• 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.

• 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.

• 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.

• 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.

• Polymer(Korea)
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• v.26 no.1
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• pp.128-138
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• 2002

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU, Carmustine)-loaded poly(D, L-lactide-co-glycolide) (PLGA, lactide/glycolide mole ratio 75 : 25) microparticles were prepared and fabricated into wafers in an attempt to study the possibility for the treatment of malignant glioma by direct inserting the wafers to the tumor or the cavity remained after surgical resection of the tumor. SEM observation of the microparticles prepared by spray drying method revealed that the microparticles were spherical, i. e. microspheres. Significant reduction of the crystallinity of BCNU encapsulated in PLGA was confirmed by X-ray diffraction and differential scanning calorimetry analyses of the BCNU-loaded PLGA microparticles. Release pattern of BCNU was dependent on several preparation parameters, such as the molecular weight and concentration of PLGA, and initial BCNU loading amount, etc. In vitro release of BCNU was prolonged over 8 weeks with close to zero-order release pattern after initial burst effect. Observations of morphological change of wafers and pH change of release media during release test period confirmed that hydration and degradation of PLGA would be facilitated with an increase of BCNU-loading amount.

• Polymer(Korea)
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• v.24 no.5
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• pp.728-735
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• 2000

Fentanyl-loaded biodegradable poly(L-lactide-co-glycolide) (75 : 25 by mole ratio of lactide to glycolide, PLGA) microspheres (MSs) were prepared to study the possibility for long-acting local anesthesia. We developed the fentanyl base (FB, slightly water-soluble)-loaded PLGA MSs by means of conventional O/W solvent evaporation method. The size of MSs was in the range of 10~150 ${\mu}{\textrm}{m}$. The morphology of MSs was characterized by SEM, and the in vitro release amounts of FB were analyzed by HPLC. The lowest porous cross-sectional morphology and the highest encapsulation efficiency were obtained by using gelatin as an emulsifier. The influences of several preparation parameters, such as emulsifier types, molecular weights and concentrations of PLGA, and initial drug loading amount, etc., have been observed in the release patterns of FB. The release of FB in vitro was more prolonged over 25 days, with close to zero-order pattern by controlling the preparation parameters. We also investigated the physicochemical properties of FB-loaded PLGA MSs by X-ray diffraction and differential scanning calorimeter.

• 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.

• 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.