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At least 433 records · Page 24Linked to original sources
PubMed1997

Use of an automated fluorescent microsphere method to measure regional blood flow in the fetal lamb.

We have developed a method for measuring regional blood flow by means of fluorescent microspheres in all organs and tissues of the fetal lamb, including brain, heart, lung, liver, gut, spleen, kidney, adrenal, brown fat, skin, muscle, bone, and placenta. Five different fluorescent-labeled microspheres were used: blue (B), yellow-green (Y), orange (O), red (R), and crimson (C). An automated, 96-well microplate fluorescent reader (bottom reading) was chosen for the assay because of the rapidity and high throughput that it offers. Tissue samples were digested by 4 M ethanolic KOH. The sedimentation method and dye extraction with Cellosolve acetate, as previously reported by others, were used for the sample processing. The bones were crushed and allowed to directly soak in Cellosolve acetate to extract the dye. The relationship between microsphere number and fluorescent intensity was linear over a broad range of microsphere numbers (80-20,000/mL). The coefficients of variation of within-run and between-run precision were 3.39 +/- 1.10% and 4.54 +/- 1.10%, respectively. Recovery of microspheres from tissues and blood averaged 94.3 +/- 2.5% and was not dependent on microsphere number. The spillover of the fluorescent signals into adjacent colors was 4.0 +/- 0.1% for O to Y, 8.1 +/- 0.4% for O to R, and 9.1 +/- 0.5% for R to C, and these values were constant over a wide range in concentrations of the microsphere pairs. No evidence was obtained for quenching of the emission of one fluorophore via photon absorption by another fluorophore. The measurements of regional blood flow obtained with fluorescent microspheres in three chronically instrumented fetal lambs at approximately 140 days gestation were similar to the flow estimates obtained using radioactive microspheres in four other fetal lambs at the same gestational age. The fluorescent method is thus a viable alternative to the radioactive technique for the measurement of regional blood flow to all fetal organs and tissues, particularly when an automated fluorescent microplate reader is employed to reduce analysis time.

Animals↗
PubMed1992

Regulation of estrus and ovulation in mares with progesterone or progesterone and estradiol biodegradable microspheres with or without PGF2alpha.

A single injection of a microsphere preparation, designed to deliver 1.25 gm progesterone and 100 mg estradiol-17beta at a controlled rate, for a duration of 12 to 14 days, produces accurate control of estrus and fertile ovulations in mares. Treatment is followed by PGF2alpha injection 14 days after steroid injection. The objectives of the present study were to determine whether estradiol added to the progesterone treatment or PGF2alpha administered at the end of the steroid treatment regimen, would improve synchronization of estrus and ovulation. A total of 45 cyclic horse mares was randomly assigned to 1 of 5 treatment groups as follows: Group 1 (control, n=9) sterile microsphere vehicle+sterile PGF2alpha vehicle 14 days after treatment with microsphere vehicle; Group 2 (n=9) progesterone and estradiol microspheres+PGF2alpha 14 days after treatment with microspheres; Group 3 (n=9) progesterone and estradiol microspheres+PGF2alpha vehicle 14 days after treatment with microspheres; Group 4 (n=9) progesterone + PGF2alpha 14 days after treatment with microspheres; and Group 5 (n=9) progesterone+PGF2alpha vehicle 14 days after treatment with microspheres. Addition of estradiol (P<0.05) or PGF2alpha (P<0.05) to the treatment regimen increased synchronization efficary by reducing variation in days to ovulation. All treatments significantly reduced variation in days to estrus compared with that of the controls; however, mares in the progesterone groups had an increased incidence of silent or shortened estrous behavior ( 2 days in duration compared with mares treated with progesterone (78 vs 33%, respectively). Therefore, estradiol and PGF2alpha each appear to reduce variation in days to ovulation while estradiol seems to promote better expression of posttreatment estrous behavior.

Journal Article↗
PubMed2004

A novel formulation design about water-insoluble oily drug: preparation of zedoary turmeric oil microspheres with self-emulsifying ability and evaluation in rabbits.

To enhance in vivo absorption of zedoary turmeric oil (ZTO) and develop new formulations of a water-insoluble oily drug, novel ZTO microspheres with self-emulsifying ability, called self-emulsifying microspheres here, were prepared in a liquid system by the quasi-emulsion solvent diffusion method. The microspheres containing hydroxypropyl methylcellulose acetate succinate (HPMCAS-LG), Talc and Aerosil 200 formed the stable surfactant-free emulsion when exposed to the pH 6.8 phosphate buffer, and were significantly different from the conventional self-emulsifying systems (SES), defined as isotropic mixtures of oil, surfactant and drug. Micromeritic properties, the efficiency of emulsification and the drug-release rate of the resultant microspheres were investigated. The bioavailability of the microspheres to the conventional self-emulsifying formulation for oral administration was evaluated in 12 healthy rabbits. A HPLC method was employed to determine the plasma concentration of Germacrone, an indexical component found in ZTO. The release rates of ZTO and Germacrone from the microspheres were enhanced significantly with increasing amounts of dispersing agents, and the efficiency of self-emulsification greatly depended on the HPMCAS-LG/Aerosil 200 ratio. The emulsion droplets released from the microspheres were much smaller than that of the conventional SES. The microsphere bioavailability (F) to the conventional SES for oral administration was 157.7%. Our method greatly improved the bioavailability of the water-insoluble oily drug from the self-emulsifying microspheres over the conventional SES and it is useful for the oily drug to form solid preparations.

Animals↗
PubMed2001

Effect of protein molecular weight on release from micron-sized PLGA microspheres.

This study investigates the effect of protein molecular weight on release kinetics from polymeric microspheres (1-3 microm). Proteins were encapsulated at high and low loadings in poly(lactic-co-glycolic acid) (PLGA) by a phase inversion technique. Mechanism of release from this type of microsphere appeared to be dependent on protein molecular weight for microspheres with low loadings (0.5-1.6%), while independent of protein molecular weight for microspheres with high loadings (4.8-6.9%). At low loadings, release of larger proteins was dependent on diffusion through pores for the duration of the study, while smaller proteins seemed to depend on diffusion through pores initially and on degradation at later times. Following an initial diffusion phase from low loaded microspheres, lysozyme and carbonic anhydrase, the two smallest proteins, exhibited lag phases with curtailed protein release followed by a phase of increased protein release between 4 and 8 weeks, a phenomenon not evident for larger proteins. It appears that by 8 weeks, PLGA had degraded enough to allow additional release of smaller proteins which were entrapped efficiently within the microspheres. Higher loaded microspheres, which have more interconnecting channels, did not exhibit the pronounced shift from diffusion-based to polymer degradation-based release seen with the lower loaded microspheres. Interestingly, microspheres encapsulating large proteins maintained sustained release rates for 56 days.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Egg albumin microspheres containing paracetamol for oral administration. I. In vitro characterization.

Different egg albumin microsphere systems for oral administration of paracetamol were prepared by the emulsion and capillary extrusion methods. The size of the microspheres depended on the method used to produce the microcapsules and also the size of the crystals of paracetamol. The effect of the following factors on in vitro dissolution were studied: different denaturation processes, variation in the ratio of paracetamol to albumin, size of microspheres, remnant oil in the microspheres, and the coating of the microspheres with membranes of polymethacrylates (Eudragit). The most important factors to control the release of paracetamol from the microspheres were the denaturation process and the use of waxes and membranes to delay the release of paracetamol from the microspheres. The egg albumin microspheres were very porous and permeable to water and thus the release of the paracetamol from the matrix was usually fast unless the microspheres were suitably coated, with, for example, Eudragit RL or RS.

Acetaminophen↗
PubMedDate not supplied

Stereospecific formulation and characterization of sustained release ibuprofen microspheres.

Ibuprofen microspheres were prepared from the racemate, (+)-S and (-)-R enantiomers using waxes such as ceresine and glyceryl stearate and stereospecifically characterized. The method of preparation of the microspheres was a hydrophobic congealable disperse phase encapsulation process and variables such as particle size, wax type, enantiomeric form were evaluated. Dissolution studies were carried out by a modified USP type II method and the samples were analysed by a stereospecific HPLC assay using S-(-)-1(1) naphthylethylamine as the derivatizing agent and fenoprofen as the internal standard. The mean particle sizes of (+)-S and (-)-R enantiomers determined by microscopy/image analysis were 64 and 99 microns respectively while that of the racemate was 48 microns. Differential Scanning Calorimetry (DSC) of ibuprofen and the enantiomers showed endothermic peaks at 72 and 55 degrees C respectively. Thermograms of the physical mixture and microspheres did not show the characteristic ibuprofen peak, indicating a change in crystallinity of the drug. Powder X-ray diffraction patterns of the enantiomers and racemic ibuprofen were found to be dissimilar indicating different crystal properties. The X-ray patterns for the microspheres did not show the characteristic peaks for the drug indicating that ibuprofen may be in solid solution with the waxes. Scanning electron micrographs of the microspheres showed a generally smooth and spongy appearance for the microspheres made of compritol and glyceryl stearate. Microspheres made from the paraffin waxes had rough and hard surface characteristics consistent with the higher melting point of the waxes. Ceresine microspheres made with the enantiomers had a rougher and more porous surface compared to the microspheres made with racemic ibuprofen. Stereospecific release of the recemate from the formulations was found to be sustained (T25 of 4 h), while release from the enantiomers was less sustained (T50 of 2 h). From the S:R ratios and statistical analysis of the data, the release of the enantiomers of ibuprofen from the formulations containing the racemate was found to be non-stereoselective.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Evaluation of 90:10 poly(D,L-lactide-co-glycolide) microspheres containing norethisterone: drug release and biodegradation.

Poly(D,L-lactide-co-glycolide) (PLG, 90:10) microspheres containing 20% norethisterone (NET) were prepared by solvent evaporation method. Microspheres in the size ranges of 65 to 100 microns were sterilized by irradiation and used for further study. In vitro release showed fairly constant release of NET from the above microspheres over more than 90 days. However, in vivo drug release determined by residual NET analysis after i.m. injection in rats indicated a faster release rate. About 95% of NET was released in a period of 45 days. At the dose of 80 mg of microspheres, vaginal estrus cycles were inhibited for 45 days compared to 27 days for the same dose of NET crystals in rats. Biodegradation of the microspheres was tested by direct measurement of molecular weight losses and SEM observation of morphological changes of the microspheres, which showed continuous erosion in the internal matrix of microspheres with the decrease of molecular weight of PLG until total collapse of microspheres, and biodegradation was faster in rats than in human serum at 37 degrees C in vitro. Total degradation of 90:10 PLG microspheres was less than 7 months in rats and more than 9 months in vitro.

Animals↗
PubMed2001

Studies on in vitro evaluation for the biocompatibility of various biomaterials: inhibitory activity of various kinds of polymer microspheres on metabolic cooperation.

Gap junctional intercellular communication is a function that plays an important role in maintaining cell and tissue homeostasis and in regulating cell growth, development, and differentiation. Change in this function when contacting fibroblasts with various polymer microspheres was estimated using the metabolic cooperation assay system. When the cells were in contact with the microspheres after their adhesion onto a substrate, the function did not alter. However, when they were in contact with precoated microspheres on test dishes, the function was inhibited as the quantity of microspheres increased. Moreover, the inhibition level increased as the diameters of polyethylene and polystyrene microspheres decreased. However, no inhibition was observed if precoated microspheres were composed from poly(L-lactic acid). These findings suggest that the size and the material of microspheres, and how cells recognize the microspheres, are factors affecting cell function of gap junctional intercellular communication. Therefore, estimating this function may provide valuable information about the biocompatibility of many kinds of materials even in the form of particles.

Animals↗
PubMed2003

Quantitative image analysis of cellular protein translocation induced by magnetic microspheres: application to the EGF receptor.

BACKGROUND: The molecular analysis of intracellular signal transduction requires technologies that address quantitatively the activation of signaling proteins and formation of molecular complexes without disrupting cellular integrity. METHODS: Cells expressing the epidermal growth factor receptor (EGFR) in its endogenous form or fused to green fluorescent protein were incubated with 1-microm microspheres covalently functionalized with EGF. The disposition of the plasma membrane about the microspheres was analyzed by high-resolution confocal microscopy in combination with computational resolution enhancement and optimized fixation procedures. Receptor activation and translocation of signaling proteins to the microspheres was quantitated by image processing protocols for recovering the microsphere-associated fluorescence and the fluorescence in the local environment. RESULTS: EGF-functionalized microspheres were internalized in an activation-dependent manner similar to that of the soluble growth factor. The correlation of receptor activation and recruitment of a signaling protein was analyzed quantitatively by isolating immunofluorescence signals from the microspheres and from their immediate environment. CONCLUSIONS: The microsphere-based approach provides a quantitative analysis of cellular signal transduction with subcellular resolution under conditions maintaining cellular integrity. The analysis of signaling-induced (co)localization of proteins around a microsphere complements other technologies directly probing for molecular interactions such as fluorescence resonance energy transfer.

Animals↗
PubMed2005

Signal transduction of erbB receptors in trastuzumab (Herceptin) sensitive and resistant cell lines: local stimulation using magnetic microspheres as assessed by quantitative digital microscopy.

BACKGROUND: ErbB2 (HER-2), a member of the epidermal growth factor (EGF) receptor family, is a class I transmembrane receptor tyrosine kinase. Although erbB2 has no known physiologic ligand, it can form complexes with other members of the family and undergo transactivation of its very potent kinase activity, thereby initiating downstream signaling and cell proliferation. ErbB2 is a frequent pathologic marker in ductal invasive breast carcinomas and is targeted by using a specific humanized monoclonal antibody, trastuzumab (Herceptin). The antibody is effective in only 20% to 50% of erbB2-positive tumors, and this resistance, as yet poorly understood, constitutes a major therapeutic challenge. METHODS: Magnetic microspheres coated with ligands or antibodies are widely used for separation of proteins and cells and allow localized, high intensity, and precisely timed stimulation of cells. We used EGF- and trastuzumab-covered paramagnetic microspheres, quantitative confocal laser scanning microscopy, and digital image processing to investigate the (trans)activation of and local signal propagation from erbB1 and erbB2 on trastuzumab sensitive and resistant carcinoma cell lines expressing these receptors at high levels. RESULTS: On A431 cells expressing high levels of endogenous erbB1 and transfected erbB2-mYFP (A4-erbB2-mYFP F4 cell line), EGF-coupled-microspheres activated erbB1 and transactivated erbB2-mYFP. In two other cell lines with comparable erbB2 expression but lower levels of erbB1, EGF microspheres transactivated erbB2 less efficiently. Trastuzumab in solution activated erbB2 on A4-erbB2-mYFP and the trastuzumab sensitive SKBR-3 cells, but only negligibly on the resistant JIMT-1 cells that showed a 10 times higher K(d) for the antibody. Nevertheless, pronounced erbB2 activation and tyrosine phosphorylation could be detected after stimulation with trastuzumab-coupled microspheres in all cell lines, although transactivation of erbB1 was negligible. Receptor phosphorylation was restricted to the immediate proximity of the microspheres, i.e., receptor clusters external to these locations remained inactive. CONCLUSION: ErbB1 ligand and erbB2 specific antibody attached to magnetic microspheres are efficient tools in assessing erbB activation, localized signal propagation, and erbB heterodimer formation. Trastuzumab coupled to microspheres is more efficient at accessing erbB2 and activating it than trastuzumab in solution.

Animals↗
PubMed2005

Development of new injectable bulking agents: biocompatibility of radiopaque polymeric microspheres studied in a mouse model.

Radiopaque polymeric microspheres have a potential as new bulking agents for treatment of stress urinary incontinence (SUI). The advantage over existing bulking agents lies in their X-ray visibility in situ; other polymeric bulking agents (e.g., PTFE or silicone rubbers) are practically radiolucent (i.e., incapable of absorbing X-radiation). Radiopacity is useful in practice because of the high spatial accuracy of X-ray imaging. For instance, X-ray fluoroscopy can be used to assess possible migration of the bulking agent over time or to provide guidance in cases in which a second injection of a bulking agent is necessary (repeated treatment of SUI). Biocompatibility of injected radiopaque microspheres was investigated in vivo by using the mouse as a model. Microspheres were injected subcutaneously (9 animals) or intramuscularly (9 animals), and follow-up was 8 days or 3 months. X-ray fluoroscopy gave clear images of the microspheres as an ensemble, and it was found that no migration occurred during 3 months. Histopathology confirmed that all microspheres stayed close to the site of the injection. The microspheres appeared to be well tolerated; only a few giant cells, manifesting a mild inflammatory reaction, were encountered. At 3 months, capillary blood vessels were observed throughout the microsphere beds, and macrophages and fibroblast cells were seen in between the microspheres. This is encouraging with respect to the intended application, although it must be acknowledged that the data refer merely to a mouse model. Further experiments with larger, more representative models (rabbit and goat) are in progress.

Animals↗
PubMed2006

Controlled release of bioactive doxorubicin from microspheres embedded within gelatin scaffolds.

We have encapsulated the chemotherapeutic agent doxorubicin into biodegradable polymer microspheres, and incorporated these microspheres into gelatin scaffolds, resulting in a controlled delivery system. Doxorubicin was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) using a double emulsion/solvent extraction method. Characterization of the microspheres including diameter, surface morphology, and in vitro drug release was determined. The release of doxorubicin up to 30 days in phosphate buffered solution was assessed by measuring the absorbance of the releasate solution. Gelatin scaffolds were crosslinked using glutaraldehyde and microspheres were added to gelatin during gelation. The murine mammary mouse tumor cell line, 4T1, was treated with various doses of doxorubicin. A propidium iodide assay was utilized to visualize dead cells. Using a Transwell basket assay, PLGA microspheres and gelatin constructs were suspended above 4T1 cells for 48 h. Viable cells were determined using the CyQUANT cell proliferation assay. Results indicate that the release was controlled by the incorporation of PLGA microspheres into gelatin constructs. A significant difference was seen in the cumulative release over days 5-16 (p < 0.05). The bioactivity of doxorubicin released from the microspheres and scaffolds was maintained as proven by significant reduction in viable cells after treatment with PLGA microspheres as well as with the gelatin constructs (p < 0.001). The drug-polymer conjugate can be used as a controlled drug delivery system in a biocompatible scaffold that could potentially promote preservation of soft tissue contour.

Adsorption↗
PubMed2006

Biodegradable polymer-silica xerogel composite microspheres for controlled release of gentamicin.

Single and double layered composite microspheres were prepared by encapsulating gentamicin-loaded silica xerogels with biodegradable PLGA polymers (poly(DL-lactide-co-glycolide)). The in vitro drug release properties of both the composite microspheres were investigated. The single layered composite microspheres showed a high initial burst, followed by two sustained release stages lasting for approximately 6 weeks. The two sustained release stages of the single layered composite microspheres could be attributed to the swelling and bulk erosion of the polymer encapsulations, respectively. In comparison with the single layered composite microspheres, the double layered composite microspheres realized a much reduced initial burst together with three sustained release stages. The whole release period of the double layered composite microspheres could last more than 9 weeks. These distinct behaviors make the double layered composite microspheres promising as a new drug release material for localized drug delivery applications.

Biocompatible Materials↗
PubMed2007

Growing tissue-like constructs with Hep3B/HepG2 liver cells on PHBV microspheres of different sizes.

In this study, an oil-in-water emulsion solvent evaporation technique was used to fabricate poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV, 8% PHV), microspheres as scaffold, to guide liver cell growth. Human hepatoma cell lines, HepG2 and Hep3B, were cultured in vitro on both the microspheres and polymer films. SEM and optical microscope images showed that multilayer cells were formed among the microspheres to bridge them together and developed into cell-construct aggregates after 1 week of culture. MTT results showed that the cell proliferation on the microspheres was more than two times higher than that on the films after 12 days of culture. The cells seeded on microspheres secreted albumin 2-4 times more than that on the positive control after 1 week of culture, which indicated that this hepatic function was greatly improved by the aggregation of cells on microspheres. Although HepG2 failed to express P-450 activity, this hepatic function was preserved when Hep3B cultured on microspheres. All the results indicated that PHBV microspheres are appropriate scaffolds for liver tissue engineering.

Cell Culture Techniques↗
PubMed1981

Acute hemodynamic effects and blood pool kinetics of polystyrene microspheres following intravenous administration.

The acute hemodynamic effect of intravenous administration of polystyrene microspheres was investigated and correlated with their distribution pattern and kinetics. Microspheres of three diameters (3.4, 7.4, and 11.6 micrometer) were administered. The 7.4- and 11.6-micrometer diameter microspheres were filtered by the pulmonary capillary network following intravenous administration, the majority during the first pass. There was no significant hemodynamic effect following administrations of the 7.4- and 11.6-micrometer diameter microspheres in doses as high as 3.0 X 10(9) and 6.1 X 10(8) respectively (total cross-sectional area of 1.3 X 10(11) and 6.4 X 10(10) micrometer2, respectively). Intravenous administration of 3.4-micrometer diameter microspheres produced significant dose-dependent systemic hypotension and depression of myocardial performance at dosages as slow as 1.0 X 10(10) (cross-sectional area of 9.1 X 10(10) micrometer2). These differences in acute hemodynamic effect from the 7.4- and 11.6-micrometer diameter microspheres may be due to the differences in distribution kinetics and fate of the 3.4-micrometer diameter microspheres, which readily pass through the lungs to the spleen. Although elimination of the smaller spheres from the blood during the first 6-8 min was rapid, i.e., t 1/2 = 1.62 and 1.72 min from the venous and arterial blood circulation, respectively, levels of 10(3) spheres/g of blood were present in the circulation for greater than 1 hr. These findings must be considered in the planning of intravenous administration of microspheres as a drug delivery system to target organs.

Animals↗
PubMed1984

Characterization of drug-loaded poly(d,l-lactide) microspheres.

Lomustine and progesterone have been incorporated in biodegradable poly(d,l-lactide) microspheres by evaporating dichloromethane from stirred dichloromethane-in-water emulsions. Spherical microspheres with lomustine or progesterone payloads less than or equal to 23% were obtained. Higher lomustine payloads gave irregularly shaped particles. Microspheres with less than or equal to 68% progesterone were obtained, but free drug crystals formed on the surface of such microspheres. Increased agitation rates decreased mean microsphere size. Addition of drug to the dichloromethane phase increased average particle size relative to that obtained with drug-free microspheres prepared under the same experimental conditions. Complete evaporation of the dichloromethane, while the medium was continuously stirred, promoted formation of free drug crystals in the aqueous phase. Increased emulsifier concentrations did not significantly enhance drug incorporation efficiency within the microspheres. Shelf-life stability of lomustine and progesterone was reduced by incorporation in the microspheres, presumably due to their molecular dispersion in the poly(d,l-lactide).

Crystallization↗
PubMed1986

5-Fluorouracil:carnauba wax microspheres for chemoembolization: an in vitro evaluation.

5-Fluorouracil:carnauba wax microspheres were prepared using a meltable dispersion process with the aid of a surfactant as a wetting agent. It was noted that only hydrophilic surfactants were able to wet the 5-fluorouracil and substantially increased its content in the microspheres. No marked effect was observed in the particle size distribution of the solid microspheres as a function of the nature of the surfactant. Increasing the stirring rate in the preparation process decreased, first, the mean droplet size of the emulsified melted dispersion in the vehicle during the heating process, and, consequently, the mean particle size of the solidified microspheres during the cooling process. 5-Fluorouracil cumulative release from the microspheres followed first-order kinetics, as shown by nonlinear regression analysis. Although the kinetic results were not indicative of the true release mechanism from a single microsphere, it was believed that 5-fluorouracil release from the microspheres was probably governed by a dissolution process, rather than by a leaching process through the carnauba wax microspheres.

Fluorouracil↗
PubMed2004

Preparation and characterization of biodegradable microspheres containing hepatitis B surface antigen.

Poly-DL-lactide-poly(ethylene glycol) (PELA) microspheres containing Hepatitis B surface antigen (HBsAg) were elaborated by a solvent extraction method based on the formation of a double water/oil/water (w/o/w) emulsion. Microspheres were characterized in terms of morphology, size and size distribution, encapsulation efficiency, and the efficiency of microsphere formation (EMF). Transmission electron microscopy (TEM) and polyacrylamide gel electrophoresis (PAGE) were used to investigate the structural integrality of HBsAg encapsulated in PELA microspheres. The release profile was investigated by the measurement of antigen present in the release medium at various intervals. The PELA-10 microspheres displayed the highest antigen encapsulation efficiency (about 80%), and antigen molecules could be stabilized in the PELA-10 microspheres during the preparation process. It suggested that the PELA microspheres had a great potential as a new polymer adjuvant for HBsAg. The release of Hepatitis B surface antigen from poly-DL-lactide-poly(ethylene glycol) microspheres.

Adjuvants, Immunologic↗