• Macromolecular Research
• /
• v.11 no.5
• /
• pp.352-356
• /
• 2003

The objectives of this study were to investigate the influence of gamma irradiation for sterilization on poly(D,L-lactide-co-glycolide) (PLGA) with different molecular weight and the effect of gamma irradiation on the release behavior of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) from PLGA wafer with various irradiation doses. The effect of gamma irradiation on PLGA was evaluated by gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and electron paramagnetic resonance (EPR). The weight average molecular weight (M$_{w}$) and glass transition temperature (T$_{g}$) of PLGA decreased after gamma irradiation. The extent of M$_{w}$ reduction was dependent on irradiation dose and PLGA molecular weight. Using EPR spectroscopy, we successfully detected gamma irradiation induced free radicals in PLGA. The gamma irradiation increased the release rate of BCNU from PLGA wafer at applied irradiation doses except 2.5 Mrad of irradiation dose in this study.study.

• Macromolecular Research
• /
• v.11 no.3
• /
• pp.183-188
• /
• 2003

The controlled delivery of anticancer agents using biodegradable polymeric implant has been developed to solve the problem of penetration of blood brain barrier and severe systemic toxicity. This study was performed to prepare 5-FU-loaded poly (L-lactide-co-glycolide) (PLGA) wafer fabricated microparticles prepared by two different method and to evaluate their release profile for the application of the treatment of brain tumor. 5-FU-loaded PLGA microparticles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC). SEM observation of the 5-FU-loaded PLGA microparticles prepared by rotary solvent evaporation method showed that 5-FU was almost surrounded by PLGA and significant reduction of crystallinity of 5-FU was confirmed by XRD. In case of release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by mechanical mixing, the release profile of 5-FU followed near first order release kinetics. In contrast to the above result, release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by rotary solvent evaporation method followed near zero order release kinetics. These results indicate that preparation method of the 5-FU-loaded PLGA microparticles to fabricate into wafers was contributed to drug release profile.

• Polymer(Korea)
• /
• v.28 no.4
• /
• pp.335-343
• /
• 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)
• /
• v.31 no.5
• /
• pp.447-453
• /
• 2007

In this study, we fabricated recrystallized PLGA (rPLGA) particles using the vacuum drying method. In order to investigate an applicability of the rPLGA particles for controlled release system of 5-fluorouracil (5-FU) loaded PLGA wafer, we prepared three different wafers using; 1) untreated PLGA (uPLGA), 2) rPLGA, and 3) uPLGA and rPLGA (4 : 1, 1 : 1 or 1 : 4). The rPLGA particles were characterized using NMR, IR and GPC to compare with uPLGA particles. The surface and cross section morphology of the prepared wafers were observed by the scanning electron microscope. The release profile of the 5-FU loaded wafer was measured by HPLC. The 5-FU/rPLGA wafer released the incorporated 5-FU in a sustained manner with low initial burst compared to 5-FU/uPLGA. These results showed that the ratio of pure PLGA/recrystallized PLGA can affect the release behaviors.

• Polymer(Korea)
• /
• v.26 no.5
• /
• pp.680-690
• /
• 2002

Implantable biodegradable wafers were prepared with pamidronate -loaded poly (L-lactide-co-glycolide) (PLGA, 75 : 25 mole ratio by lactide to glycolide, molecular weight : 20000 and 90000 g/mole) by direct compression method for the sustained release of pamidronate to investigate the possibility for the treatment of bone resorption. Pamidronate-loaded PLGA powders were prepared by means of physical mixing and spray drying with the control of formulation factors and characterized by scanning electron microscope and X-ray diffractometer. The pamidronate-loaded PLGA powders fabricated into wafers by direct compression under the constant pressure and time at room temperature. These wafers were also observed for their structural characteristic, release pattern, and degradation pattern. The release rate of pamidronate increased with increasing their initial loading ratio as well as increasing wafer thickness. The molecular weight of PLGA affects the release pattern : the higher molecular weight of PLGA, the faster release rate. It can be explained that the higher viscosity of high molecular PLGA solution at same concentration tends to aggregate PLGA and pamidronate resulting in unstable pharmaceutical dosage form. This system had advantages in terms of simplicity in design and obviousness of drug release rate and nay be useful as an implantable dosage form for the treatment of aural cholesteatoma.

• Polymer(Korea)
• /
• v.25 no.6
• /
• pp.884-892
• /
• 2001

Biodegradable wafers were prepared with poly (L-lactide-co-glycolide) (50 : 50 mole ratio of lactide to glycolide, molecular weight:5000 g/mole) by direct compression method for the sustained release of nifedipine to investigate the possibility of the treatment of hypertension. PLGA wafers were prepared by altering initial drug/polymer loading ratio, wafer thickness, and hydroxypropyl methylcellulose (HPMC) content. These wafers showed new zero-order release patterns for 11 days, and various biphasic release patterns could be obtained by altering the composition of wafers such as addition of matrix binder as HPMC to the PLGA wafer to reduce release rate of initial phase. The onset of polymer mass loss only occured after 4 days and about 40% of mass loss was observed after 11 days nifedipine release. This system had advantages in terms of simplicity in design and obviousness of drug release rate and may be useful as an implantable dosage form.

• Korean Chemical Engineering Research
• /
• v.46 no.2
• /
• pp.205-210
• /
• 2008

Poly(D,L-lactide-co-glycolide) (PLGA) has been widely used as carriers in controlled release delivery systems due to its biodegradability and relatively good biocompatibility. However, Release pattern of carriers fabricated using PLGA have disadvantage an initial burst within a few days, lag time several days and then sudden release changes. To solve these problems of PLGA, we fabricated PLGA wafer including monomer. Also, drug release behavior restraint sudden burst effect using recrystallization of PLGA. Recrystallized PLGA was characterized the morphological difference by SEM and in vitro release behavior measured by HPLC. The PLGA molecular weight analyzed to recognize monomer influence during degradation process of polymer using GPC. In this study, drug release duration cut short up to three days and was eliminated the lag time based on the bulk erosion.

• Polymer(Korea)
• /
• v.31 no.3
• /
• pp.201-205
• /
• 2007

Biodegradable polymers such as polylactide, polyglycolide and poly (lactide- co-glycolide) (PLGA) have been extensively investigated because of easily controlled drug release rate, completely degradable materials without the toxic by-product, and good biocompatibility. But, according to the bulk erosion property of PLGA in vitro test, it had the disadvantage that first-order release reduced releasing amount slowly after excessive initial burst. In this study we used PLGA powder obtained through recrystallization to revise bulk erosion property of PLGA. The PLGA used in this study was prepared by vacuum drying method and to estimate release profiles of BCNU loaded PLGA wafer. We also evaluated the release profile of drug with the water soluble additive. It was found that the drug loaded PLGA recrystallized by vacuum drying method exhibited the initial burst and the constant rate of drug release compared to that prepared by a conventional method.

• Polymer(Korea)
• /
• v.26 no.5
• /
• pp.670-679
• /
• 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)
• /
• v.28 no.4
• /
• pp.328-334
• /
• 2004

A series of methoxy poly(ethylene glycol) (MPEG)-poly(L-lactide-co-glycolide) (PLGA) diblock copolymers were synthesized by ring-opening polymerization of L-lactide and glycolide with carbitol (134 g/mole) or different molecular weights of MPEG (550, 2000, and 5000 g/mole) as an initiator in presence of Sn(Oct)$_2$. The properties of diblock copolymers were characterized by using $^1$H-NMR, GPC, and XRD. After uniform mixing of block copolymers and 1% albumin bovine-fluorescein isothiocyanate(FITC-BSA) with a freeze miller, the wafers loaded FITC-BSA were fabricated by using a mold with a dimensions of 3 mm${\times}$1mm diameter. The release profiles of FITC-BSA and the pH changes of wafer were examined using pH 7.4 PBS for 30 days at 37$^{\circ}C$. The release profiles of albumin showed fast initial burst as the molecular weights of MPEG increased. As a result of this study, the release behavior of BSA was controlled with introducing MPEG in the block copolymers.