• Archives of Plastic Surgery
• /
• v.37 no.3
• /
• pp.207-212
• /
• 2010

Purpose: The object of this study is to develop a novel BMP-2 delivery system for continuous osteogenic differentiation and to induce osteogenesis of stem cells using a bi-phase alginate carrier in vitro. Methods: Alginate nanoparticle loaded BMP-2 was prepared by the reverse emulsification-diffusion technique. Physical properties and release profiles of alginate carriers were measured by Instron and ELISA kit, respectively. Cell viability and alkaline phosphate activity of hBMSCs differentiation was also evaluated by MTS and Metra BAP assays, respectively. Results: Optimal concentration for bi-phase alginate carrier was determined as 2 wt% by evaluating mechanical and biological properties, and differentiation of BMSCs for bone regeneration. The 2% bi-phase alginate carrier had the lowest initial and final release ratio. In addition, the 2% bi-phase alginate carrier had a little higher ALP activity than the homogeneous carrier. An improved controlled release profile was obtained by combining alginate hydrogel with lyophilized particles. Conclusion: Bi-phase alginate carrier has many advantages such as biocompatibility and controlled release capability. It is expected to be effective as a scaffold and carrier in bone tissue engineering.

• Journal of Pharmaceutical Investigation
• /
• v.39 no.1
• /
• pp.59-63
• /
• 2009

Soybean phosphatidylcholine microparticles loaded with cyclosporin A (CsA) were prepared by the modified emulsion solvent diffusion and ionic gelation method, in which chitosan on the surface of the microparticles was crosslinked with various concentrations of tripolyphosphate (TPP). The morphology of the particles was characterized by scanning electron microscopy (SEM). The change of particle size and zeta-potential by chitosan on the surface of the lipid microparticles were systematically observed. The encapsulation efficiency and loading capacity of CsA in the particles were determined by high performance liquid chromatography (HPLC). In vitro release kinetics was studied using the dialysis method. In the results, the mean particle size and the zeta-potential of lipid microparticles increased when the attached chitosan was cross-linked (from 2.5 to 6.2 ${\mu}m$ and from -37.0 to +93.0 mV, respectively). The cyclosporin A-loaded lipid microparticles appeared discrete and spherical particles with smooth surfaces. The encapsulation efficiency of CsA was between 79% and 90% while the loading capacity was between 41% and 56%. In vitro release study showed that the crosslinkage of chitosan by TPP significantly delayed the release of CsA from the particles in a concentration-dependent manner. Thus, the release of CsA from the lipid microparticles could be controlled by tripolyphosphate used as a cross-linking agent.

• Bulletin of the Korean Chemical Society
• /
• v.35 no.8
• /
• pp.2391-2399
• /
• 2014

Novel dual responsive pectin hydrogels composed from poly(acrylamidoglycolic acid-co-vinylcaprolactam)/Pectin (PAV-PC) and also PAV-PC hydrogels are used as templates for the production of silver nanoparticles. 5-Fluorouracil is an anticancer drug and has been loaded in situ into PAV-PC hydrogels. Structure and morphology characterization of PAV-PC hydrogels were investigated by fourier transform infrared spectroscopy, differential scanning calorimetry, thermo gravimetric analysis, X-ray diffraction studies, scanning electron microscopy and transmission electron microscopy. The results revealed a molecular level dispersion of the drug in PAV-PC hydrogels. In vitro release of 5-fluorouracil from the PAV-PC hydrogels has been carried out in GIT fluids as well as in various temperatures. 5-Fluorouracil released from PAV-PC hydrogels was 50% at pH 1.2, and 85% at pH 7.4 within 24 h. The release profile was characterized with PAV-PC hydrogels and initial burst effect was significantly reduced in two buffer media (1.2 and 7.4), followed by a continuous and controlled release phase, the drug release mechanism from polymer was due to Fickian diffusion. In situ fabrication of silver nanoparticles inside the hydrogel network via the reduction of sodium borohydrate by PAV-PC chains led to hydrogel nanocomposites. The diameter of the nanocomposites was about 50-100 nm, suitable for uptake within the gastrointestinal tract due to their nanosize range and mucoadhesive properties. These nanocomposite PAV-PC hydrogels showed strong antimicrobial activity towards Bacillus subtilis (G+ve) and Escherichia coli (G-ve).

• Journal of Dairy Science and Biotechnology
• /
• v.23 no.2
• /
• pp.115-123
• /
• 2005

Microcapsules consisting of natural, biodegradable polymers for controlled and/or sustained core release applications are needed. Physicochemical properties of whey proteins suggest that they may be suitable wall materials in developing such microcapsules. The objectives of the research were to develop water-insoluble, whey protein-based microcapsules containing a model water-soluble drug using a chemical cross-linking agent, glutaraldehyde, and to investigate core release from these capsules at simulated physiological conditions. A model water soluble drug, theophylline, was suspended in whey protein isolate (WPI) solution. The suspension was dispersed in a mixture of dichloromethane and hexane containing 1% biomedical polyurethane. Protein matrices were cross-linked with 7.5-30 ml of glutaraldehyde-saturated toluene (GAST) for 1-3 hr. Microcapsules were harvested, washed, dried and analyzed for core retention, microstructure, and core release in enzyme-free simulated gastric fluid (SGF) and simulated intestinal fluid(SIF) at $37^{\circ}C$. A method consisting of double emulsification and heat gelation was also developed to prepare water-insoluble, whey protein-based microcapsules containing anhydrous milkfat (AMF) as a model apolar core. AMF was emulsified into WPI solution (15${\sim}$30%, pH 4.5-7.2) at a proportion of 25${\sim}$50%(w/w, on dry basis). The oil-in-water emulsion was then added and dispersed into corn oil ($50^{\circ}C$) to form an O/W/O double emulsion and then heated at $85^{\circ}C$ for 20 min for gelation of whey protein wall matrix. Effects of emulsion composition and pH on core retention, microstructure, and water-solubility of microcapsules were determined. Overall results suggest that whey proteins can be used in developing microcapsules for controlled and sustained core release applications.

• Biomolecules & Therapeutics
• /
• v.19 no.2
• /
• pp.248-254
• /
• 2011

Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
• /
• 2015.10a
• /
• pp.958-960
• /
• 2015

Sickle cells possess a unique combination of traits that may enable their use as models for novel synthetic tumor targeting controlled release drug carriers with the ability to treat disseminated tumors in advanced metastatic disease. In this study, we assess the ability of light-activated release sickle cells to enhance tumor delivery of the fluorescent dye calcein by delayed photolysis controlled release compared to free systemic administration of calcein. Sickle cells from mouse models of the disease were shown to preferentially accumulate in tumors compared to adjacent tissue, in 4T1 tumors in mice on a time scale about 12 hours. Sickle cells photosensitized with protoporphyrin IX achieved delayed release of 50% of contents 8-16 hours after photoactivation, which was deemed useful for in vivo delivery of cargo to tumors given the tumor accumulation time of the sickle cells. Sickle cells may be useful as a model for new synthetic drug carrier particles with delayed photolysis controlled release properties.

• Transactions of the Korean Society of Mechanical Engineers B
• /
• v.36 no.5
• /
• pp.545-551
• /
• 2012

We investigated the diffusive transport of bupivacaine HCl through the microchannels of microfluidic drug delivery devices. In the biodegradable microfluidic drug delivery devices developed in this research, the drug release rate can be controlled by simply modulating the geometrical parameters of the microchannels, such as the length, number, and cross-sectional area of the microchannels, when the microchannels are used as paths for drug release. However, the hydrophobic nature of a biodegradable polymer, 85/15 poly(lactic-co-glycolic acid), hinders the infiltration of a release medium (phosphate-buffered saline) through the microchannels into the reservoir of a device that contains bupivacaine HCl, at the early stage of drug release. This can have an adverse effect on the early stage release of local analgesic compounds from the device. In this study, microfluidic channels were surface-treated with surfactants such as PEG600 and Tween80, and the effects of the surfactants on the release performance are presented and analyzed.

• KSBB Journal
• /
• v.11 no.6
• /
• pp.676-680
• /
• 1996

The characteristics of controlled drug release were studied for a biodegradable drug delivery system. A biodegradable chitosan matrix was prepared after swelling chitosan with 10%-acetic acid and adding sulfadiazine. The release behavior of sulfadiazine from the chitosan matrix was studied using the Higuchi's diffusion controlled model in phosphate buffer solutions of pH 7.4 and pH 1.2. The drug release time was delayed by increasing the content of sulfadiazine. The drug release at pH 7.4 was more delayed than that at pH 1.2. The reason is that chitosan has greater swelling abilities at low pH than at high pH. The apparent release rate constant(K) increased as the concentration of drug increased. In shoat, the formulation the biodegradable chitosan matrix to suppress the burst effect of drug release mechanism, which led to a sustained release pattern.

• Journal of Pharmaceutical Investigation
• /
• v.26 no.4
• /
• pp.299-308
• /
• 1996

In order to develop the controlled release of a drug from the suppsitories, in vitro drug release and in vivo absorption in rabbits were investigated. Various suppository forms with hollow cavities, into which drugs in the form of fine powder or solid dispersion system(SDS) could be placed, were utilized. The polyvinyl alcohol(PVA) hydrogel as a base, and propranolol HCl(PPH) as a model drug were employed. In vitro drug dissolution studies showed that the dissolved amounts(%) of PPH from PPH-methylcellulose(MC)-SDS and PPH-ethylcellulose(EC)-SDS reached 100% and 63% in 4.5-hours, respectively. In the relative strength test for PVA hydrogel, PVA hydrogel became harder and more rigid when the number of freezing-thawing cycles and the ratio of PVA 2000 were increased. In vitro drug release profile revealed that the release rate(%) of PPH from PPH-EC-SDS and PPH-MC-SDS hollow type suppositories were sustained. The release amount(%) of PPH from PPH-EC-SDS hollow type suppositories was not affected by storage time, but since the use of hydrophilic MC made PPH diffuse into the hydrogel after it absorbed the water of base, the various release patterns were appeared as the storage time went by. In vivo absorption experiments with rabbits showed that PPH-EC-SDS(PPH : EC=1:3) hollow type suppository delayed the absorption of PPH, significantly. The $C_{max}$, $AUC_{0{\rightarrow}8}$ and MRT of PPH powder hollow type suppository were $196.37{\pm}5.63\;ng/ml$, 1105.26 ng/ml/min and 8.66 min, respectively. The $C_{max}$, $AUC_{0{\rightarrow}8}$ and MRT of PPH-EC-SDS(PPH : EC=1:3) were $91.30{\pm]14.14\;ng/ml$, 554.69 ng/ml/min, 235.99 min, respectively.

• YAKHAK HOEJI
• /
• v.47 no.2
• /
• pp.78-84
• /
• 2003

Local anesthetics are used to reduce pain, but they are so frequently injected to patients. So, we prepared lidocaine solid lipid microspheres (SLM) as long acting abdominal injection using spray drying method and evaluated drug entrapment, particle size, SEM, zeta potential and in vitro and in vivo drug release pattern, The particle sizes of SLM were 30∼100$\mu$m and it is enough to inject into abdominal tissue. The entrapment efficiency of SLM was over 95％ as spray drying method. Surfactant and PC decreased the burst effect by 20∼30％. In in vivo test, C-6 showed controlled release concentration profile in plasma for 8 days and C-5 sustained longer than we expected.