scholarly journals A Novel Murine Model for theIn VivoStudy of Transdermal Drug Penetration

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Gábor Erős ◽  
Petra Hartmann ◽  
Szilvia Berkó ◽  
Eszter Csizmazia ◽  
Erzsébet Csányi ◽  
...  
Keyword(s):  
Drug Penetration ◽  
Titanium Plate ◽  
Dorsal Region ◽  
Hairless Mice ◽  
Continuous Increase ◽  
Skin Fold ◽  
Exact Measurement ◽  
Research Goal ◽  
Transdermal Penetration

Enhancement of the transdermal penetration of different active agents is an important research goal. Our aim was to establish a novelin vivoexperimental model which provides a possibility for exact measurement of the quantity of penetrated drug. The experiments were performed on SKH-1 hairless mice. A skin fold in the dorsal region was fixed with two fenestrated titanium plates. A circular wound was made on one side of the skin fold. A metal cylinder with phosphate buffer was fixed into the window of the titanium plate. The concentration of penetrated drug was measured in the buffer. The skin fold was morphologically intact and had a healthy microcirculation. The drug appeared in the acceptor buffer after 30 min, and its concentration exhibited a continuous increase. The presence of ibuprofen was also detected in the plasma. In conclusion, this model allows an exactin vivostudy of drug penetration and absorption.

scholarly journals Liposome percutaneous penetration in vivo

2017 ◽  
Vol 1 ◽  
pp. 239784731772319 ◽  
Author(s):  
A Lymberopoulos ◽  
C Demopoulou ◽  
M Kyriazi ◽  
MS Katsarou ◽  
N Demertzis ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Rhodamine B ◽  
Transdermal Delivery ◽  
Penetration Enhancers ◽  
Percutaneous Penetration ◽  
Hairless Mice ◽  
Liposomal Form ◽  
Multilamellar Vesicles ◽  
Small Unilamellar Vesicles

Objectives: Liposomes are reported as penetration enhancers for dermal and transdermal delivery. However, little is known about their percutaneous penetration and as to at which level they deliver encapsulated drugs. The penetration of multilamellar vesicles (MLVs) and small unilamellar vesicles (SUVs), in comparison to one of their lipid components, was investigated. Methods: Using the fluorescent lipid, Lissamine Rhodamine B-PE (R), as a constituent, MLV and SUV liposomes were prepared, tested, and R, MLV, or SUV were applied in vivo on the back of hairless mice. Absorption of each was evaluated at the levels of stratum corneum, living skin, and blood by fluorometry. Results: Penetration of the lipid R in stratum corneum in the nonliposomal form exceeded that in the liposomal form and only R penetrates the living skin in a statistically significant manner. No statistical significant absorption into blood was observed with either form. Conclusions: Liposomes size did not play an important role in penetration to stratum corneum. The lipid constituent in the nonliposomal form penetrated at higher rates into stratum corneum and living skin. Even though these liposomes entered stratum corneum, they were not significantly absorbed into viable skin or blood.

scholarly journals 5-Aminolevulinic Acid-Based Photodynamic Therapy Pretreatment Mitigates Ultraviolet A-Induced Oxidative Photodamage

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hui Hua ◽  
Jiawei Cheng ◽  
Wenbo Bu ◽  
Juan Liu ◽  
Weiwei Ma ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Epidermal Keratinocytes ◽  
Control Group ◽  
Hacat Cells ◽  
Ultraviolet A ◽  
Hairless Mice ◽  
Human Epidermal Keratinocytes ◽  
Experimental Group

Aim. To determine whether 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is effective in combating ultraviolet A- (UVA-) induced oxidative photodamage of hairless mice skin in vivo and human epidermal keratinocytes in vitro. Methods. In in vitro experiments, the human keratinocyte cell line (HaCaT cells) was divided into two groups: the experimental group was treated with ALA-PDT and the control group was left untreated. Then, the experimental group and the control group of cells were exposed to 10 J/m2 of UVA radiation. ROS, O2− species, and MMP were determined by fluorescence microscopy; p53, OGG1, and XPC were determined by Western blot analysis; apoptosis was determined by flow cytometry; and 8-oxo-dG was determined by immunofluorescence. Moreover, HaCaT cells were also treated with ALA-PDT. Then, SOD1 and SOD2 were examined by Western blot analysis. In in vivo experiments, the dorsal skin of hairless mice was treated with ALA-PDT or saline-PDT, and then, they were exposed to 20 J/m2 UVA light. The compound 8-oxo-dG was detected by immunofluorescence. Conclusion. In human epidermal keratinocytes and hairless mice skin, UVA-induced oxidative damage can be prevented effectively with ALA-PDT pretreatment.

scholarly journals 1577. Particle Characterization of Nebulized Liposomal Amphotericin B and Its Use in the Treatment of Murine Pulmonary Aspergillosis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S576-S576
Author(s):  
Janam J Dave ◽  
Adilene Sandoval ◽  
Jon Olson ◽  
Jill Adler-Moore
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
In Vivo Studies ◽  
Liposomal Amphotericin B ◽  
Drug Penetration ◽  
Particle Characterization ◽  
Pulmonary Aspergillosis ◽  
Fungal Burden

Abstract Background Immunocompromised patients are very susceptible to pulmonary aspergillosis causing 50% mortality with present treatments, indicating a need for improved therapy. To address this, we standardized a nebulization method for effectively delivering liposomal amphotericin B (AmBisome®, AmBi) into lungs of Aspergillus fumigatus-infected mice. Methods AmBi particle characterization was done with a Cascade particle impactor and a Schuco S5000 nebulizer containing 1.33 mg/mL AmBi. For in vivo studies, AmBi was nebulized (neb) into a 12 compartment chamber (one mouse/compartment), following immunosuppression with 28 mg/kg triamcinolone IP (d-3, -1, +1). Mice were challenged d0 with 9 x 106A. fumigatus (ATCC#13073) and 4 hours post-challenge, divided into 5 groups (n = 12/gp): 5 days of 20 min/day neb AmBi (Gp1), 5 days of 10 min/day neb AmBi (Gp2), 20 min/day neb AmBi days 0, 1, 3, 5, 7 (Gp 3), 5 days of intravenous(IV) AmBi 7.5 mg/kg/day (Gp4) and IV PBS (Gp5). Seven mice/gp were monitored for survival to d21 and lungs, livers, kidneys, spleens (5 mice/gp) analyzed for mean amphotericin B µg/g and CFU/g. Results 87% of neb AmBi particles were between 0.43 mm to 3.3 mm allowing for drug penetration into 1°, 2° and terminal bronchi, bronchioles, and alveoli. This resulted in very good protection, with 20 min daily neb treatments (Gp1) giving 100% survival and 10 min daily neb treatments producing 71% survival (Gp2). There were no survivors in the PBS gp (P < 0.02 vs. Gp1 and Gp2). Every other day neb AmBi or daily IV AmBi was less effective (43% survival). In addition, neb AmBi for 20 min (Gp1) yielded significantly lower fungal burden in lungs vs. all other AmBi treatments (P < 0.02). While drug was detected in lungs of mice given 20 min of neb AmBi (2.6 µg/g), there was no drug detected in livers, kidneys or spleens of any mice given neb AmBi. In comparison, with IV AmBi, drug was detected in the lungs (7 µg/g), livers (204 µg/g), kidneys (38 µg/g), and spleens (114 µg/g). Conclusion Daily AmBi nebulization was an effective and potentially less nephrotoxic treatment for murine pulmonary aspergillosis since it achieved significantly lower tissue fungal burden and much better survival vs. daily IV AmBi, without delivering drug to the kidneys. Disclosures All authors: No reported disclosures.

scholarly journals PL3.6 Targeting GSK-3 activity promotes mitotic catastrophe via centrosome destabilisation and enhances the effect of radiotherapy in glioma models

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii4-iii4
Author(s):  
A Bruning-Richardson ◽  
H Sanganee ◽  
S Barry ◽  
D Tams ◽  
T Brend ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Combination Treatment ◽  
Single Agent ◽  
Drug Penetration ◽  
In Vivo Models ◽  
Human Astrocytes ◽  
Normal Human

Abstract BACKGROUND Targeting kinases as regulators of cellular processes that drive cancer progression is a promising approach to improve patient outcome in GBM management. The glycogen synthase kinase 3 (GSK-3) plays a role in cancer progression and is known for its pro-proliferative activity in gliomas. The anti-proliferative and cytotoxic effects of the GSK-3 inhibitor AZD2858 were assessed in relevant in vitro and in vivo glioma models to confirm GSK-3 as a suitable target for improved single agent or combination treatments. MATERIAL AND METHODS The immortalised cell line U251 and the patient derived cell lines GBM1 and GBM4 were used in in vitro studies including MTT, clonogenic survival, live cell imaging, immunofluorescence microscopy and flow cytometry to assess the cytotoxic and anti-proliferative effects of AZD2858. Observed anti-proliferative effects were investigated by microarray technology for the identification of target genes with known roles in cell proliferation. Clinical relevance of targeting GSK-3 with the inhibitor either for single agent or combination treatment strategies was determined by subcutaneous and orthotopic in vivo modelling. Whole mount mass spectroscopy was used to confirm drug penetration in orthotopic tumour models. RESULTS AZD2858 was cytotoxic at low micromolar concentrations and at sub-micromolar concentrations (0.01 - 1.0 μM) induced mitotic defects in all cell lines examined. Prolonged mitosis, centrosome disruption/duplication and cytokinetic failure leading to cell death featured prominently among the cell lines concomitant with an observed S-phase arrest. No cytotoxic or anti-proliferative effect was observed in normal human astrocytes. Analysis of the RNA microarray screen of AZD2858 treated glioma cells revealed the dysregulation of mitosis-associated genes including ASPM and PRC1, encoding proteins with known roles in cytokinesis. The anti-proliferative and cytotoxic effect of AZD2858 was also confirmed in both subcutaneous and orthotopic in vivo models. In addition, combination treatment with AZD2858 enhanced clinically relevant radiation doses leading to reduced tumour volume and improved survival in orthotopic in vivo models. CONCLUSION GSK-3 inhibition with the small molecule inhibitor AZD2858 led to cell death in glioma stem cells preventing normal centrosome function and promoting mitotic failure. Normal human astrocytes were not affected by treatment with the inhibitor at submicromolar concentrations. Drug penetration was observed alongside an enhanced effect of clinical radiotherapy doses in vivo. The reported aberrant centrosomal duplication may be a direct consequence of failed cytokinesis suggesting a role of GSK-3 in regulation of mitosis in glioma. GSK-3 is a promising target for combination treatment with radiation in GBM management and plays a role in mitosis-associated events in glioma biology.

scholarly journals Oral Intake of Collagen Peptide Attenuates Ultraviolet B Irradiation-Induced Skin Dehydration In Vivo by Regulating Hyaluronic Acid Synthesis

2018 ◽  
Vol 19 (11) ◽  
pp. 3551 ◽  
Author(s):  
Min Kang ◽  
Silvia Yumnam ◽  
Sun Kim
Keyword(s):  
Hyaluronic Acid ◽  
Oral Administration ◽  
Protein Expression ◽  
Ultraviolet B ◽  
Skin Hydration ◽  
Skin Barrier Function ◽  
Hairless Mice ◽  
Uvb Irradiation ◽  
Collagen Peptide

Collagen peptide (CP) has beneficial effects on functions of the skin, such as skin barrier function and skin elasticity, in vivo. However, there are few studies investigating the mechanism underlying the potential effects of CP in skin epidermal moisturization after ultraviolet B (UVB) irradiation. In this study, we examined whether orally-administered CP affects the loss of skin hydration induced by UVB irradiation in hairless mice. SKH-1 hairless mice were orally administered CP at two doses (500 and 1000 mg/kg) for nine weeks, and the dorsal skin was exposed to UVB. The potential effects of CP were evaluated by measuring the transepidermal water loss (TEWL), skin hydration, wrinkle formation, and hyaluronic acid expression in the dorsal mice skin. We found that oral administration of CP increased skin hydration and decreased wrinkle formation compared to the UVB-irradiated group. Treatment of CP increased the mRNA and protein expression of hyaluronic acid synthases (HAS-1 and -2) concomitant with an increased hyaluronic acid production in skin tissue. The expression of hyaluronidase (HYAL-1 and 2) mRNA was downregulated in the CP-treated group. In addition, the protein expression of skin-hydrating factors, filaggrin and involucrin, was upregulated via oral administration of CP. In summary, these results show that oral administration of CP increases hyaluronic acid levels, which decreases during UVB photoaging. Therefore, we suggest that CP can be used as a nutricosmetic ingredient with potential effects on UVB-induced skin dehydration and moisture loss in addition to wrinkle formation.

scholarly journals Physical Properties of Nanoparticles That Result in Improved Cancer Targeting

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Randa Zein ◽  
Wissam Sharrouf ◽  
Kim Selting
Keyword(s):  
Adverse Effects ◽  
Physical Properties ◽  
Therapeutic Efficacy ◽  
Biomedical Applications ◽  
Cancer Targeting ◽  
Drug Penetration ◽  
Charge Shape ◽  
Tumor Tissues ◽  
Chemical Attributes

The therapeutic efficacy of drugs is dependent upon the ability of a drug to reach its target, and drug penetration into tumors is limited by abnormal vasculature and high interstitial pressure. Chemotherapy is the most common systemic treatment for cancer but can cause undesirable adverse effects, including toxicity to the bone marrow and gastrointestinal system. Therefore, nanotechnology-based drug delivery systems have been developed to reduce the adverse effects of traditional chemotherapy by enhancing the penetration and selective drug retention in tumor tissues. A thorough knowledge of the physical properties (e.g., size, surface charge, shape, and mechanical strength) and chemical attributes of nanoparticles is crucial to facilitate the application of nanotechnology to biomedical applications. This review provides a summary of how the attributes of nanoparticles can be exploited to improve therapeutic efficacy. An ideal nanoparticle is proposed at the end of this review in order to guide future development of nanoparticles for improved drug targeting in vivo.

scholarly journals Protective Effect of Fermented Soybean Dried Extracts against TPA-Induced Oxidative Stress in Hairless Mice Skin

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Sandra R. Georgetti ◽  
Rúbia Casagrande ◽  
Fabiana T. M. C. Vicentini ◽  
Marcela M. Baracat ◽  
Waldiceu A. Verri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chemical Properties ◽  
Gas Temperature ◽  
Drying Process ◽  
Hairless Mice ◽  
Total Polyphenol ◽  
Biochemical Alterations ◽  
Soybean Extract ◽  
A Minor

This study evaluated the chemical properties (polyphenol and genistein contents) of soybean extracts obtained by biotransformation and dried by spray dryer at different conditions and theirin vivoability to inhibit 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced biochemical alterations in the skin of hairless mice. By comparing the obtained data with that of the well-known active soybean extract Isoflavin beta, we evaluated the influence of the fermentation and drying process in the extracts efficacy. The results demonstrated that inlet gas temperature and adjuvant concentration for the extract drying process have significantly affected the total polyphenol contents and, to a minor degree, the genistein contents. However, the effect of topical stimulus with TPA, an oxidative stress inducer, which caused significant depletion of reduced glutathione (GSH) and catalase, with increased levels of H2O2and lipid peroxidation (MDA) in the skin of hairless mice, was significantly prevented by the soybean extracts treatment. These results indicate that the spray drying processing resulted in a product capable of limiting the oxidative stress with possible therapeutic applicability as an antioxidant in pharmaceutical forms.

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