scholarly journals Photodynamic Therapy of Ovarian Carcinoma Cells with Curcumin-Loaded Biodegradable Polymeric Nanoparticles

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 282 ◽  
Author(s):  
Lili Duse ◽  
Michael Rene Agel ◽  
Shashank Reddy Pinnapireddy ◽  
Jens Schäfer ◽  
Mohammed A. Selo ◽  
...  

Accumulation of photosensitisers in photodynamic therapy in healthy tissues is often the cause of unwanted side effects. Using nanoparticles, improved bioavailability and site-specific drug uptake can be achieved. In this study, curcumin, a natural product with anticancer properties, albeit with poor aqueous solubility, was encapsulated in biodegradable polymeric poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CUR-NP). Dynamic light scattering, laser Doppler anemometry and atomic force microscopy were used to characterise the formulations. Using haemolysis, serum stability and activated partial thromboplastin time tests, the biocompatibility of CUR-NP was assessed. Particle uptake and accumulation were determined by confocal laser scanning microscopy. Therapeutic efficacy of the formulation was tested in SK-OV-3 human ovarian adenocarcinoma cells post low level LED irradiation by determining the generation of reactive oxygen species and cytotoxicity. Pharmacologic inhibitors of cellular uptake pathways were used to identify the particle uptake mechanism. CUR-NP exhibited better physicochemical properties such as stability in the presence of light and improved serum stability compared to free curcumin. In addition, the novel nanoformulation facilitated the use of higher amounts of curcumin and showed strong apoptotic effects on tumour cells.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1243
Author(s):  
Jennifer Lehmann ◽  
Michael R. Agel ◽  
Konrad H. Engelhardt ◽  
Shashank R. Pinnapireddy ◽  
Sabine Agel ◽  
...  

Lung cancer is one of the most common causes for a high number of cancer related mortalities worldwide. Therefore, it is important to improve the therapy by finding new targets and developing convenient therapies. One of these novel non-invasive strategies is the combination of pulmonary delivered tetraether liposomes and photodynamic therapy. In this study, liposomal model formulations containing the photosensitiser curcumin were nebulised via two different technologies, vibrating-mesh nebulisation and air-jet nebulisation, and compared with each other. Particle size and ζ-potential of the liposomes were investigated using dynamic light scattering and laser Doppler anemometry, respectively. Furthermore, atomic force microscopy and transmission electron microscopy were used to determine the morphological characteristics. Using a twin glass impinger, suitable aerodynamic properties were observed, with the fine particle fraction of the aerosols being ≤62.7 ± 1.6%. In vitro irradiation experiments on lung carcinoma cells (A549) revealed an excellent cytotoxic response of the nebulised liposomes in which the stabilisation of the lipid bilayer was the determining factor. Internalisation of nebulised curcumin-loaded liposomes was visualised utilising confocal laser scanning microscopy. Based on these results, the pulmonary application of curcumin-loaded tetraether liposomes can be considered as a promising approach for the photodynamic therapy against lung cancer.


2019 ◽  
Author(s):  
Emma Björk ◽  
Bernhard Baumann ◽  
Florian Hausladen ◽  
Rainer Wittig ◽  
mika lindén

Spatially and temporally controlled drug delivery is important for implant and tissue engineering applications, as the efficacy and bioavailability of the drug can be enhanced, and can also allow for drugging stem cells at different stages of development. Long-term drug delivery over weeks to months is however difficult to achieve, and coating of 3D surfaces or creating patterned surfaces is a challenge using coating techniques like spin- and dip-coating. In this study, mesoporous films consisting of SBA-15 particles grown onto silicon wafers using wet processing were evaluated as a scaffold for drug delivery. Films with various particle sizes (100 – 900 nm) and hence thicknesses were grown onto OTS-functionalized silicon wafers using a direct growth method. Precise patterning of the areas for film growth could be obtained by local removal of the OTS functionalization through laser ablation. The films were incubated with the model drug DiO, and murine myoblast cells (C2C12 cells) were seeded onto films with different particle sizes. Confocal laser scanning microscopy (CLSM) was used to study the cell growth, and a vinculin-mediated adherence of C2C12 cells on all films was verified. The successful loading of DiO into the films was confirmed by UV-vis and CLSM. It was observed that the drugs did not desorb from the particles during 24 hours in cell culture. During adherent growth on the films for 4 h, small amounts of DiO and separate particles were observed inside single cells. After 24 h, a larger number of particles and a strong DiO signal were recorded in the cells, indicating a particle mediated drug uptake. A substantial amount of DiO loaded particles were however attached on the substrate after 24 making the films attractive as a long-term reservoir for drugs on e.g. medical implants.<br>


Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7342
Author(s):  
Wei Liu ◽  
Xingqun Ma ◽  
Yingying Jin ◽  
Jie Zhang ◽  
Yang Li ◽  
...  

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.


1998 ◽  
Vol 550 ◽  
Author(s):  
Chris Thanos ◽  
Maryellen Sandor ◽  
Yong Jong ◽  
Jules Jacob ◽  
Kay-Pong Yip ◽  
...  

AbstractParticle uptake into intestinal tissue has seen increasing attention due to its implications in drug delivery. We attempted to observe a delivery system in vivo and examine uptake in different species. Microspheres were fabricated from polymers including polyanhydrides and delivered to an isolated loop of intestine in several species. The microspheres contained a dye either conjugated to a protein or incorporated freely and were used to qualitatively detect and locate the spheres in the villi of the length of the small intestine. Microspheres were dispersed, sized by a Coulter particle size analyzer, and characterized by confocal and cross-polarized light microscopy, FTIR and SEM. Coulter analysis revealed microspheres to be generally less than 5 microns in diameter. SEM typically showed homogeneous morphology among groups of microspheres. In vivo uptake experiments were performed in rodents, pigs, and ruminants using various microsphere formulations. Microspheres were delivered into the proximal end of the jejunum of anesthetized animals and allowed adequate transit time to be taken up. Animals were euthanized at various time points for explantation of tissue and sampling of blood. Excised samples were embedded inq polyvinyl alcohol, frozen, and cut into sections ranging between 7 and 14 μm in thickness. Our method of incorporating dyes allowed for simultaneous visualization by visible light microscopy and confocal laser scanning microscopy. Two-fluorochrome fluorescence of the microspheres and optical sectioning confirmed the presence of microspheres within intestinal tissue. The amount of uptake depended on the animal model, the duration of the experiment, and the composition of the microsphere. An assay for either the fluorescent dye, the protein attached to it, or the polymer encapsulating it may enable us to determine intracellular concentrations of mierospheres for the quantification of uptake.


2019 ◽  
Author(s):  
Emma Björk ◽  
Bernhard Baumann ◽  
Florian Hausladen ◽  
Rainer Wittig ◽  
mika lindén

Spatially and temporally controlled drug delivery is important for implant and tissue engineering applications, as the efficacy and bioavailability of the drug can be enhanced, and can also allow for drugging stem cells at different stages of development. Long-term drug delivery over weeks to months is however difficult to achieve, and coating of 3D surfaces or creating patterned surfaces is a challenge using coating techniques like spin- and dip-coating. In this study, mesoporous films consisting of SBA-15 particles grown onto silicon wafers using wet processing were evaluated as a scaffold for drug delivery. Films with various particle sizes (100 – 900 nm) and hence thicknesses were grown onto OTS-functionalized silicon wafers using a direct growth method. Precise patterning of the areas for film growth could be obtained by local removal of the OTS functionalization through laser ablation. The films were incubated with the model drug DiO, and murine myoblast cells (C2C12 cells) were seeded onto films with different particle sizes. Confocal laser scanning microscopy (CLSM) was used to study the cell growth, and a vinculin-mediated adherence of C2C12 cells on all films was verified. The successful loading of DiO into the films was confirmed by UV-vis and CLSM. It was observed that the drugs did not desorb from the particles during 24 hours in cell culture. During adherent growth on the films for 4 h, small amounts of DiO and separate particles were observed inside single cells. After 24 h, a larger number of particles and a strong DiO signal were recorded in the cells, indicating a particle mediated drug uptake. A substantial amount of DiO loaded particles were however attached on the substrate after 24 making the films attractive as a long-term reservoir for drugs on e.g. medical implants.<br>


2020 ◽  
Vol 47 (1) ◽  
pp. 70-77
Author(s):  
Choa Park ◽  
Howon Park ◽  
Juhyun Lee ◽  
Hyunwoo Seo ◽  
Siyoung Lee

The present study is aimed to assess the effect of antimicrobial photodynamic therapy (aPDT) on <i>Streptococcus mutans</i> biofilm through teeth whitening light emitting diode (LED).<br/>Planktonic and dynamic biofilm state cultures of <i>S. mutans</i> were used. Erythrosine 20 μM/L was used as the photosensitizer. Irradiation was performed by exposing cultures to clinic and homecare whitening LEDs for 15 minutes. The viability was measured through Colony Forming Unit counts and confocal laser scanning microscopy.<br/>aPDT using whitening LEDs and erythrosine significantly decreased the CFU count of <i>S. mutans</i> compared to that in the control group. Dynamic biofilm group showed more resistant features to aPDT compared with planktonic state. Clinic and homecare whitening LED device showed similar antimicrobial effect.<br/>The whitening LED, which could irradiate the entire oral arch, showed a significant photodynamic effect on cariogenic <i>S. mutans</i> biofilm. aPDT mediated by erythrosine and LEDs used for teeth whitening exhibited promising antimicrobial activity.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2099
Author(s):  
Eva Susnik ◽  
Patricia Taladriz-Blanco ◽  
Barbara Drasler ◽  
Sandor Balog ◽  
Alke Petri-Fink ◽  
...  

Silica nanoparticles (NPs) are widely used in various industrial and biomedical applications. Little is known about the cellular uptake of co-exposed silica particles, as can be expected in our daily life. In addition, an inflamed microenvironment might affect a NP’s uptake and a cell’s physiological response. Herein, prestimulated mouse J774A.1 macrophages with bacterial lipopolysaccharide were post-exposed to micron- and nanosized silica particles, either alone or together, i.e., simultaneously or sequentially, for different time points. The results indicated a morphological change and increased expression of tumor necrosis factor alpha in lipopolysaccharide prestimulated cells, suggesting a M1-polarization phenotype. Confocal laser scanning microscopy revealed the intracellular accumulation and uptake of both particle types for all exposure conditions. A flow cytometry analysis showed an increased particle uptake in lipopolysaccharide prestimulated macrophages. However, no differences were observed in particle uptakes between single- and co-exposure conditions. We did not observe any colocalization between the two silica (SiO2) particles. However, there was a positive colocalization between lysosomes and nanosized silica but only a few colocalized events with micro-sized silica particles. This suggests differential intracellular localizations of silica particles in macrophages and a possible activation of distinct endocytic pathways. The results demonstrate that the cellular uptake of NPs is modulated in inflamed macrophages but not in the presence of micron-sized particles.


Nanomedicine ◽  
2019 ◽  
Vol 14 (21) ◽  
pp. 2853-2871 ◽  
Author(s):  
Chen Yang ◽  
Yixiang Wang ◽  
Yike Xie ◽  
Guangyu Liu ◽  
Yi Lu ◽  
...  

Aim: Oat protein-shellac nanoparticles (NPs) were developed as a delivery system for resveratrol to improve bioavailability. Materials & methods: The NPs were prepared from w/w emulsion followed by cold-gelation. In vitro release and cell uptake mechanism of NPs were estimated by HPLC and confocal laser scanning microscopy. In vivo bioavailability and hepatoprotective activity of encapsulated resveratrol were studied using rat models. Results & conclusion: NPs (90–300 nm) protected resveratrol in gastric fluid, while allowing controlled release into small intestine in vitro. The optimized NPs showed improvement in resveratrol cell uptake and transport when compared with free resveratrol. NP-100S increased resveratrol bioavailability up to 72.4%, and the absorbed resveratrol effectively prevented CCl4-induced hepatotoxicity by attenuating oxidative stress.


2020 ◽  
Vol 47 (2) ◽  
pp. 120-127
Author(s):  
Junhee Kho ◽  
Howon Park ◽  
Juhyun Lee ◽  
Hyunwoo Seo ◽  
Siyoung Lee

The aim of this study was to evaluate the antimicrobial effect of photodynamic therapy (PDT) using plaque disclosing agent, 10 - 20 mM erythrosine, as a photosensitizer.<br/>Multispecies cariogenic biofilms containing Streptococcus mutans , Lactobacillus casei and Candida albicans were formed on hydroxyapatite disc. 20 μM, 10 mM and 20 mM erythrosine were applied as a photosensitizer for 3 minutes, and then light-emitting diode (LED) irradiated for 24 seconds. Colony-forming unit (CFU) were measured and biofilms were observed using confocal laser scanning microscopy (CLSM). CFU were significantly decreased in the PDT groups using 10 - 20 mM erythrosine (10 mM, 20mM) and the results were also confirmed by CLSM.<br/>This study confirms the high antimicrobial effect of photodynamic therapy using plaque disclosing agent as a photosensitizer.


Sign in / Sign up

Export Citation Format

Share Document