Chi-Hwa Wang

Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment.

The effective treatment of malignant brain glioma is hindered by the poor transport across the blood-brain barrier (BBB) and the low penetration across the blood-tumor barrier (BTB). In this study, transferrin-conjugated magnetic silica PLGA nanoparticles (MNP-MSN-PLGA-Tf NPs) were formulated to overcome these barriers. These NPs were loaded with doxorubicin (DOX) and paclitaxel (PTX), and their anti-proliferative effect was evaluated in vitro and in vivo. The in vitro cytotoxicity of drug-loaded NPs was evaluated in U-87 cells. The delivery and the subsequent cellular uptake of drug-loaded NPs could be enhanced by the presence of magnetic field and the usage of Tf as targeting ligand, respectively. In particular, cells treated with DOX-PTX-NPs-Tf with magnetic field showed the highest cytotoxicity as compared to those treated with DOX-PTX-NPs-Tf, DOX-PTX-NPs, DOX-PTX-NPs-Tf with free Tf. The in vivo therapeutic efficacy of drug-loaded NPs was evaluated in intracranial U-87 MG-luc2 xenograft of BALB/c nude mice. In particular, the DOX-PTX-NPs-Tf treatment exhibited the strongest anti-glioma activity as compared to the PTX-NPs-Tf, DOX-NPs-Tf or DOX-PTX-NPs treatment. Mice did not show acute toxicity after administrating with blank MNP-MSN-PLGA-Tf NPs. Overall, MNP-MSN-PLGA-Tf NPs are promising carriers for the delivery of dual drugs for effective treatment of brain glioma.

Double-walled microspheres for the sustained release of a highly water soluble drug: characterization and irradiation studies

Composite double-walled microspheres with biodegradable poly(L-lactic acid) (PLLA) shells and poly(D,L-lactic-co-glycolic acid) (PLGA) cores were fabricated with highly water-soluble etanidazole entrapped within the core as solid crystals. This paper discusses the characterization, in vitro release and the effects of irradiation on this class of microsphere. Through the variation of polymer mass ratios, predictable shell and core dimensions could be fabricated and used to regulate the release rates. A direct and simple method was devised to determine the composition of the shell and core polymer based on the different solubilities of the polymer pair in ethyl acetate. A distribution theory based on solubility parameter explains why highly hydrophilic etanidazole has the tendency to be distributed consistently to the more hydrophilic polymer. Release profiles for normal double-walled samples have about 80% of drug released over 10 days after the initial time lag, while for irradiated double-walled samples, the sustained release lasted for more than 3 weeks. Although sustained release was short of the desired 6-8 weeks required for therapy, a low initial burst of less than 5% and time lags that can be manipulated, allows for administration of these microspheres together with traditional ones to generate pulsatile or new type of releases. The effects of irradiation were also investigated to determine the suitability of these double-walled microspheres as delivery devices to be used in conjunction with radiotherapy. Typical therapeutic dosage of 50 Gy was found to be too mild to have noticeable effects on the polymer and its release profiles, while, sterilization dosages of 25 kGy, lowered the glass transition temperatures and crystalline melting point, indirectly indicating a decrease in molecular weight. This accelerated degradation of the polymer, hence releasing the drug.

Biodegradable microfiber implants delivering paclitaxel for post-surgical chemotherapy against malignant glioma

Paclitaxel-loaded biodegradable implants in the form of microfiber discs and sheets were developed using electrospinning technique and investigated against malignant glioma in vitro and in vivo. The fibrous matrices not only provide greater surface area to volume ratio for effective drug release rates but also give the much needed implantability into tumor resected cavity in post-surgical glioma chemotherapy. Poly-(D,L-lactide-co-glycolide) (PLGA) 85:15 co-polymer was used to fabricate microfiber disc (MFD) and microfiber sheet (MFS) and PLGA 50:50 co-polymer was used to fabricate submicrofiber disc (SFD) and submicrofiber sheet (SFS) to avail different drug release properties. All the dosage forms showed sustained paclitaxel release over 80 days in vitro with a small initial burst. Sheets exhibited a relatively higher initial burst compared to discs probably due to the lower compactness. Also, submicrofibers showed higher release against microfiber due to higher surface area to volume ratio and higher degradation rate. Apoptosis study confirmed the advantage of sustained release of paclitaxel from fiber matrices compared to acute Taxol administration. Animal study confirmed inhibited tumor growth of 75, 78, 69 and 71% for MFD, SFD, MFS and SFS treated groups over placebo control groups after 24 days of tumor growth. Thus these implants may play a crucial role in the local chemotherapy of brain tumors.

Activated carbon derived from carbon residue from biomass gasification and its application for dye adsorption: Kinetics, isotherms and thermodynamic studies

In this work, activated carbon (AC) as an effective and low-cost adsorbent was successfully prepared from carbon residue (or char, one of the by-products from woody biomass gasification) via physical activation. The surface area of char was significantly increased from 172.24 to 776.46m(2)/g after steam activation at 900°C. The obtained activated carbons were then employed for the adsorption of dye (Rhodamine B) and it was found that activated carbon obtained from steam activation exhibited the highest adsorption capability, which is mainly attributed to the higher surface area and the abundance of hydroxyl (-OH) and carboxyl (-COOH) groups on the activated carbon surface. Moreover, it was also found that the adsorption capability significantly increased under the basic condition, which can be attributed to the increased electrostatic interaction between the deprotonated (negatively charged) activated carbon and dye molecules. Furthermore, the equilibrium data were fitted into different adsorption isotherms and found to fit well with Langmuir model (indicating that dye molecules form monolayer coverage on activated carbon) with a maximum monolayer adsorption capability of 189.83mg/g, whereas the adsorption kinetics followed the pseudo-second-order kinetics.

Biocompatibility of electroactive polymers in tissues

The biocompatibility of ethylene-vinyl acetate copolymer (EVAc), polyethylene (PE), and polyaniline (PANi) films in the emeraldine (EM), nigraniline (NA) and leucoemeraldine (LM) intrinsic oxidation states were assessed through subcutaneous implantation into male Sprague-Dawley rats beneath the dorsal skin, for a period ranging from 19 to 90 weeks. Histological examination, interstitial pressure measurement, and X-ray photoelectron spectroscopy (XPS) were employed to determine the biocompatibility of the polymers. The polymers did not provoke inflammatory responses in the subcutaneous tissues over the entire implantation period. Characteristics features associated with tissue-implant incompatibility were not evident near the implantation. Interstitial pressure was measured to evaluate the development of tissue. Low interstitial pressure readings on the region of implantation confirmed the biocompatibility of these polymer types. The surface composition of the electroactive aniline polymers before and after the implantation was characterized by XPS.

Paclitaxel delivery from PLGA foams for controlled release in post-surgical chemotherapy against glioblastoma multiforme.

Paclitaxel loaded biodegradable poly-(DL-lactic-co-glycolic) acid (PLGA) foams with microporous matrix were fabricated by a novel pressure quenching approach to provide a sustained paclitaxel release. The foams with micropores provided increased surface area to volume ratio and were also implantable for post-surgical chemotherapy applications. The two formulations 5% (w/w) paclitaxel loaded PLGA 85:15 foam (F1) and 10% (w/w) paclitaxel loaded PLGA 50:50 foam (F2), were evaluated in vitro and in vivo. Both the foams were found to provide a paclitaxel release beyond a month in vitro with a near zero-order kinetics and with minimum burst release. Furthermore, apoptosis of C6 glioma cells in vitro demonstrated the benefits of sustained paclitaxel release by the foams in comparison to acute Taxol exposure. Both the foams exhibited continuous paclitaxel release in an in vivo (subcutaneous) environment up to a month which correlated well with the in vitro release profiles. Bio-distribution results in the rat brain showed paclitaxel penetration at therapeutic levels up to 3mm into the tissue from the site of foam implantation. Hence these foams could be employed as potential implants for post-surgical chemotherapy against malignant glioma.

BMP-2 plasmid loaded PLGA/HAp composite scaffolds for treatment of bone defects in nude mice

We studied three different types of scaffolds, encapsulating bone morphogenetic protein-2 (BMP-2) plasmid, in terms of their performances in bone regeneration in nude mice. The plasmid was loaded into fibrous matrices in three different ways: coating of naked DNA (Group A) or DNA/chitosan nanoparticles (Group B) onto scaffolds after fiber fabrication by dripping, and encapsulation of DNA/chitosan nanoparticles into scaffold by mixing them with PLGA/DCM solution before fiber fabrication (Group C). Their individual performances were examined by soft X-ray observation, histological analysis and immunostaining of bone tissue. In addition, the BMP-2 protein concentration and alkaline phosphatase (ALP) activity in serum were monitored. The results revealed that the bioactivity of BMP-2 plasmid released from all three kinds of scaffolds was well maintained; this eventually helped improve the healing of segmental defects in vivo. Interestingly, the three kinds of scaffolds released DNA or DNA nanoparticles in different modes and their performances in bone healing were diverse. These observations demonstrate that the in vivo performance of these newly developed DNA delivery devices correlates well with their in vitro release profiles.

The delivery of BCNU to brain tumors.

This paper reports the development of three-dimensional simulations to study the effect of various factors on the delivery of 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to brain tumors. The study yields information on the efficacy of various delivery methods, and the optimal location of polymer implantation. Two types of drug deliveries, namely, systemic administration and controlled release from polymers, were simulated using fluid dynamics analysis package (FIDAP) to predict the temporal and spatial variation of drug distribution. Polymer-based delivery provides higher mean concentration, longer BCNU exposure time and reduced systemic toxicity than bolus injection. Polymer implanted in the core gives higher concentration of drug in both the core and viable zone than the polymer in the viable zone case. The penetration depth of BCNU is very short. This is because BCNU can get drained out of the system before diffusing to any appreciable distance. Since transvascular permeation is the dominant means of BCNU delivery, the interstitial convection has minor effect because of the extremely small transvascular Peclet number. The reaction of BCNU with brain tissues reduces the drug concentration in all regions and its effect increases with rate constant. The implantation of BCNU/ethylene-vinyl acetate copolymer (EVAc) matrix at the lumen of the viable zone immediately following the surgical removal of 80% of the tumor may be an effective treatment for the chemotherapy of brain tumors. The present study provides a quantitative examination on the working principle of Gliadel wafer for the treatment of brain tumors.

Theories of cake filtration and consolidation and implications to sludge dewatering

Abstract This work presents a mini-review of the various theories in previous literature while considering the transport processes in filter cakes during filtration and consolidation. The development of the conventional two-resistance theory (referred to herein as conventional theory) is initially discussed based on different types of power-law constitutive equations. Multi-phase theory is then described, along with the criticisms raised by Willis et al . over the past two decades. Also discussed herein is the validity of some frequently adopted assumptions in filtration studies. Implications of the filtration/consolidation theory to sludge dewatering are finally made.

Electrical capacitance tomography measurements on vertical and inclined pneumatic conveying of granular solids

Abstract Pneumatic conveying of granular solids in vertical and inclined risers was studied using electrical capacitance tomography (ECT). The focus of the study was on flow development past a smooth bend connecting the riser to a horizontal duct which brought the gas-particle mixture to the riser. In the vertical riser, dispersed flow manifested a core–annular structure, whose development is discussed. Three different time-dependent flow patterns were imaged. Slugging flow, which appeared to be intrinsic to riser flow, took the form of alternating bands of core–annular disperse flow and a slug with a particle-rich core. Averaging over these two structures yielded a composite distribution with high particle concentration both at the axis and the wall region. Pulsing flow, whose ECT fingerprint was similar to that of slugging flow, was largely an entrance effect. Stationary and moving annular capsules with a dilute core were also observed, and such flow patterns do not appear to have been reported previously. Our ECT measurements probing the development of disperse flow in an inclined riser past a bend revealed that the particle loading initially decreased, subsequently increased and then leveled off. Regimes such as eroding dune flow and flow over a settled layer could be easily imaged using ECT. The surface of the settled layer had a concave shape, suggesting that the particles were picked up from the settled layer by airflow at the center and deposited on the sides of the tube.