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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.

The purpose of this study was to develop and preliminarily evaluate phospholipid-shelled nanodroplets (NDs) encapsulating perfluoropentane (PFP) and radioactive 64Cu as a hybrid positron emission tomography (PET)-ultrasound (US) probe. PFP NDs were fabricated by mixing liquid-phase PFP with a phospholipid solution. The 64Cu was encapsulated into the NDs in a size-controlled manner by exploiting the hydrophobicity of 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) using a vial mixer and an extruder. The fabricated 64Cu-loaded PFP NDs (64Cu-PFP NDs) were evaluated using in vitro/in vivo PET-computed tomography (PET-CT), US imaging and transmission electron microscopy. In the in vitro PET images, the 64Cu-PFP NDs were observed as a hot spot in the lower section of the test tube. In the acquired US images, the mean region of interest brightness values of 64Cu-PFP NDs were revealed by their strong echo image. In a tumor-bearing mouse animal model, tumor uptake of the 64Cu-PFP NDs was low, that is, approximately 65%, compared with that of only free 64Cu, as determined by PET-delayed imaging analysis. The dual-function concept of the NDs is expected to contribute to the prognosis and effectiveness of therapy by fusing the science and technology of nuclear medicine and US.

I-131-labeled chitosan microhydrogels (I-131-CMH) that are retained at an injection site without leaking free I-131 into normal tissue can provide opportunities to improve cancer therapy. This study focuses on the development of doxorubicin-loaded I-131-CMH (Dox-I-131-CMH) for use in radiochemotherapy against cancer. The radiolabeling of I-131-CMH was found to be stable over a period of 2 weeks with no disassociation of free I-131, and Dox showed a sustained release from the CMH. When I-131-CMH were injected into the thigh muscle or tumor tissue, in vivo gamma imaging showed a retention at the injection site with no significant leakage of I-131 into other areas of normal tissue, and after an intrahepatic arterial injection, I-131-CMH were selectively retained in the liver. Dox-I-131-CMH had significant synergistic therapeutic effects of radiation and chemotherapy on mouse breast cancer models. In this regard, Dox-I-131-CMH may be a new alternative agent for cancer therapy.

Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its usefulness and utility in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling, but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) was combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers could be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibited enhanced growth, proliferation, vascular endothelial growth factor (VEGF) production and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds, compared to MSCs cultured on SF or GelMA alone nanofibers could greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis related immunofluorescence staining indicated SG7 scaffolds demonstrated enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.

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

Background Heat generation in a drug delivery carrier by exposure to near-infrared (NIR) light with excellent tissue transmittance is an effective strategy for drug release and tumor therapy. Because liposomes have amphiphilic properties, they are useful as drug carriers. Liposomes are also very suitable for drug delivery strategies using heat generation by NIR laser because lipid bilayers are easily broken by heat. Thermally generated bubbles from liposomes not only induce drug release, but also enable ultrasound imaging. Methods Melanin, perfluorohexane (PFH), and 5-fluorouracil (5-FU)-loaded liposomes (melanin@PFH@5-FU-liposomes) that can generate heat and bubble by NIR laser irradiation were prepared by a thin film method. Conversion of light to heat and bubble generation of melanin@PFH@5-FU-liposomes were evaluated using an infrared (IR) thermal imaging camera and an ultrasound imaging system both in vitro and in vivo. To investigate tumor therapeutic effect, NIR laser of 808 nm was used to irradiate tumor site for 10 min after injecting melanin@PFH@5-FU-liposome into tail veins of CT26-bearing mice. Results Melanin@PFH@5-FU-liposomes showed a spherical shape with a size of 209.6 ± 4.3 nm. Upon NIR laser irradiation, melanin@PFH@5-FU-liposomes exhibited effective temperature increase both in vitro and in vivo. In this regard, temperature increase caused a phase transition of PFH to induce bubble generation dramatically, resulting in effective drug release behavior and ultrasound imaging. The temperature of the tumor site was increased to 52 t and contrast was greatly enhanced during ultrasound imaging due to the generation of bubble. More importantly, tumor growth was effectively inhibited by injection of melanin@PFH@5-FU-liposomes with laser irradiation. Conclusions Based on intrinsic photothermal properties of melanin and phase transition properties of PFH, melanin@PFH@5-FU-liposomes exhibited effective heat and bubble generation upon NIR laser irradiation. The elevated temperature induced bubble generation, resulting in contrast enhancement of ultrasound imaging. Melanin@PFH@5-FU-liposomes under NIR laser irradiation induced the death of cancer cells, thereby effectively inhibiting tumor growth. These results suggest that melanin@PFH@5-FU-liposomes can be utilized as a promising agent for photothermal tumor therapy and ultrasound imaging.

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.

Purpose: This study examines the properties and potential commercial value of the pine cones extract when used as bioactive and cosmetics ingredients. Methods: Pine cones were extracted with hot water (WE), 70% ethanol (EE), and supercritical fluid extraction (SFE) to examine their antioxidant properties on the basis of their total polyphenol content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and gas chromatography-mass spectrometry (GC-MS) analysis. The antibacterial properties of the pine cone extract were also studied on 2 types of bacteria. In addition, this study examined the nitric oxide (NO) inhibition effect using RAW 264.7 cells, in which the inflammatory reaction was induced by lipopolysaccharides (LPS), and cell migration activity in the HeCaT cells. Results: The extract obtained with SFE exhibited high antioxidative ability even at low concentration (0.125%). The antimicrobial activity of the of SFE pine cone extract was 12.1±1.04 mm for Staphylococcus aureus (S. aureus ) and 11.8±0.45 mm for Staphylococcus epidermidis (S. epidermidis ). Cytotoxicity evaluation showed cell viability above 80% in all extracts. During the antiinflammatory test, the nitric oxide expression level was low, and it was confirmed by the antiinflammatory effect. The results of the stability test showed that emulsions containing SFE extract were very stable. The pH and high temperature (40℃) of each emulsion containing SFE extract did not considerably change for 30 days. Conclusion: These findings suggest that SFE extract is a possible cosmeceutical material with potent skin regeneration and antiinflammatory properties.

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.

Colorectal cancer is a representative cancer where early diagnosis and proper treatment monitoring are important. Recently, cancer treatment using bacteria has actively progressed and has been successfully monitored using fluorescence imaging techniques. However, because subcutaneous tumor models are limited in reflecting the actual colorectal cancer situation, new imaging approaches are needed to observe cancers growing in the colon. The fluorescence endoscopic approach is an optimal monitoring modality to evaluate the therapeutic response of bacteria in orthotopic colon cancer. In this study, we developed dual-scaled fluorescence endoscopy (DSFE) by combining wide-field fluorescence endoscopy (WFE) and confocal fluorescence endomicroscopy (CFEM) and demonstrated its usefulness for evaluating bacterial therapy. Firstly, the endoscopic probe of DSFE was developed by integrating the CFEM probe into the guide sheath of WFE. Secondly, colorectal cancer tumor growth and tumors infiltrating the fluorescent bacteria were successfully monitored at the multi-scale using DSFE. Finally, the bacterial distribution of the tumor and organs were imaged and quantitatively analyzed using CFEM. DSFE successfully exhibited fluorescent bacterial signals in an orthotopic mouse colon tumor model. Thus, it can be concluded that the DSFE system is a promising modality to monitor bacterial therapy in vivo.

To increase availability for biomedical applications of melanin, especially as a photothermal agent, poly(ethylene glycol) (PEG) was conjugated to melanin in this study. Melanin-PEG conjugate formed self-assembled nanoparticles with mean diameter of 109.3 ± 2.4 nm. Melanin-PEG nanoparticles showed no precipitation in aqueous solution for 7 days. Due to intrinsic photothermal properties of melanin, these melanin-PEG nanoparticles showed good photothermal conversion efficiencies both in vitro and in vivo. When melanin-PEG nanoparticles were injected into tail vein of 4T1-bearing mouse followed by exposure to 808 nm NIR laser at a power density of 1.5 W/cm2, temperature of the tumor region was increased to 48℃ and tumor growth was less than 50 % compared to that of the control group. As a result, tumor growth was suppressed effectively under NIR laser irradiation after intravenous injection of melanin-PEG nanoparticles. PEG conjugation to melanin can broaden the range of biomedical applications of melanin. Resultant melanin-PEG nanoparticles have great potential as photothermal agents for cancer therapy.

Photothermal therapy requires a biocompatible material to absorb near-infrared (NIR) light and generate sufficient heat. Herein, we suggest natural melanin-loaded nanovesicles (melasicles) as photothermal therapeutic agents (PTA) for NIR mediated cancer therapy in vivo. The mean size of these melasicles was 140 ± 15 nm. They showed excellent colloidal stability. After irradiation from 808 nm NIR laser at 1.5 W cm-2, the melasicles showed good photothermal conversion efficiencies both in vitro and in vivo. In drug release study, laser irradiation increased fluidity of vesicle membrane due to photothermal generation from melanin. Initial drug release in the laser irradiation group was higher than that in the no laser irradiation group. After injecting the melasicles into tail veins of CT-26 bearing mice, tumors were suppressed or eliminated after irradiation at 1.5 W cm-2 for 5 min once or twice. These results suggest that melasicles could be used as attractive PTA for cancer therapy and localized drug release.

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.

The photothermal effect is used in a new drug release system to control drug delivery in a specific region. Melanin absorbs near-infrared (NIR) light with a high photothermal conversion efficiency, and as a result, an NIR laser can be used to induced drug release from alginate microparticles containing melanin (ALG-Mel microparticles). The temperature of the ALG-Mel microparticle solution at a concentration of 5mg/mL increased to 38.1°C from 26.0°C after irradiation with 808nm NIR at 1.5W/cm2 for 5min, and this increase in temperature was found to be independent of the ALG-Mel microparticle concentration. After the NIR laser irradiation, 5-fluorouracil (5-FU) was released from the ALG-Mel microparticles to 87.4±0.5% of the total loaded drug for 24h. Without NIR laser irradiation, 5-FU was released from the ALG-Mel microparticles to 60.8±1.5% of the total loaded drug for 24h. These results indicate that NIR laser irradiation can be used with ALG-Mel microparticles as a drug delivery system for release within a target region.

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.