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Methodologies for synthesizing drug-loaded alginate nanocapsules were optimized and indomethacin and phloroglucinol loading capacities were studied. Their biological effects were studied for ameliorating fine dust (FD) induced detrimental effects in keratinocytes. The 1 % alginate to oil phase ratio of 1:20 was the optimal parameter for water in oil emulsification. The oil phase was optimized to contain sunflower oil: span 80 ratios of 17:3. Nanocapsule drug encapsulation efficiencies were 36.91 ± 5.56 and 32.41 ± 4.05 % respectively for phloroglucinol (EG2P) and indomethacin (EG2I) while the loading capacities were 25.28 ± 3.36 and 23.15 ± 2.84 %. Dried nanocapsules indicated a 40-140 nm diameter range while their hydrodynamic diameter was 989.69 nm at pH 7.0. Nanocapsules swelling was pH-dependent and in releasing media of pH values 4.5, 7.4, and 8.5, the drug release indicated a complex mechanism of swelling, diffusion, and erosion while at pH 2.0 the drug release followed the non-Fickian release. EG2P and EG2I treatment dose-dependently lowered FD-induced intracellular ROS production, apoptosis and inflammatory responses mediated through the NF-κB pathway in FD stimulated HaCaT keratinocytes and reduced epidermal barrier degradation. Further research could investigate the use of this technique in formulating cosmeceuticals containing drug-loaded alginate nanocapsules for achieving controlled release.

The main objective of this study was to prepare functional allopurinol (ALP) incorporated biomaterials using mungbean starch, polyvinyl alcohol, melanin (MEL), and plasticizers. Prepared biomaterials were characterized by FE-SEM and FT-IR analysis. Photothermal conversion efficiencies and ALP release properties of biomaterials were evaluated with NIR laser irradiation. When biomaterials were irradiated with the NIR laser, temperatures increase of MEL-added biomaterials were higher than those of MEL-non-added biomaterials. After NIR laser irradiation, ALP release rates of MEL-added biomaterials were 1.62 times faster than those of MEL-non-added biomaterials. In addition, ALP release using an artificial skin was increased by NIR laser irradiation. ALP release from biomaterials followed Fickian diffusion mechanism, while ALP release using an artificial skin followed a non-Fickian diffusion mechanism. Xanthine oxidase inhibitory (%) for MEL-added biomaterials with/without the addition of GL and XL were 47.5%, 61.7%, and 65.1%, respectively.

In this study, we chemically modified poly(L-lactic acid) (PLLA) with functional amine groups and fabricated a PLLA membrane crosslinked with genipin as a biomembrane for inducing guided bone regeneration (GBR). The mechanical strength of the PLLA-amine membrane was improved by crosslinking with genipin compared to pure PLLA membrane. The surface of the PLLA-amine membrane crosslinked with genipin had many more uniform pores. Attachment and proliferation of MC3T3-E1 cells were increased and improved on the PLLA-amine membrane crosslinked with genipin. In an in vitro osteogenesis study, MC3T3-E1 cells on the PLLA membrane showed higher alkaline phosphatase (ALP) activity and calcification ability evaluated by alizarin red S staining than those on the pure PLLA membrane. When a skull defect hole of a rat was covered with the PLLA-amine membrane crosslinked with genipin, vigorous new bone regeneration determined by computed tomography at 8 weeks post operation was superior to that when the skull defect was covered with the pure PLLA membrane. Taken together, these results demonstrate that the PLLA-amine membrane crosslinked with genipin has a promising therapeutic application to GBR as a barrier membrane for covering the defect site.

Stimuli-responsive drug delivery systems can respond to specific external stimuli, resulting in improved treatment outcomes and reduced side effects from their controllable site-specific release ability. The aim of this study was to develop a thermo-responsive bubble-generating drug release platform by near-infrared (NIR) laser irradiation using melanin-perfluorohexane-methotrexate-polylactic acid (Mel @PFH@MTX-PLA) nanoparticles. Mel@PFH@MTX-PLA nanoparticles were successfully prepared without precipitation or aggregation. By adjusting the amount of perfluorohexane (PFH), a size of Mel@PFH@MTX-PLA nanoparticles with optimal conditions was about 52.75 ± 1.41 nm. Due to the photothermal conversion properties of melanin, the temperature of the Mel@PFH@MTX-PLA nanoparticles was increased to about 59.2 °C after 7 min of 808 nm NIR laser irradiation at a power density of 1.5 W/cm2. The NIR laser-induced temperature increase triggered additional drug release and caused the phase transition of PFH, resulting in dramatic bubble generation. The resultant Mel@PFH@MTX-PLA nanoparticles can be utilized in biomedical applications as promising carriers for localized and controlled drug delivery.

Heat stimulation can promote osteoblast differentiation and bone formation. Combining photothermal therapy and chemotherapy is an effective strategy for treating rheumatoid arthritis (RA). Herein, we prepared chitosan/gelatin/β-glycerophosphate-melanin-methotrexate (CMM) hydrogel that could be used to perform simultaneous chemotherapy and photothermal therapy for patients with RA. The CMM solution was successfully converted to a gel state at body temperature. Due to intrinsic photothermal properties of melanin, CMM hydrogel exhibited effective temperature increase both in vitro and in vivo with increasing time of near-infrared (NIR) laser irradiation. After NIR laser irradiation, 50 % of methotrexate was rapidly released from the hydrogel within 3 h. Its release rate showed an instantaneous increase with additional NIR laser irradiation. After CMM hydrogel was injected directly into the paw joint of each collagen-induced arthritis (CIA) mouse followed by irradiation with a NIR laser (808 nm, 0.5 W/cm

The development of a guided bone regeneration (GBR) membrane with non-mammalian fish collagen has the advantage of low risk for transmission of infectious diseases in tissue regeneration. In this work, a fish collagen/gellan gum and bone graft material (FC/GG-BGM) composite GBR membrane were fabricated through solution blending and casting procedures in a vacuum. The membranes were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy observation (SEM), and atomic force microscope (AFM) analyses. FT-IR results suggested that ionic interactions were formed between FC and GG both in composite powder and membranes. In vivo experiments showed that these FC/GG-BGM composite membranes could generate osteoblast minerals and promote loose bone calcification, thus accelerating bone regeneration. At 2 weeks, the defected site of rats treated with FC/GG-BGM membrane (0.377 ± 0.012 mm3) showed higher regeneration than that of rats treated with the bovine collagen membrane (0.290 ± 0.015 mm3) and control rats without membrane (0.160 ± 0.008 mm3). Compared with bovine collagen membrane, the FC/GG-BGM composite membrane displays better bone regeneration ability. Therefore, FC/GG-BGM composite membrane is suitable as a GBR membrane for bone regeneration.

In this study, biodegradable biomaterials were prepared by using inulin (INL), PVA and plasticizers (citric acid (CA), glycerol (GL) and thiamine (TH)) with UV curing process. INL was extracted from Jerusalem artichoke flour using hot water extraction method. Extracted INL and INL/PVA biomaterials were characterized by TLC, FT-IR, and SEM analysis. Physical properties such as mechanical and water resistance properties of biomaterials prepared with UV curing time from 0 to 20 min and types of plasticizers were investigated. Their antimicrobial activities, biodegradability, and application of coating materials for foods were also determined. Results indicated that their physical properties were improved by the UV curing process. In addition, physical properties of TH-added biomaterials were 1.5 to 2 times higher than those of GL-added and CA-added biomaterials. Biodegradability in soil revealed that biomaterials were degraded by about 20–40% after 140 days.

Solanum nigrum L., which has anti-inflammatory and antibacterial properties, has been used for disease prevention and treatment. Although the various effects of Solanum nigrum L. are well k...

To minimize side effects and increase drug efficacy, a novel strategies are needed to facilitate rapid drug release at the lesion site. In this study, a nanovesicle composed of phospholipid...

In this work, biodegradable biomaterial films for sulindac (SLD) recognition are synthesized from mungbean starch (MBS), PVA, and plasticizers by using UV irradiation process and casting methods. The optimal UV irradiation time for the preparation of SLD imprinted biomaterials films was about 30 min. Mechanical properties, recognition ability, and SLD release property for prepared films were investigated. From the results of recognition ability, we verified that these SLD imprinted biomaterial films have the binding site for SLD. The release properties of SLD was examined with the change of pH and temperature. The results indicate that the SLD release in pH 10.0 was higher than in pH 4.0. SLD release was also evaluated using an artificial skin. Results of the artificial skin test verified that SLD was released constantly for 20 days.

The aim of this study was to investigate the effect of the Carbopol® hydrogel containing propolis (CHP) on wound healing in a rat model. CHP extracts inhibited nitric oxide production induced by lipopolysaccharide in RAW264.7 cells with a concentration-dependent manner. Wounds were prepared through excision to remove full-thickness skin of rats k]and then were covered with CHP. The covered wounds showed significantly rapid contraction and closure. Histological tissue examination indicated that CHP induced advanced granulation tissue formation and re-epithelialization in the wound. These results indicate that CHP may be helpful for the promotion of wound healing.

The aim of this experimental investigation is to develop electrically conductive controlled low strength materials (CLSM) using both fly ash with high content of unburned carbon particles (HCFA) and copper slag as a fine aggregate, both of which are waste materials with low reuse rate. Various experiments, including flow consistency test, bulk density measurement, unconfined compression test, and electrical conductivity ( σ mix ) measurement were performed on the developed electrically conductive CLSM. For comparison with the results of the developed conductive CLSM, various experiments were also performed on CLSM containing electrically nonconductive particles (low carbon fly ash (LCFA) and sand). The results of this study demonstrate that σ mix of the tested CLSM specimens increases with increasing copper slag fraction in aggregate and the measured σ mix of the CLSM based on HCFA is greater than that with LCFA because both HCFA (or unburned carbon particles) and copper slag are electrically conductive. The measured flow consistency, bulk density, and unconfined compressive strength (UCS) of conductive CLSM were comparable with those of nonconductive CLSM. Therefore, the electrically conductive CLSM can be developed using both HCFA and copper slag. Finally, the relationship between UCS and 1/ σ mix was also investigated in this study.

This paper reports on a method of preparing chitosan-based films to which sulfosuccinic acid (SSA) is added for crosslinking agent with/without UV curing treatment and applications of a coating materials for foods. The physical, thermal, and optical properties of the UV cured chitosan-based films are investigated including their tensile strength (TS), elongation at break (%E), degree of swelling (DS), solubility (S), and water vapor absorption as well as their biodegradability in soil and applicability of the coating on a fruit. We also evaluated the physical properties of the prepared films to which glycerol (GL), xylitol (XL), and sorbitol (SO) are added to be used as plasticizers. The surface and topography of the prepared films are investigated by scanning electronic microscopy (SEM) and atomic force microscopy analysis (AFM). The results indicate that the films UV cured for 20min possess optimal physical and thermal properties compared to that of non-cured films. The mechanical, thermal, and water barrier properties of SO-added film are also found to be superior to other films with added GL and XL. The degree of biodegradability revealed that the films are degraded by about 40-65% after 220days.

We examined the therapeutic effect of chitosan nanoparticles (CHI) incorporating vascular endothelial growth factor (VEGF) on hindlimb ischemia using single photon emission computed tomography (SPECT) perfusion imaging. Rats (n=24) were divided randomly into four groups of six: control, VEGF, CHI, and CHI incorporated with VEGF (CHI-VEGF). The right femoral artery was ligated to block blood flow, and SPECT perfusion images were obtained every week for 4 weeks. The morphology of the synthesized CHI was identified as a spherical shape with an even size distribution (range, 93–250 nm). The VEGF loading efficiency in CHI was 8.6±2.1%. Upon injection into the femoral artery, 17.6±8.2% of the 99mTc-labeled CHI-VEGF administered remained in the ischemic lesion. The restoration of blood flow (ratio of ischemia to normal) measured by SPECT perfusion imaging was greater in animals treated with CHI-VEGF compared to that in the control (p=0.028), VEGF (p=0.010), and CHI (p=0.011) groups. Administering CHI-VEGF had a significant therapeutic effect in a hindlimb ischemic rat model. 99mTc gamma perfusion imaging was useful to study therapeutic angiogenesis. Open image in new window

Chitosan hydrogels (CSH) formed through ionic interaction with an anionic molecule are suitable as a drug carrier and a tissue engineering scaffold. However, the initial burst release of drugs from the CSH due to rapid swelling after immersing in a biofluid limits their wide application as a drug delivery carrier. In this study, alginate layering on the surface of the doxorubicin (Dox)-loaded and I-131-labeled CSH (DI-CSH) was performed. The effect of the alginate layering on drug release behavior and radiolabeling stability was investigated. Chitosan was chemically modified using a chelator for I-131 labeling. After labeling of I-131 and mixing of Dox, the chitosan solution was dropped into tripolyphosphate (TPP) solution using an electrospinning system to prepare spherical microhydrogels. The DI-CSH were immersed into alginate solution for 30 min to form the crosslinking layer on their surface. The formation of alginate layer on the DI-CSH was confirmed by Fourier transform infrared spectroscopy (FT-IR) and zeta potential analysis. In order to investigate the effect of alginate layer, studies of in vitro Dox release from the hydrogels were performed in phosphate buffered in saline (PBS, pH 7.4) at 37 °C for 12 days. The radiolabeling stability of the hydrogels was evaluated using ITLC under different experimental condition (human serum, normal saline, and PBS) at 37 °C for 12 days. Formatting the alginate-crosslinked layer on the CSH surface did not change the spherical morphology and the mean diameter (150 ± 10 μm). FT-IR spectra and zeta potential values indicate that alginate layer was formed successfully on the surface of the DI-CSH. In in vitro Dox release studies, the total percentage of the released Dox from the DI-CSH for 12 days were 60.9 ± 0.8, 67.3 ± 1.4, and 71.8 ± 2.5 % for 0.25, 0.50, and 1.00 mg Dox used to load into the hydrogels, respectively. On the other hand, after formatting alginate layer, the percentage of the released Dox for 12 days was decreased to 47.6 ± 1.4, 51.1 ± 1.4, and 57.5 ± 1.6 % for 0.25, 0.50, and 1.00 mg Dox used, respectively. The radiolabeling stability of DI-CSH in human serum was improved by alginate layer. The formation of alginate layer on the surface of the DI-CSH is useful for improving the drug release behavior and radiolabeling stability.

Angiogenesis plays a major role in various physiological and pathological situations. Thus, an angiogenic therapy with vascular endothelial growth factor (VEGF) has been commonly recommended as a representative therapeutic solution to recover the insufficient blood supply of collateral vessels in an ischemic lesion. In this study, the injection method and injection time point of VEGF proteins were focused to discover how to enhance the angiogenic effect with VEGF.Mouse models (n = 15) were divided into control, VEGF treatment by intra-venous injection (VEGF-IV) and VEGF treatment by intra-muscular injection (VEGF-IM). Right proximal femoral arteries of mice were firmly sutured to obstruct arterial blood-flow. In the VEGF-IV treatment group, VEGF proteins were injected into the tail vein and, in the VEGF-IM treatment group, VEGF proteins were directly injected into the ischemic site of the right thigh after postoperative day 5, 10, 15, 20 and 25 follow-ups. Blood-flow images were acquired by (99m)Tc Gamma Image Acquisition System to compare the ischemic-to-non-ischemic bloodstream ratio at postoperative days 5, 15, and 30.VEGF-IM treatment significantly induced higher an angiogenic effect rather than both the control group (P = 0.008) and VEGF-IV treatment group (P = 0.039) at the 30th day.During all experiments, angiogenesis of VEGF-IM treatment represented the most evident effect compared with control and VEGF-IV group in a mouse model of hindlimb ischemia.

A new approach to the surface engineering of superparamagnetic iron oxide nanoparticles (SPIONs) may encourage their development for clinical use. In this study, we demonstrated that nonpolymeric surface modification of SPIONs has the potential to be an advanced biocompatible contrast agent for biomedical applications, including diagnostic imaging in vivo. Methods: Adenosine triphosphate (ATP), which is an innate biomaterial derived from the body, was coated onto the surface of SPIONs. An in vivo degradation study of ATP-coated SPIONs (ATP@SPIONs) was performed for 28 d. To diminish phagocytosis, ATP@SPIONs were surface-modified with gluconic acid. We next studied the ability of the SPIONs to serve as a specific targeted contrast agent after conjugation of cMet-binding peptide. The SPIONs were conjugated with Cy5.5 and labeled with 125I for multimodality imaging. In vivo and in vitro tumor-targeted binding studies were performed on U87MG cells or a U87MG tumor model using animal SPECT/CT, an optical imaging system, and a 1.5-T clinical MR scanner. Results: ATP@SPIONs showed rapid degradation in vivo and in vitro, compared with ferumoxides. ATP@SPIONs modified with gluconic acid reduced phagocytic uptake, showed improved biodistribution, and provided good targetability in vivo. The gluconic acid–conjugated ATP@SPIONs, when conjugated with cMet-binding peptide, were successfully visualized on the U87MG tumors implanted in mice via multimodality imaging. Conclusion: We suggest that ATP@SPIONs can be used as a multiplatform to target a region of interest in molecular imaging. When we consider the biocompatibility of contrast agents in vivo, ATP@SPIONs are superior to polymeric surface–modified SPIONs.

The imaging of sentinel lymph nodes (SLN) has been researched for its role in assessing cancer progression and postsurgical lymphedema. Indocyanine green (ICG) is a near-infrared (NIR) optical dye that has been approved by the Food and Drug Administration. It is known that liposome-encapsulated ICG (LP-ICG) has improved stability and fluorescence signal compared with ICG. We designed mannosylated liposome-encapsulated ICG (M-LP-ICG) as an optical contrast agent for SLN. M-LP-ICG has a higher UV absorbance spectrum and fluorescence intensity than LP-ICG. The stability of M-LP-ICG measured in 50% fetal bovine serum solution by a dialysis method was better than that of LP-ICG. M-LP-ICG demonstrated a high uptake in RAW 264.7 macrophage cell because the density of mannose is high. There were differences between M-LP-ICG and glucosylated liposome-encapsulated ICG (G-LP-ICG), which are geometrical isomers. The result of an inhibition study of M-LP-ICG showed a statistically significant decrease in uptake in RAW 264.7 cells after either co-treatment or pre-treatment with D-(+)-mannose as an inhibitor. Results from an in vitro experiment demonstrated that M-LP-ICG was specifically taken up by macrophage cells through the mannose receptor on its surface. The time-series images acquired from a normal mouse model after subcutaneous injection showed that the signal from M-LP-ICG in SLN and other organs appeared early and disappeared quickly in comparison with signals from LP-ICG. Not only the sentinel but also the draining lymph nodes were observed partly in M-LP-ICG. M-LP-ICG appears to increase the specificity of uptake and retention in macrophages, making it a good candidate contrast agent for an optic imaging system for SLN and the lymphatic system.

In this study, we investigated that when γ-cyclodextrin (γ-CD) forms the inclusion complexes for fish oils, the oxidation stability and retardation of odor can be effectively enhanced through the addition of sodium caseinate (SC). In order to evaluate the oxidative stability and the odor-masking effect, the inclusion complexes of γ-CD and SC incorporating fish oils at various ratios were thermally-oxidized for 5 days at a storage temperature of 55°C. The use of SC on the inclusion complexes of γ-CD could improve the oxidative stability of fish oils and the masking effect of the odor. When the inclusion complexes for fish oils were composed with 80% of γ-CD and 20% of SC, the improvement effect of the oxidative stability was better compared with the complexes of other ratios. Therefore, the use of γ-CD and SC can potentially protecting sensitive ingredients such as EPA and DHA in the food industry.

In this study, we investigated the effect of a polyvinyl alcohol-blended pectin hydrogel (PVA-PT HG) containing the extracts of Hippophae rhamnoides L. (H. rhamnoides L.) leaves on wound healing in a rat model. The total phenolic content in the extract solution was 40.64±2.7 GAE mg/g and that of flavonoids was 13.15±1.8 QE mg/g. Of the total flavonoids in HGs, 61.6 and 50.0% were released at pH 5.5 and 7.4 after 60min. In rat acute wound models, the wound size was reduced significantly and the recovery rate was significantly higher after treatment with HG containing the extracts, compared with treatment with the control and HG only. The wound healing effects of the HG containing the extracts were confirmed by histological evaluation of the wound tissue. Therefore, HG containing extracts from H. rhamnoides L. leaves enhanced wound healing effectively, and so may be developed as a cover to promote wound healing.

The prevention of undesired abdominal wall adhesion after surgery was investigated using polysaccharide hydrogels as physical barriers. Hydrogels of curdlan, gellan gum, and a mixture of the two were prepared as films and their swelling, degradation, and gel strength were measured. The hydrogels were applied to 1×2 cm2 abraded areas of the peritonea and ceca of rats. The hydrogel extracts showed no cytotoxicity to RAW 264.7 macrophage cells up to 1% (v/v) concentration. The curdlan and gellan gum hydrogels resulted in less post-operative adhesion of the peritoneum and cecum than shown by non-treated rats without physical barriers, but they could not completely separate the injured wall from the cecum. The mixed hydrogel resulted in less adhesion than either pure hydrogel and could be used as a physical barrier to prevent abdominal post-operative adhesion during healing. Open image in new window

The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor and plays an important role in carcinogenesis. In this study, the epidermal growth factor receptor binding peptide (EGBP) was identified using a phage display method and evaluated in U87MG cells in order to investigate the possibility to target the EGFR using an optical imaging system. Cyanine dye 5.5 (Cy5.5) was conjugated with EGBP-GGG-SC, EGBP-AOC-SC, and EGBP-AM2BA-SC. Cellular binding study of EGBP-Linker-Cy5.5 conjugates or (125)I-EGBP-Linker compounds was performed in U87MG cells. Optical imaging studies were performed in U87MG bearing mice. Three of seven clones from the 12-mer peptide library showed a specific binding affinity to rhEGFR, and they encoded the same 12 amino acid peptide sequence, FPMFNHWEQWPP. Confocal images show that the fluorescent signal of EGBP-Linker-Cy5.5 conjugates was decreased in the order: EGBP-AOC-Cy5.5≫EGBP-AM2BA-Cy5.5>EGBP-GGG-Cy5.5. EGBP-AOC-Cy5.5 appeared in cell cytoplasm and surface, and it was inhibited by free EGBP apparently. The cellular binding of EGBP-AOC-Cy5.5 exhibited a higher average radiance value than EGBP-GGG-Cy5.5 and EGBP-AM2BA-Cy5.5. Among various (125)I-EGBP-Linker compounds, EGBP-GGG showed a higher binding than other compounds. However, uptake of (125)I-EGBP-AOC was clearly inhibited by free EGBP in inhibition study. In an in vivo study, the fluorescent signal of EGBP-AOC-Cy5.5 treated mouse was mainly detected in the tumor and kidney. Among the three derivatives, EGBP-AOC-Cy5.5 was the optimized optical imaging agent for U87MG EGFR positive tumors in the animal model. This study demonstrated the EGBP-Linker-Cy5.5 conjugates may be useful as a potential EGFR target optical probe.

Chang-Moon Lee,1–4,* Hwan-Jeong Jeong,1–4,* Kuk-No Yun,1–3 Dong Wook Kim,1–4 Myung-Hee Sohn,1–4 Jong Kwon Lee,5 Jayoung Jeong,5 Seok Tae Lim1–4 *These authors contributed equally to this work.1Department of Nuclear Medicine; 2Cyclotron Research Center; 3Research Institute of Clinical Medicine; 4Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Osong-Eup, Chungchungbuk-Do, Republic of KoreaBackground: Understanding how nanomaterials are distributed in the body after exposure is important for assessing whether they are safe. In this study, we investigated the behavior and accumulation of nanoscaled and submicron-scaled zinc oxide (ZnO) particles in the body using optical imaging following oral exposure.Methods: To trace these nanoparticles in the body, ZnO nanoparticles were conjugated with a monoreactive hydroxysuccinimide ester of Cy5.5 (Cy5.5-NHS), and the conjugation-stabilizing effect of Cy5.5 on the nanoparticles was evaluated in simulated gastric fluid (pH 1.2) for 7 hours. To compare the distribution of Cy5.5-NHS and Cy5.5-conjugated ZnO nanoparticles, Cy5.5-NHS 0.5 mg/kg and Cy5.5-conjugated ZnO nanoparticles 250 mg/kg were administered orally to healthy rats. We collected blood from the rats at predesignated time points for 7 hours after administration, and optical imaging studies were performed at 1, 2, 3, 5, and 7 hours after dosing. To investigate the extent of nanoparticle accumulation in the organs and tissues, the mice were sacrificed at 23 hours after administration, and the organs were removed and imaged.Results: Cy5.5-conjugated ZnO nanoparticles were stable in simulated gastric fluid for 7 hours. The signal intensity of Cy5.5-NHS in blood was highest 3 hours after oral administration, and Cy5.5-conjugated ZnO nanoparticles showed the highest signal intensity in blood 5–7 hours after administration. In vivo optical images indicated that Cy5.5-NHS showed optical signals in the lung, liver, and gastrointestinal tract after oral administration, whereas Cy5.5-conjugated ZnO nanoparticles were seen only in the gastrointestinal tract. Seven hours following administration, biodistribution studies demonstrated that Cy5.5-NHS accumulated in the lung and liver, and Cy5.5-conjugated ZnO nanoparticles resulted in a strong signal in the kidney and liver. Different-sized ZnO nanoparticles showed dissimilar patterns of biodistribution in ex vivo optical images.Conclusion: ZnO nanoparticles are absorbed into the tissues following oral exposure and their behavior can be monitored and evaluated using optical imaging.Keywords: zinc oxide nanoparticles, biodistribution, optical imaging, oral administration

In this work, the aim was to prepare and characterize a magnetofluorescent polymeric nanoparticle for prostate cancer imaging in vivo.Glycol chitosan (GC) was chemically modified with N-acetyl histidine (NAHis) as a hydrophobic moiety, and bombesin (BBN) was conjugated to the hydrophobically modified GC for use in targeting gastric-releasing peptide receptors (GRPR) overexpressed in prostate cancer cells. NAHis-GC conjugates were labeled with the near-infrared (NIR) fluorophore Cy5.5 (C-NAHis-GC conjugate).BBN-conjugated C-NAHis-GC nanoparticles (BC-NAHis-GC nanoparticles) showed significantly higher binding to the PC3 cell surface than nanoparticles without BBN, and the cellular binding was clearly inhibited by BBN. The tumor-to-muscle ratios of C- and BC-NAHis-GC nanoparticles were 2.26 +/- 0.66 and 5.37 +/- 0.43, respectively. The tumor accumulation of BC-NAHis-GC nanoparticles was clearly reduced by co-injection of BBN. Further, iron oxide nanoparticles (IO) were loaded into BC-NAHis-GC nanoparticles to investigate the possibility of use as a probe for MRI. IO-BC-NAHis-GC nanoparticles were well observed in the PC3 cells, and the blocking with BBN significantly reduced the cellular binding of the nanoparticles.These results demonstrate that the BBN conjugation to NAHis-GC nanoparticles improves their tumor accumulation in PC3-bearing mice in comparison to nanoparticles without BBN, suggesting that BC-NAHis-GC nanoparticles may be useful for prostate cancer imaging.

Hepatocyte-specific targeting agents are useful for evaluation of the hepatocytic function and the monitoring of disease progress. Superparamagnetic iron oxide nanoparticles (SPION) bearing terminal galactose groups exhibit a high affinity for the asialoglycoprotein receptor on the hepatocyte surface. In this study, we synthesized and characterized the dual probe SPION detectable by both nuclear and MR imaging modality for specifically targeting hepatocytes in vivo. SPION with 12-nm diameter were functionalized with dopamine. Surface modification of the SPION was performed to target asialoglycoprotein receptor on hepatocytes, using lactobionic acid. Transmission electron microscope images demonstrated that SPION displayed highly uniform characteristics in terms of both particle size and shape. The X-ray diffraction pattern of SPION revealed a nanocrystal structure of magnetite. To radiolabel the magnetite with (99m)Tc, diethylenetriaminepentaacetic acid was conjugated to unreacted functional groups of dopamine. (99m)Tc-labeled lactobionic acid-SPION showed high accumulation in liver, with 38.43 +/- 6.45% injected dose per gram. In MR imaging, the reduction of the T(2) signal in the liver by lactobionic acid-SPION was approximately 50.8 +/- 7.3%. Competition studies and transmission electron microscope images of liver tissues demonstrated that the lactobionic acid-SPION were localized in hepatocytes. Therefore, the lactobionic acid-SPION may be used as a hepatocyte-targeted dual contrast agent for both nuclear and MR imaging.

The aim of this study was to develop a novel polymeric magnetic nanoprobe as an MRI contrast agent to target hepatocytes, as well as to evaluate the targeting ability of the nanoprobe with MRI in vivo . Superparamagnetic iron oxide nanocrystals (SPIONs) were synthesized by a thermal decomposition and seed growth method. An 1-ethyl-3-(3-(dimethylamino)-propyl) carbodiimide (EDC)-mediated reaction coupled water-soluble chitosan (WSC) to linoleic acid (LA). Twelve-nanometer-sized SPIONs were incorporated into the core of self-assembled WSC–LA nanoparticles. The morphology and size distribution of the SPION-loaded WSC–LA nanoparticles (SCLNs) were determined by transmittance electron microscopy (TEM) and dynamic light scattering (DLS), respectively. The encapsulation of SPIONs in the WSC–LA nanoparticles reduced the cytotoxicity of bare iron particles and enhanced their dispersion ability in water. The clustering of SPIONs into WSC–LA nanoparticles showed ultrasensitive magnetic behavior. After in vivo intravascular SCLN injection, MRI revealed relative signal enhancement in the liver. The localization of SCLN in hepatocytes was confirmed by Prussian blue staining and TEM analysis. We have successfully developed an ultrasensitive SCLN that effectively targets hepatocytes. The SCLN can be used as a contrast agent to aid in the diagnosis of hepatic diseases.

We have synthesized the SPION coated with CMC and investigated the stability in water,T 2 relaxation rate and cytotoxicity. The coating with CMC improved the stability in water and reduced the cytotoxicity to cell viability. Furthermore, the CMC-coated SPION showed superparamagnetic behaviors. The CMC-coated SPION may be used for cellular andin vivo imaging. When CMC are chemically modified for conjugation of specific ligand, the CMCcoated SPION may have a great potential for biomedical applications.

The aim of this work was to develop and evaluate solid lipid nanoparticles (SLN) containing all-trans-retinoic acid (ATRA) for topical delivery. SLN composed of coconut oil and curdlan improved the suspension instability of ATRA in aqueous solution. The photodegradation of ATRA by light was reduced by incorporation in SLN. The loading efficiency of ATRA in SLN was higher than 95% (w/w). The amounts of ATRA released from SLN at 4 °C and at 37 °C were less than 15% and more than 60% (w/w) for 96 h, respectively. The ATRA-loaded SLN can be used as a potential carrier for topical delivery.

Transferrin is one of acute phase reactants in inflamed lesion. Expression of transferrin receptor is increased in activated macrophage during inflammation process. Conjugates of target ligand with novel water-soluble chitosan for fast excretion of background radioactivity have been shown to be selectively taken up via the target molecules. In this study, radiolabeled 99mTc–Transferrin conjugate was synthesized and evaluated its efficacy in vivo as a targeted agent for the rapid detection of inflamed lesion that expresses relatively high level of transferrin receptors. Transferrin was conjugated with HYNIC-chitosan and radiolabeled with 99mTc. The biodistribution and scintigraphic images with the 99mTc–HYNIC–chitosan–Transferrin conjugate (99mTc–Tfc) were studied in a murine infection model in which the infection was induced with Escherichia coli (2 × 106 colonies). The %ID/g was as follows: 1.612 ± 0.098, 2.473 ± 0.202 and 2.617 ± 0.646% at 30, 120 min and 6 h after injection, respectively. Gamma camera ...

The aim of the present study was to evaluate the utility of pullulan acetate microparticles (PAMs), chitosan micropaticles (CMs), and dipalmitoylphosphatidyl-serine-liposomes (PS-Lip) as oral carriers for delivery to the intestinal Peyer's patches (PPs). To monitor PP delivery after oral administration, PAMs, CMs, and PS-Lip were radiolabeled with 99mTc. Radiolabeling efficiencies of the particles were 95±2.5% (PAMs), 87±4.3% (CMs), and 77.2±5.8% (PS-Lip). In delivery studies to the PPs, the percentage of PS-Lip taken up to the PPs was 3.8 × 10−3±0.3% of the administered dose with PS-Lip group showed significantly high uptake compared to the PAM and CM groups. These results suggest that PS-Lip may be used as a potential system for developing an oral delivery carrier. Drug Dev. Res. 67:884–889, 2006. © 2007 Wiley-Liss, Inc.

Drug delivery to the lymphatic system may be important in terms of the treatment with lymphatic involvement, such as tumor metastases and immunization. Especially, drug transport via the intestinal lymphatics after oral administration has been attracted lots of interests. The purpose of this study was to prepare cyclosporin A (CSA)-loaded liposomes, with different characteristics, and evaluate their ucoadhesivity. Three liposome preparations were formulated: cationic stearylamine liposomes (SA-Lip), anionic phosphatidylserine liposomes (PS-Lip), polymer (chitosan)-coated liposomes (CS-Lip), and characterized. The liposome preparations were found to be spherical in shape, with PS-Lip being the smallest. The liposome preparations exhibited entrapment efficiencies in the order: PS-Lip (52.5±2.9%)>SA-Lip (48.8±3.3%)> CS-Lip (41.7±4.2%). Finally, mucoadhesive tests were carried out using rat intestine, with SA-Lip (67%) showing the best adhesive rate of the three preparations (PS-Lip: 56%, CS-Lip: 61%). These results suggest that a positive charge on the surface of drug carriers may be an important factor for the intestinal drug delivery.

The aim of this study was to formulate a sustained release system for indomethacin (IND) with rosin gum obtained from a pine tree. Rosin microparticles were prepared by a dispersion and dialysis method without the addition of surfactant. In order to investigate the influence of solvents on the formation of colloidal microparitcles, various solvents like ethanol, DMF, DMAc, and acetone were used. The rosin microparticles containing IND were characterized by X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The morphologies of rosin microparticles observed by scanning electron microscopy (SEM) were spherical. The solvents used to dissolve rosin significantly affected the drug content and drug release rate of IND. The release behaviors of IND from the rosin microparticles were dependent on the drug content and size of the particles. Rosin microparticles with a higher drug content and of a larger particle size had a slower drug release rate. Also, the IND release rate from the rosin microparticles could be regulated by the rosin content in the microparticles. From these results, rosin microparticles have the potential of being used as a sustained release system of IND.

Drug delivery systems that are based on pectin have been studied for colon specific delivery using the specific activity of colon microflora. The aim of this study was to design a novel method of manufacturing pectin microspheres without oils and surfactants and to investigate the potential use of the pectin microsphere as an oral colon-specific drug carrier. The pectin microspheres were successfully formed using the spray drying method and crosslinking with calcium chloride. From the crosslinked pectin microspheres, indomethancin (IND) release was more supressed than its release from non-crosslinked microspheres. In a low pH (pH 1.4) environment, the pectin microspheres released IND at an amount of about 18±2% of the total loaded weight for 24h while the release rate of IND was stimulated at neutral pH (pH 7.4). IND release from the pectin microspheres was increased by the addition of pectinase. The results clearly demonstrate that the pectin microspheres that were prepared by the spray drying and crosslinking methods are potential carriers for colon-specific drug deliveries.

Monitoring of the behavior of metal nanoparticles in the body following exposure is very important for investigation of the physiological fates and safety of these nanoparticles. In this study, we investigated the behavior and accumulation of nano-scaled ZnO (20 nm) and submicro-scaled ZnO (100 nm) particles in organic tissues after oral administration using PET imaging. Both types of ZnO nanoparticle (20 or 100 nm) were labeled with the radionuclide (18)F in high yield via 'click reaction'. (18)F labeling on the ZnO nanoparticles was maintained stably in simulated gastric fluid (pH 1.2) for 7 h. PET images indicated that (18)F and (18)F-ethoxy azide showed radioactivity in the bone and bladder 3 h after oral administration, whereas radioactivity for (18)F-labeled ZnO nanoparticles was seen only in the gastrointestinal (GI) tract. At 5 h post-administration, biodistribution studies demonstrate that (18)F accumulated in the bone (10.19 ± 1.1%ID g(-1)) and (18)F-ethoxy azide showed radioactivity in the bone (7.55 ± 0.6%ID g(-1)), liver, and brain (0.94 ± 0.3%ID g(-1)). Unlike (18)F and (18)F-ethoxy azide, (18)F-labeled ZnO nanoparticles showed radioactivity in the lung, liver and kidney including the GI tract. Submicro-scaled (18)F-labeled ZnO nanoparticles (100 nm) showed stronger radioactivity in the liver and kidney compared to nano-scaled (18)F-labeled ZnO nanoparticles (20 nm). In conclusion, PET imaging has the potential to monitor and evaluate the behavior of ZnO nanoparticles absorbed in organic tissues following oral exposures.

Scalp burns can be caused by hair bleaching with excess procedures such as unnecessary heating and excessive treatment with bleaching agents. The aim of this study was to investigate the morphological and histological changes of the hair and skin after bleaching. Ammonium persulfate and hydrogen peroxide (6% or 9%) solution mixed at a ratio of 1:2 (weight ratio) were sufficiently applied to human hairs and rat skin. The bleached hairs were brightened up to yellow by increasing the concentration of hydrogen peroxide and time of bleach treatment. After bleaching, scanning electron microscopy (SEM) was used to observe that the cuticle scales of the hairs were irregular and lifted. The mechanical properties of the bleached hairs, such as tensile strength and elongation, were slightly different than the untreated hairs. The tested rat skin showed severe swelling after treatment of the bleaching agent (9% hydrogen peroxide). The rat skin bleached with 9% hydrogen peroxide exhibited epidermal thinning and subepidermal vesicle formation. The extracellular matrix of the skin was seriously disrupted after bleaching. Therefore, the use of only suitable bleaching procedures is suggested in order to avoid injuries.

Hydrocortisone (HC)-loaded rosin nanoparticles were prepared by a dispersion and dialysis method without addition of surfactant. They were spherical: 167-332 nm diam. The drug was loaded approximately 50% of initial feeding amount in all formulation. Release of hydrocortisone from the nanoparticles in vitro gradually decreased with increasing initial rosin content at pH 7.4. HC was also released very slowly at pH 1.2. Nanoparticles based on rosin thus are potentially useful as a drug delivery system.