Preparation of Biodegradable and Elastic Poly(ε-caprolactone-co-lactide) Copolymers and Evaluation as a Localized and Sustained Drug Delivery Carrier.

To develop a biodegradable polymer possessing elasticity and flexibility, we synthesized MPEG-b-(PCL-co-PLA) copolymers (PCxLyA), which display specific rates of flexibility and elasticity. We synthesize the PCxLyA copolymers by ring-opening polymerization of ε-caprolactone and l-lactide. PCxLyA copolymers of various compositions were synthesized with 500,000 molecular weight. The PCxLyA copolymers mechanical properties were dependent on the mole ratio of the ε-caprolactone and l-lactide components. Cyclic tensile tests were carried out to investigate the resistance to creep of PCxLyA specimens after up to 20 deformation cycles to 50% elongation. After in vivo implantation, the PCxLyA implants exhibited biocompatibility, and gradually biodegraded over an eight-week experimental period. Immunohistochemical characterization showed that the PCxLyA implants provoked in vivo inflammation, which gradually decreased over time. The copolymer was used as a drug carrier for locally implantable drugs, the hydrophobic drug dexamethasone (Dex), and the water-soluble drug dexamethasone 21-phosphate disodium salt (Dex(p)). We monitored drug-loaded PCxLyA films for in vitro and in vivo drug release over 40 days and observed real-time sustained release of near-infrared (NIR) fluorescence over an extended period from hydrophobic IR-780- and hydrophilic IR-783-loaded PCxLyA implanted in live animals. Finally, we confirmed that PCxLyA films are usable as biodegradable, elastic drug carriers.

Cellular behavior of human adipose-derived stem cells on wettable gradient polyethylene surfaces.

Appropriate surface wettability and roughness of biomaterials is an important factor in cell attachment and proliferation. In this study, we investigated the correlation between surface wettability and roughness, and biological response in human adipose-derived stem cells (hADSCs). We prepared wettable and rough gradient polyethylene (PE) surfaces by increasing the power of a radio frequency corona discharge apparatus with knife-type electrodes over a moving sample bed. The PE changed gradually from hydrophobic and smooth surfaces to hydrophilic (water contact angle, 90° to ~ 50°) and rough (80 to ~120 nm) surfaces as the power increased. We found that hADSCs adhered better to highly hydrophilic and rough surfaces and showed broadly stretched morphology compared with that on hydrophobic and smooth surfaces. The proliferation of hADSCs on hydrophilic and rough surfaces was also higher than that on hydrophobic and smooth surfaces. Furthermore, integrin beta 1 gene expression, an indicator of attachment, and heat shock protein 70 gene expression were high on hydrophobic and smooth surfaces. These results indicate that the cellular behavior of hADSCs on gradient surface depends on surface properties, wettability and roughness.

Preparation and evaluation of injectable microsphere formulation for longer sustained release of donepezil.

In this study, donepezil-loaded PLGA and PLA microspheres (Dp-PLGA-M/Dp-PLA-M) and Dp-PLA-M wrapped in a polyethylene glycol-b-polycaprolactone (PC) hydrogel (Dp-PLA-M/PC) were prepared to reduce the dosing frequency of injections to treat Alzheimer's disease patients. Dp-PLGA-M and Dp-PLA-M with a uniform particle size distribution were repeatably fabricated in nearly quantitative yield and with high encapsulated Dp yields using an ultrasonic atomizer. The injectability and in vitro and in vivo Dp release, biodegradation, and inflammatory response elicited by the Dp-PLGA-M, Dp-PLA-M, and Dp-PLA-M/PC formulations were then compared. All injectable formulations showed good injectability with ease of injection, even flow, and no clogging using a syringe needle under 21-G. The injections required a force of <1 N. According to the biodegradation rate of micro-CT, GPC and NMR analyses, the biodegradation of Dp-PLA-M was slower than that of Dp-PLGA-M, and the biodegradation rate of Dp-PLA-M/PC was also slower. In the Dp release experiment, Dp-PLA-M sustained Dp for longer compared with Dp-PLGA-M. Dp-PLA-M/PC exhibited a longer sustained release pattern of two months. In vivo bioavailability of Dp-PLA-M/PC was almost 1.4 times higher than that of Dp-PLA-M and 1.9 times higher than that of Dp-PLGA-M. The variations in the Dp release patterns of Dp-PLGA-M and Dp-PLA-M were explained by differences in the degradation rates of PLGA and PLA. The sustained release of Dp by Dp-PLA-M/PC was attributed to the fact that the PC hydrogel served as a wrapping matrix for Dp-PLA-M, which could slow down the biodegradation of PLA-M, thus delaying the release of Dp from Dp-PLA-M. Dp-PLGA-M induced a higher inflammatory response compared to Dp-PLA-M/PC, suggesting that the rapid degradation of PLGA triggered a strong inflammatory response. In conclusion, Dp-PLA-M/PC is a promising injectable Dp formulation that could be used to reduce the dosing frequency of Dp injections.

Enhanced intra-articular therapy for rheumatoid arthritis using click-crosslinked hyaluronic acid hydrogels loaded with toll-like receptor antagonizing peptides.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that results in the deterioration of joint cartilage and bone. Toll-like receptor 4 (TLR4) has been pinpointed as a key factor in RA-related inflammation. While Toll-like receptor antagonizing peptide 2 (TAP2) holds potential as an anti-inflammatory agent, its in vivo degradation rate hinders its efficacy. We engineered depots of TAP2 encapsulated in click-crosslinked hyaluronic acid (TAP2+Cx-HA) for intra-articular administration, aiming to enhance the effectiveness of TAP2 as an anti-inflammatory agent within the joint cavity. Our data demonstrated that FI-TAP2+Cx-HA achieves a longer retention time in the joint cavity compared to FI-TAP2 alone. Mechanistically, we found that TAP2 interacts with TLR4 on the cell membranes of inflammatory cells, thereby inhibiting the nuclear translocation of NF-κB and maintaining it in an inactive cytoplasmic state. In a rat model of RA, the TAP2+Cx-HA formulation effectively downregulated the inflammatory cytokines TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This led to a more rapid restoration of cartilage thickness, increased deposition of glycosaminoglycans, and new bone tissue formation in the regenerated cartilage, in comparison to a single TAP2 treatment after a six-week period. Our results suggest that TAP2+Cx-HA could serve as a potent intra-articular treatment for RA, offering both symptomatic relief and promoting cartilage regeneration. This innovative delivery system holds significant promise for improving the management of RA and other inflammatory joint conditions. STATEMENT OF SIGNIFICANCE: In this study, we developed a therapy by creating toll-like receptor 4 (TLR4)-antagonizing peptide (TAP2)-loaded click-crosslinked hyaluronic acid (TAP2+Cx-HA) depots for direct intra-articular injection. Our study demonstrates that FI-TAP2+Cx-HA exhibits a more than threefold longer lifetime in the joint cavity compared to FI-TAP2 alone. Furthermore, we found that TAP2 binds to TLR4 and masks the nuclear localization signals of NF-κB, leading to its sequestration in an inactive state in the cytoplasm. In a rat model of RA, TAP2+Cx-HA effectively suppresses inflammatory molecules, specifically TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This resulted in faster regeneration of cartilage thickness, increased glycosaminoglycan deposits in the regenerated cartilage, and a twofold increase in new bone tissue formation compared to a single TAP2 treatment.

An injectable cationic hydrogel electrostatically interacted with BMP2 to enhance in vivo osteogenic differentiation of human turbinate mesenchymal stem cells.

We have designed and characterized an injectable, electrostatically bonded, in situ-forming hydrogel system consisting of a cationic polyelectrolyte [(methoxy)polyethylene glycol-b-(poly(ε-caprolactone)-ran-poly(L-lactic acid)] (MP) copolymer derivatized with an amine group (MP-NH2) and anionic BMP2. To the best of our knowledge, there have been hardly any studies that have investigated electrostatically bonded, in situ-forming hydrogel systems consisting of MP-NH2 and BMP2, with respect to how they promote in vivo osteogenic differentiation of human turbinate mesenchymal stem cells (hTMSCs). Injectable formulations almost immediately formed an electrostatically loaded hydrogel depot containing BMP2, upon injection into mice. The hydrogel features and stability of BMP2 inside the hydrogel were significantly affected by the electrostatic attraction between BMP2 and MP-NH2. Additionally, the time BMP2 spent inside the hydrogel depot was prolonged in vivo, as evidenced by in vivo near-infrared fluorescence imaging. Biocompatibility was demonstrated by the fact that hTMSCs survived in vivo, even after 8 weeks and even though relatively few macrophages were in the hydrogel depot. The osteogenic capacity of the electrostatically loaded hydrogel implants containing BMP2 was higher than that of a hydrogel that was simply loaded with BMP2, as evidenced by Alizarin Red S, von Kossa, and hematoxylin and eosin staining as well as osteonectin, osteopontin, osteocalcin, and type 1α collagen mRNA expression. The results confirmed that our injectable, in situ-forming hydrogel system, electrostatically loaded with BMP2, can enhance in vivo osteogenic differentiation of hTMSCs.

Polyethyleneimine-mediated gene delivery into human adipose derived stem cells.

In this study, we examined the use of polyethyleneimine (PEI) as a carrier for gene delivery in human adipose tissue-derived stem cells (hADSCs). These multipotent cells can form bone, cartilage, adipose, and other connective tissues. In primary culture, hADSCs are fibroblastic in appearance in primary culture, and they show a high rate of proliferation for at least five passages. Immunophenotyping showed that these cells are positive for the mesenchymal stem cell markers CD29 and CD44 but negative for the hematopoietic cell surface markers CD34, CD45, and c-kit. PEI and Lipofectamine were compared as gene carriers for hADSCs. DNA completely bound PEI at a negative-to-positive (N/P) charge ratio of 4. The PEI-DNA complexes were spherical with smooth surfaces. As the proportion of PEI was increased, the size of the PEI-DNA complexes decreased from 990 to 130nm, the positive surface charge decreased, and the cytotoxicity increased. Flow cytometry revealed that the transfection efficiency using PEI at N/P charge ratios of 4 and 8 was higher than that of Lipofectamine. The highest transfection efficiency (19%) was obtained at an N/P charge ratio of 8. After transfection, the enhanced green fluorescent protein (EGFP) started to localize in the nuclei of hADSCs at 4h 30m and localize over cytoplasm from 9h 30m. In conclusion, PEI acts as an effective gene carrier for hADSCs.

The osteogenic differentiation of rat muscle-derived stem cells in vivo within in situ-forming chitosan scaffolds.

We herein examined the bone formation from rat muscle-derived stem cells (rMDSCs) using an injectable in situ-forming chitosan gel in vivo. The rMDSCs were easily isolated from rat muscle tissue. The osteogenic factors caused differentiation of rMDSCs toward the osteogenic lineage. The rMDSCs survived well on the scaffold created by the in vitro and in vivo in situ-forming chitosan gel, indicating that in situ gel-forming chitosan was a suitable substrate for the attachment and proliferation of rMDSCs. Bone formation was observed only in chitosan gel containing both rMDSCs and osteogenic factors. Subcutaneous implantation of the in situ-forming chitosan gel demonstrated that rMDSCs-containing chitosan gel induced much lower host tissue responses than did the chitosan gel alone, probably due to the immunosuppression of the transplanted rMDSCs.

Bone regeneration by means of a three-dimensional printed scaffold in a rat cranial defect.

Recently, computer-designed three-dimensional (3D) printing techniques have emerged as an active research area with almost unlimited possibilities. In this study, we used a computer-designed 3D scaffold to drive new bone formation in a bone defect. Poly-L-lactide (PLLA) and bioactive ß-tricalcium phosphate (TCP) were simply mixed to prepare ink. PLLA + TCP showed good printability from the micronozzle and solidification within few seconds, indicating that it was indeed printable ink for layer-by-layer printing. In the images, TCP on the surface of (and/or inside) PLLA in the printed PLLA + TCP scaffold looked dispersed. MG-63 cells (human osteoblastoma) adhered to and proliferated well on the printed PLLA + TCP scaffold. To assess new bone formation in vivo, the printed PLLA + TCP scaffold was implanted into a full-thickness cranial bone defect in rats. The new bone formation was monitored by microcomputed tomography and histological analysis of the in vivo PLLA + TCP scaffold with or without MG-63 cells. The bone defect was gradually spontaneously replaced with new bone tissues when we used both bioactive TCP and MG-63 cells in the PLLA scaffold. Bone formation driven by the PLLA + TCP30 scaffold with MG-63 cells was significantly greater than that in other experimental groups. Furthermore, the PLLA + TCP scaffold gradually degraded and matched well the extent of the gradual new bone formation on microcomputed tomography. In conclusion, the printed PLLA + TCP scaffold effectively supports new bone formation in a cranial bone defect.

An in vivo study of the host tissue response to subcutaneous implantation of PLGA- and/or porcine small intestinal submucosa-based scaffolds.

An innate immune response is often found at the site of biomaterial implantation. Since the effective use of biomaterials in vivo requires good biocompatibility and biofunctionality, it is vital that we assess and compare the inflammatory reactions provoked by various implanted biomaterials in vivo. In the present study, we assessed the host tissue response to poly(lactic-co-glycolic acid) (PLGA)- and small intestinal submucosa (SIS)-based scaffolds subcutaneously implanted in Fischer rats. Our results revealed that the PLGA-based scaffolds resulted in severe post-implantation inflammation, whereas the SIS-based scaffolds induced only a slight post-implantation inflammation and a PLGA/SIS-based copolymer yielded intermediate results.

Repair of diaphyseal bone defects with calcitriol-loaded PLGA scaffolds and marrow stromal cells.

Calcitriol (1,25(OH)2D3)-loaded porous poly(D,L-lactide-co-glycolide) (PLGA) scaffolds prepared by solvent casting/salt leaching method were used to repair a 1.5 cm diaphyseal segmental bone defect as a fully absorbable osteogenic biomaterial. The in vitro release of sulforhodamine B (SRB) from PLGA scaffold was measured using spectrophotometer, considering SRB as a model drug. The SRB released from SRB-incorporated PLGA scaffold during 3 months was with relatively low initial burst. The calcitriol-loaded PLGA scaffolds with or without marrow stromal cells (MSCs) were implanted in a critical-sized intercalated bone defect in rabbit femur. Defects were assessed by radiographs until 9 weeks. The bony union of the defect was observed only in the calcitriol-loaded groups. RT-PCR results indicated that MSCs, which were seeded into calcitriol-loaded scaffold, expressed an increased level of alkaline phosphatase, osteonectin, and type I collagen mRNA at day 10. After 2 and 4 weeks, the implanted scaffolds were evaluated by histology. New osteoid matrix and direct calcium deposits were more evident in calcitriol/PLGA/MSC group. Three-dimensional computed tomography and frontal tomographic images of repaired femur showed that normal femur anatomy had been restored with cortical bone with no implanted PLGA remnants at 20 weeks. It can be concluded that the porous calcitriol-loaded PLGA scaffold combined with MSCs may be a novel method for repairing the large loaded bone defect.

Adhesion behavior of human bone marrow stromal cells on differentially wettable polymer surfaces.

An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. In this study, we investigated how human bone marrow stromal cells (hBMSCs) respond to scaffold substrates. We prepared wettable polymer surfaces by exposing polymer sheets to radio frequency plasma discharge, which gradually oxidizes the polymer surface, increasing the roughness and greatly reducing the hydrophobicity. We found that hBMSCs adhered better to highly hydrophilic and rough surfaces than to hydrophobic and smooth surfaces. In addition, the cells flattened extensively on hydrophilic surfaces. Further, c-fos gene expression increased in parallel with the degree of hydrophilicity, whereas the expression of the c-myc gene was higher on hydrophobic than on hydrophilic surfaces. Finally, p53 gene expression was higher on more hydrophobic or hydrophilic surfaces than on moderately hydrophobic or hydrophilic surfaces. These results indicate that the biological signals induced by cell adhesion depend on the wettability of the surface to which the cells attach.

Porcine small intestinal submucosa sheets as a scaffold for human bone marrow stem cells.

Native small intestinal submucosa (SIS) sheet was prepared by removal of inside and outside layer of porcine jejunum. The acid treated SIS sheet was also prepared by dipping of native SIS sheet in acetic acid solution. The native or acid treated SIS sheets exhibited elastic and soft property on touch. The surface of native SIS sheet appears to be covered with thin and long collagen fibers entangled into networks. The fibers and fibrils at acid treated SIS sheet disappeared due to the acidic erosion of collagen fiber. The water uptake of acid treated SIS sheet (1300%) was higher than that of the native SIS sheet (500%). The cell morphology and proliferation of human bone marrow stem cells (hBMSCs) on SIS sheet was examined. The hBMSCs on the SIS sheet showed a flattened morphology, while cells in the polyglycolic acid (PGA) mesh showed rounded cell morphology. The cell viability on native or acid treated SIS sheet was higher than that of PGA mesh. The hBMSCs in both native and acid treated SIS sheet were grown at a similar rate. The number of adhering hBMSCs increased with incubation time. Thus, we could confirm that native or acid treated SIS sheet could act as a potential scaffold to enhance the hBMSCs proliferation by providing probably natural environments.

In vivo osteogenic differentiation of rat bone marrow stromal cells in thermosensitive MPEG-PCL diblock copolymer gels.

Methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL) diblock copolymers were prepared by ring-opening polymerization and their phase transition behavior characterized as a function of temperature. The MPEG-PCL solutions formed a sol at room temperature, and underwent sol-to-gel followed by gel-to-sol phase transitions as the temperature was increased. The temperature range over which the solutions were in a gel state could be extended simply by increasing the PCL chain length in the diblock copolymer. Scanning electron microscopy (SEM) images of MPEG-PCL solutions in the sol and gel states revealed near-regular and irregular porous structures, respectively. in vitro culture of rat bone marrow stromal cells (rBMSCs) on gel surfaces exhibited mostly round cells after 1 day of incubation. SEM images of the attached cells clearly showed the cell body and anchoring filopodia. Injection of room-temperature diblock copolymer solutions into Sprague-Dawley rats produced a gel at body temperature. In situ gel-forming scaffolds in vivo were successfully fabricated by simple subcutaneous injection of MPEG-PCL diblock copolymer solutions. The gel implants retained their original shape for 4 weeks without in- flammation at the injection site. Gel implants removed after 4 weeks were found to be surrounded by a thin fibrous capsule consisting of fibroblasts and blood vessels cells. Hematoxylin and eosin (H&E) and von Kossa staining revealed bone formation in gel implants containing both rBMSCs and dexamethasone, with the degree of bone formation increasing markedly with increasing dexamethasone concentration. Thus, our results show that in situ gel scaffolds fabricated from MPEG-PCL diblock copolymer solutions containing dexamethasone enable multipotent rBMSCs to produce viable bone when injected into rats.

Preparation and magnetic resonance imaging effect of polyvinylpyrrolidone-coated iron oxide nanoparticles.

Polyvinylpyrrolidone (PVP)-coated iron oxide nanoparticles were prepared by the thermal decomposition of Fe(CO)(5) (iron pentacarbonyl) in one step. X-ray diffraction (XRD), transmission electron microscopy (TEM), electrophoretic light scattering (ELS), infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) together with the variation of the molar ratio of PVP/Fe(CO)(5), solvent, and molecular weight of PVP, were used to characterize the PVP-coated iron oxide nanoparticles. Fifty to hundred nanometer-sized iron oxide nanoclusters with a spherical shape were formed in dimethylformamide (DMF), used as a solvent, and exhibited an enhanced stability in the aqueous media. Their magnetic properties were investigated by superconducting quantum interface device (SQUID). The in vitro cytotoxicity test revealed that the PVP-coated iron oxide nanoparticles exhibited excellent biocompatibility by MTT assay. Magnetic resonance imaging (MRI) effect was observed with the administration of PVP-coated iron oxide nanoparticles through the marginal vein of rabbit, resulting in improved detection of the liver lesions.

Evaluation of in vitro and in vivo antitumor activity of BCNU-loaded PLGA wafer against 9L gliosarcoma.

The purpose of the present study was to develop implantable BCNU-loaded poly(D,L-lactide-co-glycolide) (PLGA) wafer for the controlled release of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and to evaluate its in vitro and in vivo antitumor activity. The release rate of BCNU from PLGA wafer increased with the increase of BCNU amount loaded and the release was continued until 7 days. In vitro and in vivo antitumor activity of BCNU-loaded PLGA wafer was investigated using in vitro cytotoxicity against 9L gliosarcoma cells and a subcutaneous (s.c.) solid tumor model of 9L gliosarcoma, respectively. The wafers containing BCNU showed more effective cytotoxicity than BCNU powder due to its short half-life and inhibited the proliferation of 9L gliosarcoma cells. BCNU-loaded PLGA wafer delayed the growth of the tumors significantly and increasing the dose of BCNU in the wafer resulted in a substantial regression of the tumor. These results of antitumor activity of BCNU-loaded PLGA wafer demonstrate the feasibility of the wafers for clinical application.

Sustained release of bovine serum albumin using implantable wafers prepared by MPEG-PLGA diblock copolymers.

MPEG-PLGA diblock copolymers, consisting of methoxy polyethylene glycol (MPEG) and poly(L-lactic-co-glycolic acid) (PLGA), were synthesized by ring-opening polymerization of L-lactide and glycolide in the presence of MPEG as an initiator. Implantable wafers, using diblock copolymers as a drug carrier, were fabricated by direct compression method after freeze milling of the diblock copolymers and bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) as a model protein drug. The wafers prepared with MPEG-PLGA diblock copolymers exhibited initial burst in the release of BSA. The BSA release profiles from the wafers depended on MPEG-PLGA diblock copolymer compositions. The in vitro release of the BSA also correlated with the degradation rate of the PLGA part in the diblock polymers. The wafers prepared from diblock copolymers with an increased MPEG segment showed the more structural metamorphosis of crack form due to higher water absorption of MPEG inside the wafer, and induced faster BSA release. The wafers prepared by using MPEG-PLGA diblock copolymers in the presence of small intestinal submucosa (SIS) as a drug carrier additive exhibited controlled BSA release profiles, although the wafers exhibited release patterns with a lag time at the initial stage as the MPEG segment in diblock copolymer compositions increased. Thus, we confirmed that the MPEG-PLGA diblock copolymers could be used as a protein delivery carrier in implantable wafer form.

Enhancement of the stability of BCNU using self-emulsifying drug delivery systems (SEDDS) and in vitro antitumor activity of self-emulsified BCNU-loaded PLGA wafer.

The main purpose of this study was to develop self-emulsifying drug delivery systems (SEDDS) for the improvement of the stability of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) after released from poly (D,L-lactide-co-glycolide) (PLGA) wafer and to evaluate its in vitro antitumor activity against 9L gliosarcoma cells. The in vitro stability test of BCNU was characterized by the BCNU amount in phosphate buffered saline (PBS, pH 7.4) at 37 degrees C. SEDDS increased in vitro half-life of BCNU up to 130 min compared to 45 min of intact BCNU. Self-emulsified (SE) BCNU was fabricated into wafers with flat and smooth surface by compression molding. In vitro release of BCNU from SE BCNU-loaded PLGA wafer was prolonged up to 7 days followed first order release kinetics. Beside, the cytotoxicity of SE BCNU-loaded PLGA wafer against 9L gliosarcoma cells was higher than intact BCNU-loaded PLGA wafer which is more susceptible to hydrolysis. SE BCNU degraded much more slowly than the intact BCNU in PLGA matrix at 25 degrees C. These results strongly suggest that the self-emulsion system increased the stability of BCNU after released from PLGA wafer. From these results, it could be expected that the penetration depth of BCNU could be improved in brain tissue using self-emulsion system.

Preparation of porcine small intestinal submucosa sponge and their application as a wound dressing in full-thickness skin defect of rat.

Small intestinal submucosa (SIS) sponge was prepared by crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The prepared SIS sponges exhibited elastic and soft property on touch and were ease to handle. The SIS sponges have the pore diameter of 100-200 microm and an interconnective porous structure. The SIS sponges exhibited high water absorption ability over 8000%. The water uptake of SIS sponges decreased as SIS concentration used to manufacture SIS sponge increased. In wound healing test, SIS sponge attained uniform adherence to the wound surface. The SIS sponges absorbed higher extent of exudation for wound than that covered with Tegaderm as control. Wound area contracted above 80% at the 21st postoperative day. The SIS sponge treated wound was almost completely covered with a thin layer of epidermis at 4 weeks. In addition, the dermal collagen in the wound regenerated at only SIS sponges treated wounds. The progress of granulous tissue formation was faster in SIS sponges as wound dressing than in Tegaderm. In conclusion, we found that the SIS sponges might be a potential material as a wound dressing.

Synthesis and characterization of polyanhydride for local BCNU delivery carriers.

p-Carboxyphenoxy propane (CPP) prepolymer consisting of 4 units and sebacic acid (SA) prepolymer consisting of about 10 units were synthesized by reacting CPP and SA in the presence of excess acetic anhydride, respectively. Polyanhydride, poly(CPP-SA) copolymers were copolymerized by a melt polycondensation process with a mixture of CPP and SA prepolymer. Copolymers of average molecular weight up to 110,000 g/mol were achieved. The crystallinity of poly(CPP-SA) copolymers was decreased by the addition of the CPP homopolymer segment to SA homopolymer. Poly(CPP-SA) copolymers gradually degraded for period of 10 days. No large difference of weight loss observed according to molecular weight variation of poly(CPP-SA) copolymers. BCNU release from wafers fabricated by poly(CPP-SA) showed a sustained release pattern with no initial burst and delay of drug release.

Characterization of degradation behavior for PLGA in various pH condition by simple liquid chromatography method.

The aim of this study was to detect the amount of lactic acid (LA) and glycolic acid (GA) in poly(D,L-lactide-co-glycolide) (PLGA) by development a simple HPLC method and to determine the pH of media, which can influence on degradation of PLGA and drug release. Analysis of in vitro degradation behavior of PLGA with two different molecular weights as 8000 and 33,000 g/mol were performed in various media conditions (pH 3.0, 5.0, 7.0, and 9.0 of PBS and distilled water (approx. pH 5.8)). Also, effect of some additives on PLGA degradation was also investigated in pH 7.0 of PBS. GA and LA were easily detected by a simple HPLC method (retention time: 6.5 min and 10.2 min, respectively). The result showed that GA was released larger amount than that of LA considering the initial sample weight of polymers, due to the higher hydrophilic property. In the lower pH of media conditions, the PLGA was faster degraded generally. The presence of various additives, moreover, affected decrease of pH and slight acceleration of LA and GA detection.