• Macromolecular Research
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• v.14 no.5
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• pp.573-578
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• 2006

Three different, polymer-platinum conjugates (hydrogels, microparticles, and nanoparticles) were synthesized by complexation of cis-dichlorodiammineplatinum(II) (cisplatin) with partially succinylated glycol chitbsan (PSGC). Succinic anhydride was used as a linker to introduce cisplatin to glycol chitosan (GC). Succinylation of GC was investigated systematically as a function of the molar ratio of succinic anhydride to glucosamine, the methanol content in the reaction media, and the reaction temperature. By controlling the reaction conditions, water-soluble, partially water-soluble, and hydrogel-forming PSGCs were synthesized, and then conjugated with cisplatin. The complexation of cisplatin with water-soluble PSGC via a ligand exchange reaction of platinum from chloride to the carboxylates induced the formation of nano-sized aggregates in aqueous media. The hydrodynamic diameters of PSGC/cisplatin complex nano-aggregates, as determined by light scattering, were 180-300 nm and the critical aggregation concentrations (CACs), as determined by a fluorescence technique using pyrene as a probe, were $20-30{\mu}g/mL$. The conjugation of cisplatin with partially water-soluble PSGC, i.e., borderline between water-soluble and water-insoluble PSGC, produced micro-sized particles $<500{\mu}m$. Cisplatin-complexed PSGC hydrogels were prepared from water-insoluble PSGCs. All of the cisplatin-incorporated, polymer matrices released platinum in a sustained manner without any significant initial burst, suggesting that they may all be useful as slow release systems for cisplatin. The release rate of platinum increased with the morphology changes from hydrogel through microparticle to nanoparticle systems.

• Macromolecular Research
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• v.11 no.5
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• pp.334-340
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• 2003

In order to fabricate new sustained delivery device of nerve growth factor (NGF), we developed NGF-loaded biodegradable poly(L-lactide-co-glycolide) (PLGA, the mole ratio of lactide to glycolide 75:25, molecular weight: 83,000 and 43,000 g/mole, respectively) film by novel and simple sandwich solvent casting method for the possibility of the application of neural tissue engineering. PLGA was copolymerized by direct condensation reaction and the molecular weight was controlled by reaction time. Released behavior of NGF from NGF-loaded films was characterized by enzyme linked immunosorbent assay (ELISA) and degradation characteristics were observed by scanning electron microscopy (SEM) and gel permeation chromatography (GPC). The bioactivity of released NGF was identified using a rat pheochromocytoma (PC-12) cell based bioassay. The release of NGF from the NGF-loaded PLGA films was prolonged over 35 days with zero-order rate of 0.5-0.8 ng NGF/day without initial burst and could be controlled by the variations of molecular weight and NGF loading amount. After 7 days NGF released in phosphate buffered saline and PC-12 cell cultured on the NGF-loaded PLGA film for 3 days. The released NGF stimulated neurite sprouting in cultured PC-12 cells, that is to say, the remained NGF in the NGF/PLGA film at 37 $^{\circ}C$ for 7 days was still bioactive. This study suggested that NGF-loaded PLGA sandwich film is released the desired period in delivery system and useful neuronal growth culture as nerve contact guidance tube for the application of neural tissue engineering.

• Macromolecular Research
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• v.13 no.4
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• pp.285-292
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• 2005

We developed alginate beads loaded with transforming growth $factor-{\beta}_{1}(TGF-{\beta}_{1})$ to examine the possible application of the scaffold and cytokine carrier in tissue engineering. In this study, bone marrow stromal cells (BMSCs) and $TGF{\beta}_{1}$ were uniformly encapsulated in the alginate beads and then cultured in vitro. The cell morphology and shape of the alginate beads were observed using inverted microscope, scanning electron microscope (SEM), histological staining and RT-PCR to confirm chondrogenic differentiation. The amount of the $TGF{\beta}_{1}$ released from the $TGF-{\beta}_{1}$ loaded alginate beads was analyzed for 28 days in vitro in a phosphate buffered saline (pH 7.4) at $37^{\circ}C$. We observed the release profile of $TGF-{\beta}_{1}$ from $TGF-{\beta}_{1}$ loaded alginate beads with a sustained release pattern for 35 days. Microscopic observation showed the open cell pore structure and abundant cells with a round morphology in the alginate beads. In addition, histology and RT-PCR results revealed the evidence of chondrogenic differentiation in the beads. In conclusion, these results confirmed that $TGF-{\beta}_{1}$ loaded alginate beads provide excellent conditions for chondrogenic differentiation.

• Applied Chemistry for Engineering
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• v.16 no.6
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• pp.790-793
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• 2005

Recently, the interest in the extension of human life and personal health has been increased. Accordingly, many researchers in a pharmacy and a medical world have been making efforts to improve the sustained drug release property and the stability of drug release property in a body. Many biological researches have demonstrated that chitosan derivatives are effective, safe absorption enhancers that can improve the delivery efficiency of drug and vaccine, and they are suitable for controlled drug release because they have good stability, bio-compatibility, and biodegradability. In this study the experiment was performed in vivo by utilizing chitosan nanoparticles as a biopolymer to control drug delivery rate at an optimal temperature, pH, and concentration. It was observed that nanoparticles containing insulin could effectively control the blood glucose at a low level.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.78.1-78.13
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• 2022

Background: Florfenicol might be ineffective for treating Staphylococcus aureus small colony variants (SCVs) mastitis. Objectives: In this study, florfenicol-loaded chitosan (CS)-sodium tripolyphosphate (TPP) composite nanogels were prepared to allow targeted delivery to SCV infected sites. Methods: The formulation screening, the characteristics, in vitro release, antibacterial activity, therapeutic efficacy, and biosafety of the florfenicol composite nanogels were studied. Results: The optimized formulation was obtained when the CS and TPP were 10 and 5 mg/mL, respectively. The encapsulation efficiency, loading capacity, size, polydispersity index, and zeta potential of the optimized florfenicol composite nanogels were 87.3% ± 2.7%, 5.8% ± 1.4%, 280.3 ± 1.5 nm, 0.15 ± 0.03, and 36.3 ± 1.4 mv, respectively. Optical and scanning electron microscopy showed that spherical particles with a relatively uniform distribution and drugs might be incorporated in cross-linked polymeric networks. The in vitro release study showed that the florfenicol composite nanogels exhibited a biphasic pattern with the sustained release of 72.2% ± 1.8% at 48 h in pH 5.5 phosphate-buffered saline. The minimal inhibitory concentrations of commercial florfenicol solution and florfenicol composite nanogels against SCVs were 1 and 0.25 ㎍/mL, respectively. The time-killing curves and live-dead bacterial staining showed that the florfenicol composite nanogels were concentration-dependent. Furthermore, the florfenicol composite nanogels displayed good therapeutic efficacy against SCVs mastitis. Biological safety studies showed that the florfenicol composite nanogels might be a biocompatible preparation because of their non-toxic effects on the renal tissue and liver. Conclusions: Florfenicol composite nanogels might improve the treatment of SCV infections.

• Polymer(Korea)
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• v.34 no.3
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• pp.269-273
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• 2010

The primary objective of this work is to find the optimal condition for the granule tablet formulation of alfuzosin-HCl that aims to achieve a sustained drug release. (Hydroxypropyl)methyl cellulose (HPMC) is one of the most widely used polymer as a drug formulation and therefore has been utilized in this study as an excipient. Alfuzosin-HCl granule tablet was developed using the various viscosities of HPMC and the effects of viscosity on drug release was investigated. Fourier transform-infrared (FTIR) and X-ray diffraction (XRD) were employed to investigate the chemical structure and crystallization of alfuzosin-HCl in the formulation. We prepared the granule tablet by a direct compression method and studied the release profile in the stimulated intestinal fluid (pH 6.8). As the viscosity of HPMC increased the release of alfuzosin-HCl decreased, demonstrating that controlled release of alfuzosin-HCl can be achieved by varying the viscosity of HPMC.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.511-519
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• 1993

The short and variabke transit of drug throught GI tracj and the inter-and intra-subject variations of the transit restrict the sustained drug absorption after oral adminstration. These restrictions may be solved by retaining the dosage forms in the stomach. Then the dosage form will act as a platform which releases the drug slowly and makes the GI absorption occur for a long time. In this study, as the platforms, PVP hydrogels were synthesized by chemical and y-irradiation method in the cylindrical test tube. The chemical method means the synthesis of the hydrogel by heating the mixed solution of N-vinyl-2-pyrrolidone [monomer], acrylated albumin [crosslinking agent], 2, 2'-agobis(2-methylpropionitrile) [initiator] and proxyphylline [drug] at $65^{\circ}C$ for 5 hr. The $\gamma$-irradiation method means the synthesis of the hydrogel by irradiation with $^{60}$ Co $\gamma$-ray of the mixed solution of the monomer, acrylated albumin, and flurbiprofen [drug] at room temperature with total 0.2 Mrad for 3 hr. Our intention is to design the hydrogel tablet (diameter : 1.20 cm, thickness : 0.60 cm) which swells in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the period of drug release. After releasing drug, the hydrogel should be degraded by the enzymeatic digestion in the stomach, or by hydrolysis and eventually solubilized. Thus, in votro tests were performed to examine the factors that affect swelling and drug release from the PVP hydrogels. Experimental results show that the hydrogels swell to a size larger than the diameter of the pylorus(l.3$\pm$0.7 cm) and the hydrogel prepared by the chemical method is digested by pepsin. But the hydrogel prepared by the $\gamma$-irradiation method was not digested by the pepsin and just collapsed with time. Thus, the swelling of the hydrogel synthesized by $\gamma$-irradiation was independent albumin acrylation time and pepsin concentration. But drug content and radiation dose affected the swelling and drug release kinetics of the hydrogel. Drug release from the hydrigels was prolonged up to about 24 hr. Therefore, it was concluded that by adjusting these factors, the albumin-crosslinked PVP hydrogel synthesized by $\gamma$-irradiation method is expected to be retained in the stomach for up to 60hr and be a potential platform of drugs for long-term GI absorption.

• Polymer(Korea)
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• v.31 no.3
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• pp.189-193
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• 2007

We developed the doxorubicin-loaded PLGA double-layered microspheres using relatively simple oil-in-water (O/W) solvent evaporation method for sustained release of doxorubicin and investigated the release behavior according to PLGA molecular weight and initial drug loading. The double-layered microsphere was characterized on the surface, the cross-section morphology, the behavior of doxorubicin release for 5 weeks by SEM and fluorescence spectrophotometer. Double-layered microspheres showed smooth surfaces and clear difference between core and outer-shell. As the PLGA molecular weight increased, the release rate of doxorubicin-loaded, double-layered microspheres decreased. These results showed that the release behaviors can be controlled by the variation of molecular weight of PLGA.

• Polymer(Korea)
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• v.38 no.5
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• pp.656-663
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• 2014

Atorvastatin calcium-loaded polyoxalate (POX) microspheres were prepared by an emulsion solvent-evaporation/ extraction method of oil-in-oil-in-water ($O_1/O_2/W$) for sustained release. We investigated the release behavior according to initial drug ratio, molecular weight ($M_w$) and concentration of POX and concentration of emulsifier. The microsphere was characterized on the surface, the cross-section morphology and the behavior of atorvastatin calcium release for 10 days by scanning electron microscopy (SEM) and high performance liquid chromatography (HPLC). The analysis of crystallization was analyzed to use X-ray diffraction (XRD), differential scanning calorimeter (DSC) and Fourier transform infrared (FTIR). These results showed that the release behaviors can be controlled by preparation conditions.

• Parasites, Hosts and Diseases
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• v.44 no.4 s.140
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• pp.361-366
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• 2006

Sustained-releasing praziquantel (SRP) tablet was designed for single dose treatment regimen of clonorchiasis. A previous pre-clinical study confirmed its sustained-releasing characteristics and a better cure rate than conventional praziquantel (PZQ). In this clinical study, the pharmacokinetics of this SRP tablet were investigated in human volunteers (phase 1; 12 volunteers), and its curative efficacy was examined in clonorchiasis patients (phase 2; 20 volunteers). In the phase 1 clinical study, blood concentrations of both tablets showed wide individual variation. The $AUC_{last}$ of SRP was $497.9{\pm}519.0ng{\cdot}hr/ml\;(mean{\pm}SD)$ and PZQ of $628.6{\pm}695.5\;ng{\cdot}hr/ml$, and the $AUC_{inf}$ of SRP was $776.0{\pm}538.5\;ng{\cdot}hr/ml$ and of PZQ $658.6{\pm}709.9\;ng{\cdot}hr/ml$. $C_{max}$ values of SRP and PZQ were $90.7{\pm}82.2ng/ml\;and\;214.9{\pm}251.9\;ng/ml$, and $T_{max}$ values were $3.42{\pm}1.43\;hr\;and\;1.96{\pm}1.23\;hr$, respectively. SRP tablets showed similar AUC values, but lower $C_{max}$ and longer $T_{max}$ values than PZQ. In the phase 2 study, SRP at 30 mg/kg (single dose) achieved a 60% cure rate and a 95.5% egg reduction rate. The cure rate of a single dose SRP was unsatisfactory compared with that of the conventional PZQ dose, but much better than that achieved by a single dose PZQ.