scholarly journals Characterizing Nanoparticles in Biological Matrices: Tipping Points in Agglomeration State and Cellular Delivery In Vitro

ACS Nano ◽  
2017 ◽  
Vol 11 (12) ◽  
pp. 11986-12000 ◽  
Author(s):  
John W. Wills ◽  
Huw D. Summers ◽  
Nicole Hondow ◽  
Aishwarya Sooresh ◽  
Kenith E. Meissner ◽  
...  
Keyword(s):  
Tipping Points ◽  
Cellular Delivery ◽  
Biological Matrices ◽  
Agglomeration State

Evaluation of in situ gelling chitosan-PEG copolymer for use in the spinal cord

2018 ◽  
Vol 33 (3) ◽  
pp. 435-446 ◽  
Author(s):  
Ashley E Mohrman ◽  
Mahmoud Farrag ◽  
Rachel K Grimm ◽  
Nic D Leipzig
Keyword(s):  
Spinal Cord ◽  
Polyethylene Glycol ◽  
Spinal Cord Injuries ◽  
Similar Response ◽  
Cellular Delivery ◽  
Thiolated Chitosan ◽  
Cord Injury ◽  
In Situ Gelling

The goal of the present work was to characterize a hydrogel material for localized spinal cord delivery. To address spinal cord injuries, an injectable in situ gelling system was tested utilizing a simple, effective, and rapid cross-linking method via Michael addition. Thiolated chitosan material and maleimide-terminated polyethylene glycol material were mixed to form a hydrogel and evaluated in vitro and in vivo. Three distinct thiolated chitosan precursors were made by varying reaction conditions; a modification of chitosan with Traut’s reagent (2-iminothiolane) displayed the most attractive hydrogel properties once mixed with polyethylene glycol. The final hydrogel chosen for animal testing had a swelling ratio (Q) of 57.5 ± 3.4 and elastic modulus of 378 ± 72 Pa. After confirming low cellular toxicity in vitro, the hydrogel was injected into the spinal cord of rats for 1 and 2 weeks to assess host reaction. The rats displayed no overt functional deficits due to injection following initial surgical recovery and throughout the 2-week period after for both the saline-injected sham group and hydrogel-injected group. The saline and hydrogel-injected animals both showed a similar response from ED1+ microglia and GFAP overexpression. No significant differences were found between saline-injected and hydrogel-injected groups for any of the measures studied, but there was a trend toward decreased affected area size from 1 to 2 weeks in both groups. Access to the central nervous system is limited by the blood–brain barrier for noninvasive therapies; further development of the current system for localized drug or cellular delivery has the potential to shape treatments of spinal cord injury.

scholarly journals Toward Biological Pacing by Cellular Delivery of Hcn2/SkM1

2021 ◽  
Vol 11 ◽  
Author(s):  
Anna M. D. Végh ◽  
Arie O. Verkerk ◽  
Lucía Cócera Ortega ◽  
Jianan Wang ◽  
Dirk Geerts ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Patch Clamp ◽  
Computational Modeling ◽  
Sodium Current ◽  
Pacemaker Activity ◽  
Cellular Delivery ◽  
Lentiviral Transduction ◽  
Biological Pacemaker

Electronic pacemakers still face major shortcomings that are largely intrinsic to their hardware-based design. Radical improvements can potentially be generated by gene or cell therapy-based biological pacemakers. Our previous work identified adenoviral gene transfer of Hcn2 and SkM1, encoding a “funny current” and skeletal fast sodium current, respectively, as a potent combination to induce short-term biological pacing in dogs with atrioventricular block. To achieve long-term biological pacemaker activity, alternative delivery platforms need to be explored and optimized. The aim of the present study was therefore to investigate the functional delivery of Hcn2/SkM1 via human cardiomyocyte progenitor cells (CPCs). Nucleofection of Hcn2 and SkM1 in CPCs was optimized and gene transfer was determined for Hcn2 and SkM1 in vitro. The modified CPCs were analyzed using patch-clamp for validation and characterization of functional transgene expression. In addition, biophysical properties of Hcn2 and SkM1 were further investigated in lentivirally transduced CPCs by patch-clamp analysis. To compare both modification methods in vivo, CPCs were nucleofected or lentivirally transduced with GFP and injected in the left ventricle of male NOD-SCID mice. After 1 week, hearts were collected and analyzed for GFP expression and cell engraftment. Subsequent functional studies were carried out by computational modeling. Both nucleofection and lentiviral transduction of CPCs resulted in functional gene transfer of Hcn2 and SkM1 channels. However, lentiviral transduction was more efficient than nucleofection-mediated gene transfer and the virally transduced cells survived better in vivo. These data support future use of lentiviral transduction over nucleofection, concerning CPC-based cardiac gene delivery. Detailed patch-clamp studies revealed Hcn2 and Skm1 current kinetics within the range of previously reported values of other cell systems. Finally, computational modeling indicated that CPC-mediated delivery of Hcn2/SkM1 can generate stable pacemaker function in human ventricular myocytes. These modeling studies further illustrated that SkM1 plays an essential role in the final stage of diastolic depolarization, thereby enhancing biological pacemaker functioning delivered by Hcn2. Altogether these studies support further development of CPC-mediated delivery of Hcn2/SkM1 and functional testing in bradycardia models.

HPLC–UV method for temozolomide determination in complex biological matrices: Application for in vitro , ex vivo and in vivo studies

2019 ◽  
Vol 33 (10) ◽  
Author(s):  
Luana R. Michels ◽  
Flávia N.S. Fachel ◽  
Juliana H. Azambuja ◽  
Nicolly E. Gelsleichter ◽  
Elizandra Braganhol ◽  
...  
Keyword(s):  
Ex Vivo ◽  
In Vivo Studies ◽  
Biological Matrices

Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid).

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Cell Lines ◽  
Malic Acid ◽  
Multi Drug Resistance ◽  
Cellular Delivery ◽  
Major Drawback ◽  
Carcinoma Cell Lines ◽  
Primary Glioma ◽  
Breast Carcinoma Cell Lines ◽  
Reduced Toxicity

Doxorubicin (DOX) is currently used in cancer chemotherapy to treat manytumors and shows improved delivery, reduced toxicity and higher treatment efficacy whenbeing part of nanoscale delivery systems. However, a major drawback remains its toxicityto healthy tissue and the development of multi-drug resistance during prolonged treatment.This is why in our work we aimed to improve DOX delivery and reduce the toxicity bychemical conjugation with a new nanoplatform based on polymalic acid. For delivery intorecipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage alongwith polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenicnanoconjugate platform: poly(β-L-malic acid) (PMLA). DOX-nanoconjugates were foundstable under physiological conditions and shown to successfully inhibit in vitro cancercell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 andMDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.

scholarly journals Anticancer Activity of Ferulic Acid-Inorganic Nanohybrids Synthesized via Two Different Hybridization Routes, Reconstruction and Exfoliation-Reassembly

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hyoung-Jun Kim ◽  
Kitae Ryu ◽  
Joo-Hee Kang ◽  
Ae-Jin Choi ◽  
Tae-il Kim ◽  
...  
Keyword(s):  
Particle Size ◽  
Ferulic Acid ◽  
Anticancer Activity ◽  
Layered Double Hydroxide ◽  
Culture Media ◽  
Average Particle Size ◽  
Average Particle ◽  
Cellular Delivery ◽  
Double Hydroxide

We have successfully prepared nanohybrids of biofunctional ferulic acid and layered double hydroxide nanomaterials through reconstruction and exfoliation-reassembly routes. From X-ray diffraction and infrared spectroscopy, both nanohybrids were determined to incorporate ferulic acid molecules in anionic form. Micrsocopic results showed that the nanohybrids had average particle size of 150 nm with plate-like morphology. As the two nanohybridization routes involved crystal disorder and random stacking of layers, the nanohybrids showed slight alteration inz-axis crystallinity and particle size. The zeta potential values of pristine and nanohybrids in deionized water were determined to be positive, while those in cell culture media shifted to negative values. According to thein vitroanticancer activity test on human cervical cancer HeLa cells, it was revealed that nanohybrids showed twice anticancer activity compared with ferulic acid itself. Therefore we could conclude that the nanohybrids of ferulic acid and layered double hydroxide had cellular delivery property of intercalated molecules on cancer cell lines.

Tensional forces in fibrillar extracellular matrices control directional capillary sprouting

1999 ◽  
Vol 112 (19) ◽  
pp. 3249-3258 ◽  
Author(s):  
T. Korff ◽  
H.G. Augustin
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Three Dimensional ◽  
Type I ◽  
Cellular Delivery ◽  
Form Complex ◽  
Cell Spheroid ◽  
In Vitro Angiogenesis

During angiogenesis, anastomosing capillary sprouts align to form complex three-dimensional networks of new blood vessels. Using an endothelial cell spheroid model that was developed to study endothelial cell differentiation processes, we have devised a novel collagen gel-based three-dimensional in vitro angiogenesis assay. In this assay, cell number-defined, gel-embedded endothelial cell spheroids act as a cellular delivery device, which serves as a focal starting point for the sprouting of lumenized capillary-like structures that can be induced to form complex anastomosing networks. Formation of capillary anastomoses is associated with tensional remodeling of the collagen matrix and directional sprouting of outgrowing capillaries towards each other. To analyze whether directional sprouting is dependent on cytokine gradients or on endothelial cell-derived tractional forces transduced through the extracellular matrix, we designed a matrix tension generator that enables the application of defined tensional forces on the extracellular matrix. Using this matrix tension generator, causal evidence is presented that tensional forces on a fibrillar extracellular matrix such as type I collagen, but not fibrin, are sufficient to guide directional outgrowth of endothelial cells. RGD peptides but not control RAD peptides disrupted the integrity of sprouting capillary-like structures and induced detachment of outgrowing endothelial cells cultured on top of collagen gels, but did not inhibit primary outgrowth of endothelial cells. The data establish the endothelial cell spheroid-based three-dimensional angiogenesis technique as a standardized, highly reproducible quantitative assay for in vitro angiogenesis studies and demonstrate that integrin-dependent matrix tensional forces control directional capillary sprouting and network formation.

RELATIVE ANTIGEN-SPECIFIC SUPPRESSION IN VITRO OF ALLORESPONDING HUMAN LEUKOCYTES BY CELLULAR DELIVERY OF CYCLOSPORINE

1987 ◽  
Vol 44 (1) ◽  
pp. 119-122 ◽  
Author(s):  
JEFFREY E. CHRISTIAANSEN ◽  
FLORENCE SCHMID-FORMBY ◽  
CHARLES M. PETERSON
Keyword(s):  
Cellular Delivery ◽  
Human Leukocytes ◽  
Specific Suppression

scholarly journals Agglomeration State of Titanium-Dioxide (TiO2) Nanomaterials Influences the Dose Deposition and Cytotoxic Responses in Human Bronchial Epithelial Cells at the Air-Liquid Interface

Nanomaterials ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3226
Author(s):  
Sivakumar Murugadoss ◽  
Sonja Mülhopt ◽  
Silvia Diabaté ◽  
Manosij Ghosh ◽  
Hanns-Rudolf Paur ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Liquid Interface ◽  
Glutathione Depletion ◽  
In Vivo Studies ◽  
Nano Tio2 ◽  
Bronchial Epithelial ◽  
Agglomeration State ◽  
Dose Deposition ◽  
Air Liquid Interface

Extensive production and use of nanomaterials (NMs), such as titanium dioxide (TiO2), raises concern regarding their potential adverse effects to humans. While considerable efforts have been made to assess the safety of TiO2 NMs using in vitro and in vivo studies, results obtained to date are unreliable, possibly due to the dynamic agglomeration behavior of TiO2 NMs. Moreover, agglomerates are of prime importance in occupational exposure scenarios, but their toxicological relevance remains poorly understood. Therefore, the aim of this study was to investigate the potential pulmonary effects induced by TiO2 agglomerates of different sizes at the air–liquid interface (ALI), which is more realistic in terms of inhalation exposure, and compare it to results previously obtained under submerged conditions. A nano-TiO2 (17 nm) and a non-nano TiO2 (117 nm) was selected for this study. Stable stock dispersions of small agglomerates and their respective larger counterparts of each TiO2 particles were prepared, and human bronchial epithelial (HBE) cells were exposed to different doses of aerosolized TiO2 agglomerates at the ALI. At the end of 4h exposure, cytotoxicity, glutathione depletion, and DNA damage were evaluated. Our results indicate that dose deposition and the toxic potential in HBE cells are influenced by agglomeration and exposure via the ALI induces different cellular responses than in submerged systems. We conclude that the agglomeration state is crucial in the assessment of pulmonary effects of NMs.

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