• Polymer(Korea)
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• v.28 no.4
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• pp.335-343
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• 2004

Carmustine (l,3-bis(2-chloroethyI)-1-nitrosourea, BICNU) used as antineoplastic drug for the treatment of brain tumor is not appropriate for the long term delivery, because it has short biological half life. Therefore, poly(D,L-lactide-co-glycolide) (PLGA) is useful as drug carrier for the long term delivery due to bulk erosion property. Glycolide monomer is applied to release of BICNU owing to non-toxic and monomeric components after biodegradation of PLGA. In this study, BICNU-loaded PLGA wafers with or without glycolide monomer were fabricated by conventional direct compression method for the sustained release of BICNU. These wafers were observed for their release profiles of BICNU and degradation rates by SEM, NMR, and GPC. Furthermore, we make multi-layer wafers and compare them with release profiles of conventional wafer. From these results, drug release of BICNU-loaded PLGA wafers was increased with increasing the glycolid monomer contents. We confirmed that glycolide monomer and BICNU contents in barrier-layer influenced the drug release profiles and degradation rate.

• Polymer(Korea)
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• v.29 no.1
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• pp.69-73
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• 2005

To overcome the main disadvantages of non-viral gene delivery systems such as repeated administration due to the low transfection efficiency, poly(D,L-lactide-co-glycolide) was applied to encapsulate pDNA in its microsphere formulation. Free pDNA or various ratios (w/w) of chitosan/pDNA complexes was used for encapsulation, with the resulting encapsulation efficiency of 44%, 5%, and 8% for free pDNA, 0.7:1 and 1:1 ratios, respectively. Scanning electron micrographs of poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres encapsulating pDNA or chitosan-condensed pDNA revealed a smooth spherical shape immediately after microsphere preparation and a collapsed porous shape in 41 days due to the degradation of PLGA. In vitro release profile showed that the 0.7:1 (w/w) ratio formulation exerted 47% release in 26 days, whereas free pDNA or 1:1 (w/w) ratio formulation did only 15% or 32%, respectively.

• Macromolecular Research
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• v.10 no.5
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• pp.246-252
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• 2002

In order to the development of the delivery device of long-acting local anesthetics for postoperative analgesia and control of chronic pain of cancer patient, fentnyl-loaded poly (L-lactide-co-glycolido) (PLGA, molecular weight, 5,000 g/mole; 50 : 50 mole ratio by lactide to glycolide) microspheres (FMS) were studied. FMS were prepared by an emulsion solvent-evaporation method. The influence of several preparation parameters such as initial drug loading, PLGA concentration, emulsifier concentration, oil phase volume, and fabrication temperature has been investigated on the fentanyl release profiles. Generally, the drug showed the biphasic release patterns, with an initial diffusion followed by a lag period before the onset of the degradation phase, but there was no lag time in our system. Fentanyl was slowly released from FMS over 10 days in vitro with a quasi-zero order property. The release rate increased with increasing drug loading as well as decreasing polymer concentration with relatively small initial burst effect. From the results, FMS may be a good formulation to deliver the anesthetic for the treatment of chronic pain.

• Polymer(Korea)
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• v.26 no.5
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• pp.670-679
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• 2002

1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is one of the effective chemotherapeutic agents which has been used clinically for treating malignant glioma. Poly(D,L-lactide-co-glycolide) (PLGA, molecular weight: 20000 g/mole. mole ratio of lactide to glycolide 75 : 15) is a well known biodegradable polymer used as a drug carrier for drug delivery system. In this study, we investigated the BCNU release behaviour of BCNU-loaded PLGA wafers containing poly (N-vinylpyrrolidone) (PVP) or polyethyleneoxide (PEO) and the effect of hydrophilic polymers incoporated in the wafers. BCNU-loaded PLGA microparticles with or without hydrophilic polymers were prepared by a spray drying method and fabricated into wafers by direct compression. Encapsulation efficiency of BCNU-loaded PLGA microparticles containing PVP and PEO was 85 ∼ 97% and crystallinity of BCNU encapsulated in PLGA decreased significantly initial release amount and release rate of BCNU increased with the increasing PVP or PEO amount. Morphological change and mass loss of wafers during the release test were confirmed that hydration and degradation of PLGA would be facilitated with an increase of hydrophilic polymers.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.712-719
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• 2006

In this study, we prepared core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer with varying graft ratio of PLGA. The synthesis of the DexLG copolymer was confirmed by $^1H$ nuclear magnetic resonance (NMR) spectroscopy. The DexLG copolymer was able to form nanoparticles in water by self-aggregating process, and their particle size was around $50\;nm{\sim}300\;nm$ according to the graft ratio of PLGA. Morphological observations using a transmission electron microscope (TEM) showed that the nanoparticles of the DexLG copolymer have uniformly spherical shapes. From fluorescence probe study using pyrene as a hydrophobic probe, critical association concentration (CAC) values determined from the fluorescence excitation spectra were increased as increase of DS of PLGA. $^1H-NMR$ spectroscopy using $D_2O$ and DMSO approved that DexLG nanoparticles have core-shell structure, i.e. hydrophobic block PLGA consisted inner-core as a drug-incorporating domain and dextran consisted as a hydrated outershell. Drug release rate from DexLG nano-particles became faster in the presence of dextranase in spite of the release rate not being significantly changed at high graft ratio of PLGA. Core-shell type nanoparticles of DexLG copolymer can be used as a colonic drug carrier. In conclusion, size, morphology, and molecular structure of DexLG nanoparticles are available to consider as an oral drug targeting nanoparticles.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.235.1-235.1
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• 2001

• Korean Chemical Engineering Research
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• v.58 no.1
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• pp.36-43
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• 2020

A biliant stent was fabricated using a magnesium alloy wire, a biodegradable metal. In order to control the fast decomposition and corrosion of magnesium alloys in vivo, magnesium alloy wires were coated with biodegradable polymers such as polycaprolactone (PCL), poly(propylene carbonate) (PPC), poly (L-lactic acid) (PLLA), and poly (D, L-lactide-co-glycolide) (PLGA). In the case of PPC, which is a surface erosion polymer, there is no crack or peeling compared to other polymers (PCL, PLLA, and PLGA) that exhibit bulk erosion behavior. Also, the effect of biodegradable polymer coating on the axial force, which is the mechanical property of magnesium alloy stents, was investigated. Stents coated with most biodegradable polymers (PCL, PLLA, PLGA) increased axial forces compared to the uncoated stent, reducing the flexibility of the stent. However, the stent coated with PPC showed the axial force similar to uncoated stent, which did not reduce the flexibility. From the above results, PPC is considered to be the most efficient biodegradable polymer.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.193-200
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• 2010

The objective of this study was to investigate the effects of sample preparation, HPLC conditions and peak measurement methods upon determining progesterone content of poly-d,l-lactide-co-glycolide microspheres. A series of the microspheres with different formulations was first prepared. To determine their actual drug contents, the microspheres were dissolved in tetrahydrofuran and diluted with various amounts of methanol to precipitate the polymer. After removal of polymeric precipitates, the filtrates were subject to HPLC analysis under versatile experimental conditions. Interestingly, the composition of a sample solution (e.g., the ratio of methanol to tetrahydrofuran) affected the magnitudes of both peak fronting and peak broadening of progesterone. Its peak became broader and more asymmetrical at lower methanol:tetrahydrofuran ratios. Furthermore, its peak height was influenced by the proportion of tetrahydrofuran in a sample solution. Such problems encountered with tetrahydrofuran were exacerbated when a larger volume of the sample solution was injected onto an analytical column. Under our experimental conditions a peak area measurement provided more accurate and reliable determination of progesterone content in various microspheres than a peak height determination. Optimizing the composition of a sample solution, HPLC chromatographic conditions and peak analysis methods was a prerequisite to an accurate determination of progesterone encapsulated within microspheres.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.91-94
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• 2011

The purpose of this study was to investigate the effect of peptide charge on the interaction between peptide and poly(D,L-lactide-co-glycolide) (PLGA) for evaluating mechanism of acylated peptide formation in PLGA matrix. As a model peptide, octreotide, a synthetic somatostatin analogue and active ingredient of commercial PLGA product, was used. The disulfide group of octreotide was reduced with dithiothreitol and the sulfhydryl groups were modified with N-${\beta}$-maleimidopropionic acid (BMPA) to neutralize octreotide with positive charge in physiological conditions. The BMPA-conjugated octreotide was identified by measuring the molecular mass with liquid chromatography-mass spectrometry. In the interaction study with PLGA, native octreotide showed initial adsorption to PLGA and substantial production of acylated peptides (56% of overall peptide), whereas BMPA-conjugated octreotide showed minimal adsorption to PLGA and no acylation products for 42 days. Consequently, the neutralization of octreotide completely inhibited the peptide acylation by preventing interaction of peptide with PLGA. In conclusion, this study demonstrates that the initial polymer interaction of peptide is important step for peptide acylation in PLGA matrix and suggests the modulation of peptide charge as strategy for inhibiting the formation of acylated peptide impurities.

• Journal of Pharmaceutical Investigation
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• v.34 no.2
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• pp.101-106
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• 2004

This work aims at examining the cellular uptake behavior of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles derivatized with a protein transduction domain (PTD) using HeLa cells. For this purpose, $Tat_{49-57}$ peptide derived from transcriptional activation (Tat) protein of HIV type-1 was covalently conjugated to the terminal end of PLGA. Nanoparticles were ten prepared with the $Tat_{49-57}-PLGA$ conjugates by a spontaneous phase inversion method. The prepared particles had a mean diameter of ca. 84 nm, as measured by dynamic light scattering. The interaction of the Tat-PLGA nanoparticles with cells was examined by using confocal laser scanning microscopy. It was found tat Tat-PLGA nanoparticles incubated with HeLa cells could efficiently translocate into cytoplasm, while plain PLGA nanoparticles showed negligible cellular uptake. In addition, even at $4^{\circ}C$ or in the presence of sodium azide significant cellular internalization of Tat-PLGA nanoparticles was still observed. These results indicate that a non-endocytotic translocation mechanism might be involved in the cellular uptake of Tat-PLGA nanoparticles.