Tae-Kyung Ryu

Bone-targeted delivery of nanodiamond-based drug carriers conjugated with alendronate for potential osteoporosis treatment

This paper describes the design of alendronate-conjugated nanodiamonds (Alen-NDs) and evaluation of their feasibility for bone-targeted delivery. Alen-NDs exhibited a high affinity to hydroxyapatite (HAp, the mineral component of bone) due to the presence of Alen. Unlike NDs (without Alen), Alen-NDs were preferentially taken up by MC3T3-E1 osteoblast-like cells, compared to NIH3T3 and HepG2 cells, suggesting their cellular specificity. In addition, NDs itself increased ALP activity of MC3T3-E1 cells, compared to control group (osteogenic medium) and Alen-NDs exhibited more enhanced ALP activity. In addition, an in vivo study revealed that Alen-NDs effectively accumulated in bone tissues after intravenous tail vein injection. These results confirm the superior properties of Alen-NDs with advantages of high HAp affinity, specific uptake for MC3T3-E1 cells, positive synergistic effect for ALP activity, and in vivo bone targeting ability. The Alen-NDs can potentially be employed for osteoporosis treatment by delivering both NDs and Alen to bone tissue.

Cellular Uptake Behavior of Doxorubicin‐Conjugated Nanodiamond Clusters for Efficient Cancer Therapy

This paper describes the design and fabrication of doxorubicin (Dox)-conjugated nanodiamond (ND) clusters with controlled sizes and cellular uptake behaviors of free Dox and Dox-conjugated ND clusters. The ND clusters with an average size of 45.84 nm exhibited a higher amount of cellular uptake as compared to the ND clusters with larger sizes. The amount of Dox taken up as free Dox increased initially and then decreased over time. In contrast, the amount of Dox taken up as Dox-ND clusters continuously increased and reached a plateau, resulting in high ablation efficiency. At the same Dox concentration, the cell viabilities after treatment with free Dox and Dox-ND clusters were 26.38 and 5.31%, respectively. The Dox-ND clusters potentially could be employed as efficient drug carriers for efficient cancer therapy.

Alendronate-modified hydroxyapatite nanoparticles for bone-specific dual delivery of drug and bone mineral

Alendronate (Alen)-modified hydroxyapatite (HAp) nanoparticles with multilayers of poly(allylamine) (PAA) and alginate (ALG) were fabricated for bone-specific dual delivery of drug and mineral. Negatively charged HAp nanoparticles were coated with three layers of PAA and ALG using a layer-by-layer (LbL) method and then conjugated with Alen at the outmost layer of the LbL-coated HAp nanoparticles via carbodiimide chemistry. Alen-modified HAp nanoparticles had a spherical morphology and an average size of 61.5 nm. The superior adsorption property of the Alen-modified HAp nanoparticles was quantitatively confirmed using tricalcium phosphate disks as a bone model, compared to HAp nanoparticles. Cell culture assays revealed a higher proliferation rate and alkaline phosphatase activity of osteoblasts treated with the Alen-modified HAp nanoparticles.

Fabrication of poly(L-lactide) porous beads coated with hydroxyapatite using a simple fluidic device for tissue engineering

Joo Hwan Kim, Tae-Kyung Ryu, Seung-Kwan Moon, Ji-Seon Lee, Kyeongsoon Park, Sung Eun Kim*3, and Sung-Wook Choi* 1Department of Biotechnology, The Catholic University of Korea, Bucheon 420-743, Korea Division of Bioimaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Korea 3Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Medical College, Seoul 152-703, Korea

Sustained release of antibiotics from uniform poly (ε-caprolactone) microspheres prepared by a simple fluidic device with a tapered glass capillary

Uniform poly(ε-caprolactone) microspheres containing a variety of water-soluble antibiotics, such as tobramycin, vancomycin, and gentamicin, were prepared by a simple fluidic device with a pristine or tapered glass capillary. Each type of antibiotic was dispersed in an organic solvent by ball-milling prior to microsphere preparation. The poly(ε-caprolactone) organic solution containing the powder of each antibiotic was introduced as the discontinuous phase into the fluidic device, where an aqueous phase containing surfactant served as the continuous phase. The poly(ε-caprolactone) microspheres were obtained after solvent evaporation. A tapered glass capillary was tested to produce poly(ε-caprolactone) microspheres, leading to the size reduction of the microspheres from 47.46 ± 0.72 to 25.49 ± 1.05 µm without destroying size uniformity. This size range should be suitable for parenteral injection into the human body. The release analysis revealed that gentamicin and vancomycin were released from the poly(ε-caprolactone) microspheres up to approximately 2 months in a more sustained manner than tobramycin, which is due to the solubility difference in the antibiotics in water. The antimicrobial activities of each type of antibiotic released from the poly(ε-caprolactone) microspheres were evaluated using Staphylococcus aureus and Escherichia coli.

Targeted Tumor Therapy Based on Nanodiamonds Decorated with Doxorubicin and Folic Acid.

The fabrication of nanodiamond (ND)-based drug carriers for tumor-targeted drug delivery is described. The ND clusters with an average size of 52.84 nm are fabricated using a simple fluidic device combined with a precipitation method and then conjugated with folic acid (FA) and doxorubicin (Dox) via carbodiimide chemistry to obtain FA/Dox-modified ND (FA/Dox-ND) clusters. Cell culture experiments revealed that KB (folate receptor-positive) cells are preferentially ablated by FA/Dox-ND clusters compared to A549 (folate receptor-negative) cells. In vivo results revealed that FA/Dox-ND clusters are specifically accumulated in tumor tissues after intravenous injection into tumor-bearing mice, effectively reducing the volume of tumor. Based on these results, this study suggests that FA/Dox-ND clusters can be a good candidate as tumor-targeted nanovehicles for delivery of antitumor drug.

Photodynamic and photothermal tumor therapy using phase-change material nanoparticles containing chlorin e6 and nanodiamonds

Abstract This paper describes the fabrication and evaluation of phase‐change material (PCM) nanoparticles containing chlorin e6 (Ce6) and nanodiamonds (NDs) for photodynamic and photothermal approaches for tumor therapy, respectively. The temperature of the PCM nanoparticles containing NDs (ND/PCM, 0.5 mg/mL in water) is increased to 45 °C during laser exposure for 5 min. The singlet oxygen generation intensity of PCM nanoparticles containing Ce6 and NDs (Ce6/ND/PCM) is gradually increased with respect to the laser exposure time. Also, the release of Ce6 from Ce6/ND/PCM can be controlled in an on‐and‐off manner using laser. Cell ablation tests reveal that Ce6/ND/PCM greatly ablates KB cells upon laser exposure, which is attributed to both the temperature increase in the media and singlet oxygen generation by the released Ce6. In an animal model, tumor volume is notably reduced over time after the intratumoral injection of Ce6/ND/PCM and subsequent laser exposure with a higher efficiency compared to ND/PCM. The Ce6/ND/PCM can be a promising nanomedicine for tumor therapy. Graphical abstract Figure. No Caption available.

Fabrication of blue-fluorescent nanodiamonds modified with alkyl isocyanate for cellular bioimaging

This paper describes the fabrication of water-dispersible nanodiamond (ND) clusters with blue fluorescence for cellular bioimaging. Poly(ethylene glycol) carboxyl methyl acid (mPEG-COOH) and alkyl isocyanates with different chain lengths were conjugated onto the surface of the ND clusters for water dispersibility and fluorescence via carbodiimide chemistry. The relative fluorescence intensity was increased with the increases in the chain length of alkyl isocyanate and also their conjugated concentration. The ND clusters (average size of 37.6 nm and zeta potential of 26.6 mV) with mPEG-COOH and octadecyl isocyanate (ODI) emitted relatively higher blue fluorescence intensity under excitation at 350 nm as well as favorable water dispersibility. After cellular uptake of the ND clusters, blue fluorescence inside the cells was confirmed by confocal laser scanning microscopy. The ND clusters conjugated with mPEG-COOH and ODI can potentially be used for cellular bioimaging.

Biodegradable uniform microspheres based on solid-in-oil-in-water emulsion for drug delivery: A comparison of homogenization and fluidic device

Based on solid-in-oil-in-water emulsification, we fabricated biodegradable poly(ϵ-caprolactone) microspheres containing gentamicin using conventional homogenization and a fluidic device. The feasibility of the poly(ϵ-caprolactone) microspheres as drug carriers was evaluated in terms of encapsulation efficiency, release behavior of gentamicin, and antimicrobial activity. The poly(ϵ-caprolactone) microspheres prepared using a fluidic device (fluidic device microspheres) had a uniform diameter and a smooth surface, whereas the poly(ϵ-caprolactone) microspheres prepared using conventional homogenization (conventional homogenization microspheres) exhibited polydisperse and a porous structure. At 0.3 wt% of gentamicin concentration, the encapsulation efficiencies of the conventional homogenization and fluidic device microspheres were 39.5% and 72.0%, respectively. In addition, a significant amount of gentamicin was only released initially from the conventional homogenization microspheres, whereas the fluidic device microspheres released gentamicin in a sustained manner for 28 days. These results confirmed the superior performances of the uniform fluidic device microspheres for drug delivery system. We further proposed a model for microsphere formation to explain the difference in performance of the conventional homogenization and fluidic device microspheres.