• Archives of Pharmacal Research
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• v.16 no.4
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• pp.312-317
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• 1993

To confirm a new evaluation tedhnique for biodegradability of biopolymer microsphers in vivo condition, magnetic microsphere sytem was adopted for tracing the microspheres injected and lodged in micr. Microsphers of poly(DL-lactic acid), poly(L-alctic acid) and poly(DL-lactide-coglycolide)(PLGA) were prepared by solvent-extraction method and their organ distribution and biodegradation in mice was examined. Magnetic microspheres lodged in mice organs were recollected from the homogenates of mice organs with a constant flow magnetic separation apparatus. Recollected microspheres were observed by scanning electron microscopy and also were assayed for their magnetite ocntent by atomic absorption spectrophotometry to evaluate the biodegradability of polymeric microspheres. This method seems to be practical and simple to estimate the biodegradability of biopolymers over the conventional methods.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.1-12
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• 2004

Initial burst is one of the major challenges in protein-encapsulated microparticle systems. Since protein release during the initial stage depends mostly on the diffusional escape of the protein, major approaches to prevent the initial burst have focused on efficient encapsulation of the protein within the microparticles. For this reason, control of encapsulation efficiency and the extent of initial burst are based on common formulation parameters. The present article provides a literature review of the formulation parameters that are known to influence the two properties in the emulsion-solvent evaporation/extraction method. Physical and chemical properties of encapsulating polymers, solvent systems, polymer-drug interactions, and properties of the continuous phase are some of the influential variables. Most parameters affect encapsulation efficiency and initial burst by modifying solidification rate of the dispersed phase. In order to prevent many unfavorable events such as pore formation, drug loss, and drug migration that occur while the dispersed phase is in the semi-solid state, it is important to understand and optimize these variables.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.237.3-238
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• 2003

Tissue engineering may be adequately defined as the science of persuading the body to regenerate or repair tissue that fail to regenerate or heal spontaneously. In the various techniques of cartilage tissue engineering, the use of 3-dimensional polymeric scaffolds implanted at a tissue defect site is usually involved. These scaffolds provided a framework for cells to attach, proliferate, and form extracellular matrix(ECM). The scaffolds may also serve as carriers for cells and/or growth factors. In the ideal case, scaffold absorb at a predefined rate so that the 3-dimensional space occupied by the initial scaffold is replaced by regenerated host tissue. (omitted)

• Journal of Periodontal and Implant Science
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• v.37 no.3
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• pp.465-478
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• 2007

Various periodontal barrier membranes used in many clinical and experimental fields, and many recent studies of membranes have reported good results. To improve clinical results, selection of barrier membranes is an important factor. So, we need not only to evaluate various barrier mem-branes, but also to understand the property of barrier membranes appropriate to defect characteristics. For this purpose, this study reviewed available literature, evaluated comparable experimental models, and compared various barrier membranes. From above mentioned methods, the following conclusions are deduced. 1. In i-wall periodontal defect models, new bone formation showed a consistent result, almost 30% of the defect size. New cementum formations measured mostly 40% of the defect size, but showed more variations than new bone formations. This seems to be resulted form difference in experimental methods, so standardization in experimental methods is needed for future studies. 2. Application PLGA barrier membrane to periodontal defect demonstrated improved healing in new bone and new cementum. 3. There was a minimal periodontal regeneration with calcium sulfate barrier membrane only. But, there was better healing pattern in combination of calcium sulfate membrane with bone graft material, such as DFDBA, 4. There was no significant difference between the experimental group that used chitosan mem-brane only and the control group. But, in combination with bone graft material for space maintanence, periodontal regeneration was improved. Overall, Space maintenance is a critical factor for Guided tissue regeneration using barrier membranes. Also, a barrier membrane itself that has difficulty in maintaining space, achieved better result when used with graft material.

• Polymer(Korea)
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• v.29 no.3
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• pp.260-265
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• 2005

The initial burst of drug release is an important role in the controlled delivery of drug having hish toxicity and narrow therapeutic ranges. Nanosphere composed of monolayer could not achieve precisely controlled drug release because of the initial burst of drug on surface. In this study, double layered nanosphere was prepared for sustained drug delivery without initial burst. Double layered nanosphere composed of dextran and PLGA was fabricated by using conventional W/O/W double emulsion method. To control surface tension on the outer layer of nanospheres, PVA was used as a surfactant. Release behavior of dextran as model drug was observed as the $3{\times}1$mm wafers formed by compression mould in the deionized water for 7 days. Double layered nanosphere has sustained release behavior, in contast to single layered nanospheres. such as mechanical mixture and dextran nanospheres. Especially, nanosphere containing PVA $0.2\%$ has shown nearly the zero-order release profile. As a result of this study, double layered nanospheres has more sustained release profile of drug without the initial burst and the release behavior of dexoan on tile double layered nanospheres was controlled by the contents of PVA as a surfactant.

• Journal of Chest Surgery
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• v.37 no.6
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• pp.474-481
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• 2004

Background: Tracheal transplantation is necessary in patients with extensive tracheal stenosis, congenital lesions and other oncologic conditions but bears. many critical problems compared to other organ transplantations. The purpose of this study was to develop intestine-cartilage composite grafts for potential application in tracheal reconstruction by free intestinal graft. Material and Method: Hyaline cartilage was harvested from trachea of 2 weeks old New Zealand White Rabbits. Chondrocytes were isolated and cultured for 8 weeks. Cultured chondrocytes were seeded in the PLGA scaffolds and mixed in pluronic gel Chondrocyte bearing scaffolds and gel mixture were embedded in submucosal area of stomach and colon of 3 kg weighted New Zealand White Rabbits under general anesthesia. 10 weeks after implantation, bowels were harvested for evaluation. Result: We identified implantation site by gross examination and palpation. Developed cartilage made a good frame for shape memory. Microscopic examinations included special stain s howed absorption of scaffold and cartilage formation even though it was not fully matured. Conclusion: Intestine-cartilage composite graft could be applicable in the future as tracheal substitute and should be further investigated.

• Journal of Pharmacopuncture
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• v.19 no.1
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• pp.37-44
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• 2016

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9249-9258
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• 2014

Background: The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur-NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrugresistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo. Materials and Methods: First, we determined the MDR-reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions. Results: The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions. Conclusions: Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.

• Macromolecular Research
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• v.10 no.3
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• pp.158-167
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• 2002

In order to endow with new bioactive functionality from small intestine submucosa (SIS) powder as natural source to poly (L-lactide) (PLA) and poly (lactide-co-glycolide) (PLGA) synthetic biodegradable polymer, porous SIS/PLA and SIS/PLGA as natural/synthetic composite scaffolds were prepared by means of the solvent casting/salt leaching methods for the possibility of the application of tissue engineered bone and cartilage. A uniform distribution of good interconnected pores from the surface to core region was observed the pore size of 40~500 ${\mu}{\textrm}{m}$ independent with SIS amount using the solvent casting/salt leaching method. Porosities, specific pore areas as well as pore size distribution also were almost same. After the fabrication of SIS/PLA hybrid scaffolds, the wetting properties was greatly enhanced resulting in more uniform cell seeding and distribution. Five groups as PGA non-woven mesh without glutaraldehyde (GA) treatment, PLA scaffold without or with GA treatment, and SIS/PLA (Code No.3 ; 1 : 12 of salt content, (0.4 : 1 of SIS content, and 144 ${\mu}{\textrm}{m}$ of median pore size) without or with GA treatment were implanted into the back of nude mouse to observe the effect of SIS on the induction of cells proliferation by hematoxylin and eosin, and von Kossa staining for 8 weeks. It was observed that the effect of SIS/PLA scaffolds with GA treatment on bone induction are stronger than PLA scaffolds, that is to say, in the order of PLA/SIS scaffolds with GA treatment > PLA/SIS scaffolds without GA treatment > PGA nonwoven > PLA scaffolds only with GA treatment = PLA scaffolds only without GA treatment for the osteoinduction activity. The possible explanations are (1) many kinds of secreted, circulating, and extracellular matrix-bound growth factors from SIS to significantly affect critical processes of tissue development and differentiation, (2) the exposure of SIS to GA resulted in significantly calcification, and (3) peri-implant fibrosis due to covalent bonding between collagen molecule by crosslinking reaction. In conclusion, it seems that SIS plays an important role for bone induction in SIS/PLA scaffolds for the application of tissue engineering area.

• Biomaterials and Biomechanics in Bioengineering
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• v.1 no.1
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• pp.13-25
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• 2014

In the current study, a drug-eluting stent coated with biodegradable polymers and sirolimus was developed by using an ultrasonic nanocoater and characterized in aspects of surface smoothness and coating thickness. In addition, in vitro release profiles of sirolimus by changing top coating layer with different biodegradable polymers were investigated. Smooth surfaces with variable thickness could be fabricated by optimizing polymer concentration, flow rate, nozzle-tip distance, gas pressure, various solvents and ultrasonic power. Smooth surface could be generated by using volatile solvents (acetone, chloroform, and methylene chloride) or post-treating with solvent vapor. Coating thickness could be controlled by varying injection volume or polymer concentration, and higher concentration could reduce the coating time while obtaining the same thickness. The thickness measurement was the most effectively performed by a conventional cutting method among three different methods that were investigated in this study. Release profiles of sirolimus were effectively controlled by changing polymers for top layer. PLGA made the release rate 3 times faster than PDLLA and PLLA and all top layers prevented burst release at the initial phase of profiles. Our results will provide useful and informative knowledge for developing drug-eluting stents, especially coated with biodegradable polymers.