ex Vivo ◽  
Narrow Particle Size Distribution ◽  
Drug Content ◽  
Prepared Nanoparticles

Mucoadhesive nanoparticles represent a potential drug delivery strategy to enhance the therapeutic efficacy in oral therapy. This study assessed the prospective of developing HPMC- and PLGA-based nanoparticles using a nanospray drier as a mucoadhesive extended release drug delivery system for sitagliptin and evaluated their potential in an animal model. Nanoparticles were prepared using a Buchi® B-90 nanospray drier. Optimization of particle size was performed using response surface methodology by examining the influence of spray-drying process variables (inlet temperature, feed flow, and polymer concentration) on the particle size. The prepared nanoparticles were characterized for various physicochemical characteristics (yield, drug content, morphology, particle size, thermal, and crystallographic properties) and assessed for drug release, stability, and mucoadhesive efficacy by ex vivo and in vivo studies in rats. A linear model was suggested by the design of the experiments to be the best fit for the generated design and values. The yield was 77 ± 4%, and the drug content was 90.5 ± 3.5%. Prepared nanoparticles showed an average particle size of 448.8 nm, with a narrow particle size distribution, and were wrinkled. Thermal and crystallographic characteristics showed that the drug present in the nanoparticles is in amorphous dispersion. Nanoparticles exhibited a biphasic drug release with an initial rapid release (24.9 ± 2.7% at 30 min) and a prolonged release (98.9 ± 1.8% up to 12 h). The ex vivo mucoadhesive studies confirmed the adherence of nanoparticles in stomach mucosa for a long period. Histopathological assessment showed that the formulation is safe for oral drug delivery. Nanoparticles showed a significantly higher (p < 0.05) amount of sitagliptin retention in the GIT (gastrointestinal tract) as compared to control. The data observed in this study indicate that the prepared mucoadhesive nanoparticles can be an effective alternative delivery system for the oral therapy of sitagliptin.

Quercetin Loaded Nanostructured Lipid Carriers-based Gel for Rheumatoid Arthritis: Formulation, Characterization and in vivo Evaluation

2018 ◽  
Vol 11 (1) ◽  
pp. 3967-3977
Author(s):  
Jayanti P Gokhale ◽  
Sanjay S Surana
Keyword(s):  
Rheumatoid Arthritis ◽  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Blood Cells ◽  
Ex Vivo ◽  
In Vitro Drug Release ◽  
Texture Profile

Present research work describes the development of potential topical treatment containing nanostructured lipid carriers (NLCs) for rheumatoid arthritis (RA). Quercetin (QCT) is a renowned flavonol useful as model drug for carriers. QCT loaded NLCs were prepared and evaluated for particle size distribution, polydispersity index, zeta potential analysis, in vitro drug release study. Ex vivo study was carried out to evaluate the effect of NLCs on cell proliferation (HIG-82 cell line) and inflammation (TNF-α induction in RAW264.7 cells). The QCT-NLCs showed mean particle size of 155.6 ± 1.8 nm and polydispersity index (PDI) was 0.236 ± 0.4, entrapment efficiency of 95.63 ± 0.14 % and zeta potential of -27 ± 1.2 mV. For the ease of application, NLCs were incorporated into the gel base and final formulation was evaluated for rheological study, texture profile, drug release and antiarthritic activity. QCT-NLC gel showed pseudo plastic flow behavior with excellent texture profile parameters. In vitro drug release studies showed that, QCT-NLC gel has more prominent permeation profile as compared with QCT-loaded gel. In vivo activity was carried out using Complete Freund's adjuvant (CFA) induced arthritic model. Evaluation of the severity of rheumatoid arthritis was done by measurements of hind paw volume, arthritis score and haematological parameters such as rheumatoid factor (RF), C-reactive protein (CRP), red blood cells (RBCs), white blood cells (WBCs), erythrocyte sedimentation rate (ESR) and hemoglobin (Hb). Edema and erythema were not observed after administration of QCT-NLC- gel on the rat skin. In conclusion, the results of in vitro and ex vivo studies, QCT-NLC gel appears a viable formulation system for topical delivery of QCT in the treatment of RA.         

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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