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Biomedical subjects

Hua Ai

Publications and source records attributed to Hua Ai.

16 recordsLinked to original sources
PubMed2007

Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods.

The purpose of this study was to evaluate the antitumor efficacy and local drug distribution from doxorubicin-containing poly(D,L-lactide-co-glycolide) (PLGA) implants for intratumoral treatment of liver cancer in a rabbit model. Cylindrical polymer millirods (length 8 mm, diameter 1.5 mm) were produced using 65% PLGA, 21.5% NaCl, and 13.5% doxorubicin. These implants were placed in the center of VX2 liver tumors (n = 16, 8 mm in diameter) in rabbits. Tumors were removed 4 and 8 days after millirod implantation, and antitumor efficacy was assessed using tumor size measurements, tumor histology, and fluorescent measurement of drug distribution. The treated tumors were smaller than the untreated controls on both day 4 (0.17 +/- 0.06 vs. 0.31 +/- 0.08 cm(2), p = 0.048) and day 8 (0.14 +/- 0.04 vs. 1.8 +/- 0.8 cm(2), p = 0.025). Drug distribution profiles demonstrated high doxorubicin concentrations (>1000 microg/g) at the tumor core at both time points and drug penetration distances of 2.8 and 1.3 mm on day 4 and 8, respectively. Histological examination confirmed necrosis throughout the tumor tissue. Biodegradable polymer millirods successfully treated the primary tumor mass by providing high doxorubicin concentrations to the tumor tissue over an eight day period.

Absorbable Implants↗
PubMed2006

Amplification of the antigen-antibody interaction from quartz crystal microbalance immunosensors via back-filling immobilization of nanogold on biorecognition surface.

A new quartz crystal microbalance immunoassay method based on a novel transparent immunoaffinity reactor was developed for clinical immunoassay. To construct such an affinity reactor, resonators with a frequency of 10 MHz were fabricated by affinity binding of functionalized gold nanoparticles (nanogold) to quartz crystal with immobilized specific ligand for the label-free analysis of the affinity reaction between a ligand and its receptor. [Recombinant human tumor markers, carcinoembryonic antigen (CEA) was chosen as a model ligand.] The binding of target molecules onto the immobilized antibodies decreased the sensor's resonant frequency, and the frequency shift was proportional to the CEA concentration in the range of 3.0-50 ng/ml with a detection limit of 1.5 ng/ml at a signal/noise ration of 3. A glycine-HCl solution (pH 2.3) was used to release antigen-antibody complexes from the biorecognition surface. Good reusability was exhibited. Moreover, spiking various levels of CEA into normal human sera was diagnosed using the proposed immunoassay. Analytical results show the precision of the developed immunoassay is acceptable, implying a promising alternative approach for detecting CEA in clinical immunoassay. Compared with the conventional enzyme-linked immunosorbent assay, the proposed immunoassay system was simple and rapid without multiple labeling and separation steps. Importantly, the proposed immunoassay system could be further developed for the immobilization of other antigens or biocompounds.

Antibodies↗
PubMed2006

Modulating beta-lapachone release from polymer millirods through cyclodextrin complexation.

Beta-lapachone (beta-lap) is a novel anticancer agent that kills tumors overexpressing the NADPH: quinone oxidoreductase enzyme. However, poor aqueous solubility and low bioavailability hinder its therapeutic applications. Herein we describe the development of poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods for local delivery of beta-lap. The objective was to investigate the use of beta-lap inclusion complexes with cyclodextrins (CDs) to control beta-lap release kinetics from PLGA millirods. Differential scanning calorimetry was performed to measure drug/polymer interactions, complexation efficiency with different CDs, and complex/polymer interactions. beta-Lap was found to have a solid-state solubility of 13% in PLGA. beta-Lap dissolution in PLGA matrix lowered the glass transition temperature of PLGA from 44 to 31 degrees C, and led to a slow release of beta-lap (8.8+/-1.2% release after 22 days). For beta-lap and CD interactions, increasing complexation efficiency was observed in the order of alpha-CD, gamma-CD, and beta-CD. beta-Lap complexation with hydroxypropyl-beta-cyclodextrin (HPbeta-CD) prevented drug dissolution in PLGA, and led to fast release (79.6+/-2.1% after 2 days). Sustained drug release was achieved when beta-lap was complexed with alpha-CD or gamma-CD. These data demonstrate the ability to tailor beta-lap release kinetics via CD complexation, providing exciting opportunities for the use of beta-lap-millirods for intratumoral drug delivery.

Antineoplastic Agents↗
PubMed2006

Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems.

We describe the development of multifunctional polymeric micelles with cancer-targeting capability via alpha(v)beta(3) integrins, controlled drug delivery, and efficient magnetic resonance imaging (MRI) contrast characteristics. Doxorubicin and a cluster of superparamagnetic iron oxide (SPIO) nanoparticles were loaded successfully inside the micelle core. The presence of cRGD on the micelle surface resulted in the cancer-targeted delivery to alpha(v)beta(3)-expressing tumor cells. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI imaging and alpha(v)beta(3)-specific cytotoxic response of these multifunctional polymeric micelles.

Cell Line, Tumor↗
PubMed2005

Interactions between self-assembled polyelectrolyte shells and tumor cells.

Layer-by-layer self-assembled polyelectrolyte shells are a new class of micro/nanocapsules with unique physicochemical properties for potential applications in drug/gene delivery. The objective of this study was to investigate the interactions of polyelectrolyte shells ( approximately 1 mum in diameter) with MCF-7 breast cancer cells and identify key parameters that affect such interactions. Tailoring of surface properties of polyelectrolyte shells was achieved by choosing different outermost layer materials, including cationic polymers, anionic polymers, and lipid bilayers. Different surface compositions led to a wide range of electrostatic potentials from -46 to +47 mV in phophate-buffered saline buffer. Confocal microscopy studies showed that the polyelectrolyte shells were internalized into the cell cytoplasm, but not into the nuclei. Correlation of cell uptake with shell surface compositions was complicated by the adsorption of serum proteins on the surface of polyelectrolyte shells, particularly polycation-coated shells. To prevent protein adsorption, poly(ethylene glycol) (PEG) grafted poly(ethyleneimine) (PEI) copolymers (1:1, 1:5, 1:10 graft ratios) were synthesized and introduced on the shell surface. Shells coated with PEI-PEG copolymers effectively reduced protein adsorption whereas PEI-PEG copolymers with lower graft ratios achieved higher cell uptake efficiency after 24 h of incubation with MCF-7 cells.

Biocompatible Materials↗
PubMed2004

Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery.

Diblock copolymers of poly(epsilon-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 microg ml(-1), while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 degrees C demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.

Antibiotics, Antineoplastic↗
PubMed2003

Biocompatibility of layer-by-layer self-assembled nanofilm on silicone rubber for neurons.

Electrostatic layer-by-layer (LbL) self-assembly, a novel method for ultrathin film coating has been applied to silicone rubber to encourage nerve cell adhesion. The surfaces studied consisted of precursor layers, with alternating cationic poly(ethyleneimine) (PEI) and anionic sodium poly(styrenesulfonate) (PSS) followed by alternating laminin and poly-D-lysine (PDL) layers or fibronectin and PDL layers. Film growth increased linearly with the number of layers. Every fibronectin/PDL and laminin/PDL bilayer was 4.4 and 3.5 nm thick, respectively. All layers were more hydrophilic than the unmodified silicone rubber surface, as determined from contact angle measurements. Of the coatings studied, a PDL layer was the most hydrophilic. A multilayer film with composition [PSS/PEI]3+[fibronectin/PDL]4 or [PSS/PEI]3+[laminin/PDL]4 was highly favorable for neuron adhesion, in contrast to bare silicone rubber substrate. The film coated on silicone rubber is biocompatible for cerebellar neurons with active viability, as shown by lactate dehydrogenase (LDH) assay and fluorescence cellular metabolism observations. These results demonstrate that LbL self-assembly provides an effective approach to apply films with nanometer thickness to silicone rubber. Such only few nanometer thick films are biocompatible with neurons, and may be used to coat devises for long-term implant in the central nervous system.

Animals↗
PubMed2003

Disruption of microtubules in rat skeletal muscle does not inhibit insulin- or contraction-stimulated glucose transport.

Insulin and muscle contractions stimulate glucose transport in skeletal muscle through a translocation of intracellular GLUT4 glucose transporters to the cell surface. Judged by immunofluorescence microscopy, part of the GLUT4 storage sites is associated with the extensive microtubule cytoskeleton found in all muscle fibers. Here, we test whether microtubules are required mediators of the effect of insulin and contractions. In three different incubated rat muscles with distinct fiber type composition, depolymerization of microtubules with colchicine for < or =8 h did not inhibit insulin- or contraction-stimulated 2-deoxyglucose transport or force production. On the contrary, colchicine at least partially prevented the approximately 30% decrease in insulin-stimulated transport that specifically developed during 8 h of incubation in soleus muscle but not in flexor digitorum brevis or epitrochlearis muscles. In contrast, nocodazole, another microtubule-disrupting drug, rapidly and dose dependently blocked insulin- and contraction-stimulated glucose transport. A similar discrepancy between colchicine and nocodazole was also found in their ability to block glucose transport in muscle giant "ghost" vesicles. This suggests that the ability of insulin and contractions to stimulate glucose transport in muscle does not require an intact microtubule network and that nocodazole inhibits glucose transport independently of its microtubule-disrupting effect.

Animals↗
PubMed2003

Nano-encapsulation of furosemide microcrystals for controlled drug release.

Furosemide microcrystals were encapsulated with polyions and gelatin to control the release of the drug in aqueous solutions. Charged linear polyions and gelatin were alternatively deposited on 5-microm drug microcrystals through layer-by-layer (LbL) assembly. Sequential layers of poly(dimethyldiallyl ammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) were followed by adsorption of two to six gelatin/PSS bilayers with corresponding capsule wall thicknesses ranging from 45 to 115 nm. The release of furosemide from the coated microparticles was measured in aqueous solutions of pH 1.4 and 7.4. At both pH values, the release rate of furosemide from the encapsulated particles was reduced by 50-300 times (for capsules coated with two to six bilayers) compared to uncoated furosemide. The results provide a method of achieving prolonged drug release through self-assembly of polymeric shells on drug microcrystals.

Crystallization↗
PubMed2003

Coating and selective deposition of nanofilm on silicone rubber for cell adhesion and growth.

A recently developed method for surface modification, layer-by-layer (LbL) assembly, has been applied to silicone, and its ability to encourage endothelial cell growth and control cell growth patterns has been examined. The surfaces studied consisted of a precursor, with alternating cationic polyethyleneimine (PEI) and anionic sodium polystyrene sulfonate (PSS) layers followed by alternating gelatin and poly-D-lysine (PDL) layers. Film growth increased linearly with the number of layers. Each PSS/PEI bilayer was 3 nm thick, and each gelatin/PDL bilayer was 5 nm thick. All layers were more hydrophilic than the unmodified silicone rubber surface, as determined from contact angle measurements. The contact angle was primarily dictated by the outermost layer. Of the coatings studied, gelatin was the most hydrophilic. A film of (PSS/PEI)4/(gelatin/PDL)4/ gelatin was highly favorable for cell adhesion and growth, in contrast to films of (PSS/PEI)8 or (PSS/PEI)8/PSS. Cell growth patterns were successfully controlled by selective deposition of microspheres on silicone rubber, using microcontact printing with a silicone stamp. Cell adhesion was confined to the region of microsphere deposition. These results demonstrate that the LbL self-assembly technique provides a general approach to coat and selectively deposit films with nanometer thickness on silicone rubber. Furthermore, they show that this method is a viable technique for controlling cellular adhesion and growth.

Animals↗
PubMed2003

Biomedical applications of electrostatic layer-by-layer nano-assembly of polymers, enzymes, and nanoparticles.

The introduction of electrostatic layer-by-layer (LbL) self-assembly has shown broad biomedical applications in thin film coating, micropatterning, nanobioreactors, artificial cells, and drug delivery systems. Multiple assembly polyelectrolytes and proteins are based on electrostatic interaction between oppositely charged layers. The film architecture is precisely designed and can be controlled to 1-nm precision with a range from 5 to 1000 nm. Thin films can be deposited on any surface including many widely used biomaterials. Microencapsulation of micro/nanotemplates with multilayers enabled cell surface modification, controlled drug release, hollow shell formation, and nanobioreactors. Both in vitro and in vivo studies indicate potential applications in biology, pharmaceutics, medicine, and other biomedical areas.

Biomimetic Materials↗
PubMed2002

The role of photoperiod and temperature in determination of summer and winter diapause in the cabbage beetle, Colaphellus bowringi (Coleoptera: Chrysomelidae).

The cabbage beetle, Colaphellus bowringi, is a short-day species undergoing an imaginal summer and winter diapause. Its photoperiodic response highly depends on temperature. All adults entered diapause at </= 20 degrees C regardless of photoperiods. High temperatures strongly weakened the diapause-inducing effects of long daylengths. The diapause-averting influence of short daylengths was expressed only at high temperatures (above 20 degrees C). This indicates that the beetle has a cryptic ability to reproduce in summer. In fact, summer and winter diapause were induced principally by relatively low temperatures in the field, whereas photoperiod had less influence on diapause induction. The critical daylength for the autumnal population was between 12 h and 13 h. By transferring from a long day to a short day or vice versa at different times after hatching, it was shown that the sensitive stage with regard to photoperiod was the larva, whereas a long day was photoperiodically more potent than a short day. The sensitive stage to temperature encompassed the larval, pupal and adult stages. This different response pattern serves to ensure that the beetle enters summer and winter diapause in time. The selections for non-diapause trait under laboratory (at 25 degrees C) and natural conditions (at >24 degrees C) showed that the beetle could lose its sensitivity to photoperiod very rapidly.

Journal Article↗
PubMed2002

Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle.

AMP-activated protein kinase (AMPK) may mediate the stimulatory effect of contraction and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on glucose transport in skeletal muscle. In muscles with different fiber type composition from fasted rats, AICAR increased 2-deoxyglucose transport and total AMPK activity approximately twofold in epitrochlearis (EPI), less in flexor digitorum brevis, and not at all in soleus muscles. Contraction increased both transport and AMPK activity more than AICAR did. In EPI muscles, the effects of AICAR and contractions on glucose transport were partially additive despite a lower AMPK activity with AICAR compared with contraction alone. In EPI from fed rats, glucose transport responses were smaller than what was seen in fasted rats, and AICAR did not increase transport despite an increase in AMPK activity. AICAR and contraction activated both alpha(1)- and alpha(2)-isoforms of AMPK. Expression of both isoforms varied with fiber types, and alpha(2) was highly expressed in nuclei. In conclusion, AICAR-stimulated glucose transport varies with muscle fiber type and nutritional state. AMPK is unlikely to be the sole mediator of contraction-stimulated glucose transport.

AMP-Activated Protein Kinases↗
PubMed2002

Gelatin-glutaraldehyde cross-linking on silicone rubber to increase endothelial cell adhesion and growth.

Silicone is a biomaterial that is widely used in many areas because of its high optical clarity, its durability, and the ease with which it can be cast. However, these advantages are counterbalanced by strong hydrophobicity. Gelatin cross-linking has been used as a hydrophilic coating on many biomaterials but not on silicone rubber. In this study, two gelatin glutaraldehyde (GA) cross-linking methods were used to coat a hydrophilic membrane on silicone rubber. In method I, gelatin and GA were mixed in three different proportions (64:1, 128:1, and 256:1) before coating. In method II, a newly formed 5% gelatin membrane was cross-linked with a 2.5% GA solution. All coatings were hydrophilic, as determined from the measurement of contact angle for a drop of water on the surface. Bovine coronary arterial endothelial cells were shown to grow well on the surface modified by method II at 72 h. In method I, the cells grew well for gelatin-GA proportions of 64:1 and 128:1 at 72 h. No cell attachment on untreated silicone rubber was observed by the third d of seeding. The results indicated that both methods of gelatin-GA cross-linking provided a hydrophilic surface on silicone for endothelial cell adhesion and growth in vitro.

Animals↗
PubMedDate not supplied

Electrostatic layer-by-layer nanoassembly on biological microtemplates: platelets.

Platelets were coated with 78-nm silica nanoparticles, 45-nm fluorescent nanospheres, or bovine immunoglobulin G (IgG) through layer-by-layer assembly by alternate adsorption with oppositely charged linear polyions. Sequential deposition on platelet surfaces of cationic poly(dimethyldiallylammonium chloride) and anionic poly(styrene sulfonate) was followed by adsorption of nanoparticles or immunoglobulins. Nano-organized shells of platelets were demonstrated by transmission electron microscopy and fluorescence microscope images. Bovine IgG was assembled on platelets, as verified with anti-bovine IgG-FITC labeling. Localized targeting of anti-IgG shelled platelets was also demonstrated. An ability to coat blood cells with nano-organized shells can have applications in cardiovascular research and targeted drug delivery.

Adsorption↗