Degradation of double-walled polymer microspheres of PLLA and P(CPP:SA)20:80. II. In vivo degradation

Double-walled (DW) polymer microspheres with a core of poly(1,3-bis-(p-carboxyphenoxy propane)-co-(sebacic anhydride)20:80 (P(CPP:SA)20:80) and an external coat of poly(L-lactic acid) (PLLA) were implanted subcutaneously and intramuscularly and were allowed to degrade for up to 6 months. The tissue surrounding the implant was fixed and sectioned for histological evaluation by light and scanning electron microscopy. The remaining polymer was extracted with chloroform and analyzed by gel permeation chromatography (G PC), Fourier-transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC). The inner core of the more hydrolytically labile P(CPP:SA)20:80 degraded first, becoming more granular over time. The PLLA coating showed no changes morphologically. The DW microspheres induced a stronger inflammatory response during the first week than did the SW PLLA microspheres, but this resolved by the second week. The SW PLLA microspheres showed no changes by SEM or optical microscopy. No differences in degradation were seen between samples implanted subcutaneously and those implanted intramuscularly. In vivo degradation was correlated to the results of an in vitro degradation study published as the first paper in this two paper series.     

Retinoic acid regulates selectively the expression of immediate early response genes in PC12 cells

Six modular acetabular components were evaluated to determine whether screw holes in the metal shell offer a route for fluid and debris into the acetabular bone stock. A 56-mm acetabular shell for each trial was mounted to a sealed chamber and loaded at a 25 degrees angle under axial loads of 270-2,700 N and +/- 2.5-N-m torsional load. Polystyrene microspheres (average diameter, 0.5 microm) were placed in double-deionized water at 300 mmH2O pressure in a sealed chamber above the component. The only channel between the fluid above and the collecting chamber below was through the cup-liner interface and 1 screw hole. Fluid and debris in the collecting chamber were harvested after 1,000,000 cycles. The collected sample was filtered through a 0.2-microm-pore filter and analyzed under electron microscopy for evidence of microspheres. Water and polystyrene microspheres were isolated in the collecting chamber for all trials except the Reflection cup (Smith & Nephew Orthopaedics, Memphis, TN) with a screw hole cover and the Micro-Seal cup (Whiteside Biomechanics, St. Louis, MO) with a peripheral seal. A screw placed in the screw hole of the Reflection cup failed to seal the interface. The peripheral seal around the rim of the Micro-Seal polyethylene prevented fluid and particle flow between the metal shell and polyethylene liner.     

Preparation and characterization of pH-sensitive proteinoid microspheres for the oral delivery of methotrexate

Prot A7, a polypeptidic proteinoid composed of seven different amino acids, was synthesized and microspheres of 1-5 microm size were prepared by the self-assembly process. The morphological characterization of the microspheres was carried out using optical microscopy and SEM (scanning electron microscopy). Emphasis also has been made on studying the mechanism behind the microsphere formation and to relate it with the conformation of the polypeptide. These self-assembled microspheres were found to be pH-sensitive in aqueous medium. The suitability of the Prot A7 microspheres as a carrier for gastric irritant drugs was verified by choosing methotrexate (MTX) as a model drug. MTX was entrapped in proteinoid microspheres and its utility for the oral delivery system was verified by carrying out the drug dissolution studies in simulated gastric medium (pH 1.2) and neutral medium of the blood (pH 7) under physiological conditions. The pH responsive dissolution behaviour of the microspheres was clarified.     

Precipitation of VC in ferrite and pearlite during direct transformation of a medium carbon microalloyed steel

Transmission electron microscopy of an air-cooled medium carbon (0.5 wt pct) steel containing 0.1 wt pct vanadium has shown that VC precipitates by the interphase mecha-nism during transformation to both proeutectoid and pearlitic ferrite. Depending upon the rate of transformation, a considerable proportion of the available vanadium may remain in supersaturated solid solution and can be precipitated as VC upon subsequent aging at 700°C. It was found that the proportion of proeutectoid ferrite, the interlamellae pearlite spac-ings and the VC precipitate dispersion parameters all decreased with increasing cooling rate in as-transformed material. G. FRIMODIG were formerly undergraduate students     

Molecular genetic analysis of giant cell glioblastomas

Encapsulation of vaccines in biodegradable microspheres provides excellent mucosal immunogens with a high potential for immunization against bacterial infections. We tested the protective immunity elicited by intragastric vaccination with phosphorylcholine (PC) encapsulated in poly(DL-lactide-co-glycolide) (DL-PLG) microspheres against Salmonella typhimurium in a mouse model of invasive intestinal infection. We chose PC as the antigen because it was found to elicit an immune response after intestinal exposure of mice to PC-bearing S. typhimurium and because anti-PC immunity protects mice against Streptococcus pneumoniae, another PC-bearing microorganism. Mice were primed intragastrically on days 1, 2, and 3 and boosted on days 28, 29, and 30 with PC (280 microg) coupled to porcine thyroglobulin (PC-thyr) encapsulated in DL-PLG microspheres, free PC-thyr, or blank microspheres. A significant rise in anti-PC immunoglobulin A (IgA) titers, as measured by an enzyme-linked immunosorbent assay, was observed in the intestinal secretions after immunization with PC-loaded microspheres, compared to the titers of mice immunized with free PC-thyr or blank microspheres. This antibody response peaked 14 days after the last boost and correlated with a highly significant resistance to oral challenge by S. typhimurium C5 (P < 10(-3)). Control mice were primed intraperitoneally on day 1 with 15 microg of PC in complete Freund's adjuvant and boosted on days 10, 14, and 20 with the same dose without adjuvant but via the same route. In these mice, the levels of anti-PC IgA in intestinal secretions were equivalent to those of the mice intragastrically immunized with PC-loaded microspheres, but protection was significantly weaker, suggesting that either the IgAs were not functional or that other immune mechanisms are important in protection. Taken together, our results highlight the potential of antigen encapsulation in DL-PLG microspheres for eliciting protective immunity against invasive intestinal bacterial diseases and suggest that a similar strategy could be used against diseases caused by other PC-bearing microorganisms.     

Serological response to in vitro-shed antigen(s) of Tritrichomonas foetus in cattle

We developed a serological assay for detection of (l) an erythrocyte-adhering molecule(s) shed by the bovine venereal pathogen Tritrichomonas foetus and (II) serum antibodies to this antigen(s) in exposed cattle. Sera from exposed and unexposed cattle were tested for their ability to induce complement-mediated lysis of bovine erythrocytes that had been previously incubated overnight at room temperature in pH-adjusted supernatants of T. foetus culture media. Eight of 180 serum specimens from six groups of presumably unexposed cows or heifers showed a positive (> or = 1:2) hemolytic titer (specificity = 95.6%). Thirteen of 14 females in two experimentally infected groups showed a positive hemolytic titer following infection (sensitivity = 94%). In experimentally infected heifers, there was little correlation (r2 = 0.33) between serum hemolytic titers with respect to shed antigen and titers obtained in serum enzyme-linked immunosorbent assays in which whole T. foetus served as the antigen. Serum hemolytic titers rose 3 to 4 weeks sooner than did previously described vaginal mucus immunoglobulin G1 or immunoglobulin A titers with respect to whole-cell antigen or TF1.17 subunit antigen, respectively. Among 14 chronically infected bulls, only 6 (43%) showed a positive hemolytic titer. This study is the first, to our knowledge, to show a specific serological response in the host to an in vitro-shed antigen(s) of T. foetus and suggests a useful diagnostic test for potentially exposed herds.     

Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis

The aim of this study was to determine whether latent viral infection is associated with idiopathic pulmonary fibrosis (IPF), an interstitial lung disease whose aetiology remains to be elucidated. Cytomegalovirus (CMV) immunoglobulin G (IgG) and complement fixation (CF), Epstein-Barr (EB) viral capsid antigen (VCA) IgG, herpes simplex virus (HSV) IgG, adenovirus CF, and parainfluenza 3 virus haemagglutinin inhibition (HI) titres were measured in the serum from patients with pulmonary diseases. The study included five subject groups: 35 normal controls (aged (mean +/- SD) 38 +/- 17 yrs); 43 IPF (63 +/- 10 yrs), seven collagen vascular disease-related interstitial pneumonitis (CVD-IP) (62 +/- 12 yrs); 22 sarcoidosis (36 +/- 14 yrs); and 17 emphysema (66 +/- 11 yrs). Levels of CMV IgG in IPF (87.6 +/- 51.7) and CVD-IP (101.2 +/- 69.9) were significantly elevated compared to those in the control (30.9 +/- 24.1), sarcoidosis (34.4 +/- 38.3) and emphysema groups (40.3 +/- 24.6), whereas CMV immunoglobulin M (IgM) was generally below the limit of detection. Similarly, CMV CF titres in IPF and CVD-IP were elevated compared to those in other diseases. EB VCA IgG titres in IPF, CVD-IP and emphysema and HSV IgG in IPF were also elevated. In contrast, adenovirus CF and parainfluenza 3 HI titres demonstrated no significant difference among all of the groups investigated. Increases in cytomegalovirus immunoglobulin G and complement fixation titres with negative cytomegalovirus immunoglobulin M suggest that latent cytomegalovirus infection may be more prominent in idiopathic pulmonary fibrosis or collagen vascular disease-related interstitial pneumonitis. Together with the elevation of Epstein-Barr virus viral capsid antigen and herpes simplex virus immunoglobulin G in idiopathic pulmonary fibrosis and/or collagen vascular disease-related interstitial pneumonitis, it is rational to assume that these viruses may be implicated in the development of pulmonary fibrosis. Further study is necessary to investigate the relationship between latent viral infection and pulmonary fibrosis.     

Impact of high-dose oral acyclovir prophylaxis on cytomegalovirus (CMV) disease in CMV high-risk renal transplant recipients

Recent studies showed contradictory results concerning the efficacy of oral acyclovir in the prevention or amelioration of cytomegalovirus (CMV) disease after renal transplantation (TX). This study evaluated the incidence and severity of CMV disease within the first year after TX in high-risk renal transplant recipients (CMV-seropositive donor, seronegative recipient) treated prophylactically with oral acyclovir (800 to 3200 mg/day) over a period of 12 wk (ACY, N = 22), compared with high-risk patients randomly assigned as controls (CO, N = 10). Follow-up for CMV infection included serological determination of CMV-specific immunoglobulin G and immunoglobulin M antibodies, antigen detection in peripheral blood leukocytes (PP 65), shell vial culture (blood), and virus isolation/early antigen detection (urine). Severity of CMV disease was quantified by a scoring system for CMV-related symptoms. Nine patients (40.1%) in the acyclovir group and four patients (40%) in the control group developed CMV disease. Neither severity (ACY, 11.4 versus CO; 12.5 points score), nor duration of disease (ACY, 21 days; CO, 22 days), nor transplant function at the end of the observation period differed significantly. The onst of CMV disease was not delayed significantly in acyclovir-treated patients compared with controls (ACY, 47 +/- 34 days versus CO, 27 +/- 14 days after TX, not significant). Our results show no beneficial effect of oral acyclovir prophylaxis in CMV high-risk renal transplant recipients.     

High density lipoprotein conversion mediated by human plasma phospholipid transfer protein

Phospholipid transfer protein (PLTP) was purified from lipoprotein-free human plasma, obtained upon treatment of plasma with dextran sulfate and Ca2+, by employing a series of column chromatography. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified PLTP showed a single main band, corresponding to the molecular mass of 78 kDa. However, isoelectric focusing of the purified preparation gave multiple bands with pI ranging from 4.3 to 5.1, indicative of microheterogeneity. Purified PLTP was shown to possess not only phospholipid transfer activity, but also high density lipoprotein (HDL) conversion activity (Tu, A.-Y., Nishida, H. I., and Nishida, T. (1990), FASEB J. 4, A2148; Jauhiainen, M., Metso, J., Pahlman, R., Blomqvist, S., van Tol, A., and Ehnholm, C. (1993) J. Biol. Chem. 268, 4032-4036). Isolated HDL3 was enlarged to the size of HDL2b upon incubation with purified PLTP for 6 h at 37 degrees C at the PLTP/HDL3 molar ratio of approximately 1:45. Both the HDL conversion and the phosphatidylcholine transfer activities of purified PLTP were effectively inhibited by rabbit anti-PLTP immunoglobulin G. The primary importance of PLTP in the HDL enlargement that occurs in human plasma upon incubation at 37 degrees C was shown by the strong inhibitory effect of the anti-PLTP immunoglobulin G. The process of PLTP-mediated HDL enlargement was accompanied by the release of apoproteins, primarily apoA-I. HDL3 enlargement mediated by PLTP was effectively inhibited by the addition of free fatty acids.     

DNA and a CpG oligonucleotide derived from Babesia bovis are mitogenic for bovine B cells

DNAs from bacteria and variety of nonvertebrate organisms, including nematodes, mollusks, yeasts, and insects, cause polyclonal activation of murine B lymphocytes. Similar studies have not been reported for bovine B cells, and to date no studies have reported mitogenic properties of protozoal DNA for any species. However, we and others have observed that protozoal parasite antigens can induce the proliferation of lymphocytes from nonexposed donors. Extending these studies, we now show that the mitogenic property of protozoal antigen preparations is in part attributable to parasite DNA and that Babesia bovis DNA is directly mitogenic for bovine B cells. DNase treatment of B. bovis extracts abrogated B. bovis-induced proliferation of peripheral blood mononuclear cells from nonexposed cattle. Like DNAs from other organisms that were mitogenic for murine B cells, B. bovis DNA is largely nonmethylated and induced a dose-dependent proliferation of bovine B cells, which was reduced upon methylation. Furthermore, B. bovis and E. coli DNAs enhanced immunoglobulin secretion by cultured B cells, inducing moderate increases in immunoglobulin G1 and stronger increases in immunoglobulin G2. Because certain nonmethylated CpG motifs present in bacterial DNA are known to stimulate proliferation of murine and human B cells, an 11-kb fragment of B. bovis DNA was analyzed for CG dinucleotide content and for the presence of known immunostimulatory sequences (ISS) centered on a CG motif. The frequency of CG dinucleotides was approximately one-half of the expected frequency, and several CpG hexameric sequences with known activity for murine B cells were identified. An oligodeoxynucleotide containing one of these ISS (AACGTT), which is present within the rhoptry-associated protein-1 (rap-1) open reading frame, was shown to stimulate B-cell proliferation. These ISS may be involved in host immune modulation during protozoal infection and may be useful as vaccine adjuvants.     

巨磁阻生物传感器对磁性聚苯乙烯微球检测

采用改进的悬浮聚合法制备磁性聚苯乙烯微球.利用扫描电子显微镜和振动样品磁强计对所合成磁性微球的尺寸和磁性能进行分析表征.采用巨磁阻生物传感器检测磁性微球的数量.结果表明:磁性微球粒径大小为0.5~50μm,比饱和磁化强度为4.56 A·m²·kg^-1.巨磁阻生物传感器对磁性聚苯乙烯微球数量具有很好的可检测性.在一定的范围内,随着磁性微球数量的增多,传感器的输出信号增强.在磁性微球一定数量的情况下,随着磁性微球粒径的增大,传感器的电阻变化量先增大后减小.     

Luminescent-plasmonic core–shell microspheres,doped with Nd3+ and modified with gold nanoparticles,exhibiting whispering gallery modes and SERS activity

Multifunctional core/shell type,luminescent-plasmonic material composed of lanthanide doped microspheres(≈50 μm) and gold nanoparticles(Au NPs;≈10-20 nm) deposited onto their surface,were successfully prepared(Nd~(3+):YAS@Au).The material was synthesized to combine the luminescence properties of the Nd~(3+)-doped microspheres,i.e.whispering resonance with plasmonic activity of the surface Au NPs,i.e.surface enhanced Raman scattering(SERS) effect,within a single,micro-sized material.The luminescent-plasmonic microspheres were used as the active SERS substrate for detection of the organic probe,and for generation of Whispering Gallery Modes(WGM),which red-shift together with increasing laser power(temperature elevation).The products obtained were analysed with optical,scanning and transmission electron microscopy(SEM and TEM),as well as by Raman,absorption and photoluminescence spectroscopies.     

Controlled delivery of therapeutics from microporous membranes. I. Fabrication and characterization of microporous polyurethane membranes containing polymeric microspheres

This paper describes a process for the inclusion of polymer microspheres in microporous polyurethane tubes and membranes. These composites were fabricated via a spray, phase-inversion technique using Cardiothane 51, a medical grade polyurethane, and either spray-dried poly(D,L-lactide-co-glycolide 50:50) microspheres or commercially available fluorescent polystyrene-latex microspheres. Characterization of the polyurethane membranes was performed using Fouriertransform infrared spectroscopy, differential scanning calorimetry, dynamic mechanical analysis, hydraulic permeability testing, scanning electron microscopy, and visible and fluorescence light microscopy. The results indicated the feasibility of layering microspheres throughout the microporous membrane or wall of the microporous tube, and the potential of such composite structures for local delivery of bioactive substances.     

Biogenic synthesis and catalysis of porous CeO2 hollow microspheres

Porous CeO2 hollow microspheres were successfully prepared through a facile process by using the rape pollen as the biotem-plate. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), the N2 adsorption and desorption, X-ray diffraction (XRD), UV-vis diffuse reflectance spectra, and hydrogen temperature-programmed reduction (H2-TPR) were used for their characterization. The results showed that the obtained materials exhibited the same morphology as that of the pollen template, with a diameter of ca. 10 μm, and the surface was evenly covered with a special network-like structure with mesh size of about 0.3 μm, and the Brunauer-Emmett-Teller (BET) surface area was measured to be 156 m2/g. The detailed property investigation inferred that the product exhibited better photocatalytic activity in acid fuchsine decolorization under daylight because of higher surface area, smaller crystallite size and higher oxygen capacity.     

Analysis of commercial mini-bus accidents

The major challenge in liquid sustained-release oral suspensions is to minimize drug diffusion into the suspending medium and to retain the original properties of the microparticles during storage. Diclofenac wax microspheres prepared by the hydrophobic congealable disperse phase method were formulated as a sustained release suspension and stored at three different temperatures (25, 37 and 45 degrees C) for 3 months, to evaluate the physical and chemical stability of the suspended microspheres. Suspensions of microspheres stored at ambient temperatures were both physically and chemically stable, but at higher temperatures, up to 45 degrees C, there was a decrease in drug release due to scaling and melting on the microsphere surface as observed by scanning electron microscopy. However, on prolonged storage, up to 90 days, especially at 45 degrees C, temperature became a dominant factor causing an increase in drug release. The suspension of diclofenac microspheres was chemically stable for 3 months, while the plain drug suspension exhibited slight degradation.     

高磁性微球的制备及在冶金废水处理中的应用

制备了一种高磁性氧化钛,氧化硅包覆四氧化三铁微球材料(Fe3O4@SiO2@TiO2),并通过透射电子显微镜和扫描电子显微镜对制备的材料进行表征。制备材料具有很好的分散性,可以很好地分散在水溶液中,通过外加磁场,分散的磁性材料可以很快和水体分离。氧化硅和氧化钛两层外壳很好地保护了铁核,因此制备的材料在酸性溶液中有很好的稳定性,可以用来固相萃取冶金废水中的金属离子。     

Microencapsulation of hepatitis B core antigen for vaccine preparation

PURPOSE: To prepare poly(lactide-co-glycolide)(PLGA) microspheres containing recombinant hepatitis B core antigen (HBcAg; Mw = 3,600,000) by a w/o/w emulsion/solvent evaporation method and evaluate the possibility of this system as a potent long-acting carrier for hepatitis B core antigen in mice. METHODS: Various additives had been incorporated in the internal aqueous phase during the process of microencapsulating HBcAg, HBcAg antigenicity in the medium extracted from the prepared microspheres were measured by ELISA. Shape confirmation of the HBcAg antigen was performed by a sucrose gradient velocity centrifugal technique. For in vivo study, prepared microspheres were administered subcutaneously to Balb/C mice, and the serum IgG level was determined by ELISA. RESULTS: The inactivation of HBcAg by methylene chloride was dramatically reduced by the addition of gelatin (4-8% (w/v)) to the internal aqueous phase during the preparation. Further improvement of the loading efficiency to almost 61% resulted with cooling (4 degrees C). The prepared microspheres (4.27 microm+/-1.23 microm) containing 0.15% HBcAg displayed burst release (50-60% within 2 days). In subcutaneous inoculation, the adjuvant effect of PLGA microspheres was almost the same as that of the complete Freund's adjuvant. Whereas oral inoculation using the microspheres was not effective. CONCLUSIONS: The pH of the added gelatin seemed to be the key to the stabilization of HBcAg from various stability tests and CD spectrum study. Finally, the possibility of using this system as a potent long-acting hepatitis B vaccine was demonstrated.     

Craniofacial and TMJ effects after glutamate and TRH microsphere implantation in proximity to trigeminal motoneurons of growing rats

The sequelae of sustained, in vivo delivery of two important neurotransmitter substances, glutamate and thyrotropin-releasing hormone (TRH), upon craniofacial growth and development have previously not been investigated. Our purpose was to document and compare the relative effects of glutamate and TRH microspheres stereotactically placed in proximity to trigeminal motoneurons within the trigeminal motor nucleus. The following null hypotheses were tested: (1) TRH microspheres in proximity to trigeminal motoneurons have no significant effect upon the craniofacial skeleton, and (2) there are no significant differences between the relative effects of chronic, long-term delivery of glutamate and TRH upon the neuromusculoskeletal system of growing rats. Forty male Sprague-Dawley rats were divided into 4 experimental groups (glutamate microspheres, TRH microspheres, blank microspheres, sham surgeries) and underwent stereotactic neurosurgery at 35 days; 5 rats of each group were killed at 14 and 21 days for data collection. Histology revealed that implants were clustered in the pontine reticular formation, close to the ventrolateral tegmental nucleus. Both glutamate and TRH rats had implant-side deviation of their facial skeleton and snout regions; 4 x 2 ANOVA and post hoc t-tests revealed significant (P < or = 0.05, 0.01) differences between groups and sides for motoneuron count, muscle weight, and osteometric data. TRH rats also demonstrated larger implant-side TMJ discs and mandibular fossae in comparison with the other groups. The stated null hypotheses were therefore rejected.     

Liposomes containing lipid A serve as an adjuvant for induction of antibody and cytotoxic T-cell responses against RTS,S malaria antigen

Encapsulation of soluble protein antigens in liposomes was previously shown to result in processing of antigen via the major histocompatibility complex class I pathway, as evidenced by costaining of the trans-Golgi region of murine bone marrow-derived macrophages (BMs) by fluorophore-labeled liposomal antigen and by a trans-Golgi-specific fluorescent lipid. Evidence is presented here that free or liposome-encapsulated RTS,S, a particulate malaria antigen consisting of hepatitis B particles coexpressed with epitopes from the Plasmodium falciparum circumsporozoite protein, also was localized in the trans-Golgi after incubation with BMs, suggesting processing by the class I pathway. An in vivo cytotoxic T-lymphocyte (CTL) response was detected, however, only after immunization with RTS,S encapsulated in liposomes containing lipid A and not after immunization with free RTS,S or with RTS,S encapsulated in liposomes lacking lipid A. Therefore, intracellular delivery of antigen containing CTL epitopes to the Golgi of BMs does not necessarily result in a CTL response in vivo unless an additional adjuvant, such as liposomes containing lipid A, is utilized. Encapsulation of RTS,S in liposomes containing monophosphoryl lipid A (MPL) resulted in a dose-dependent enhancement of the NANP-specific immunoglobulin G (IgG) antibody response compared to that of free RTS,S. The IgG1 and IgG2a subclasses predominated after immunization with RTS,S encapsulated in liposomes containing MPL. These results demonstrate that encapsulation of a lipid-containing particulate antigen, such as RTS, S, in liposomes containing lipid A can enhance both humoral and cellular immune responses.     

High-dose intravenous steroid pulse therapy in thyroid-associated ophthalmopathy

MIcrospheres containing diclofenac sodium (DS) were prepared using carboxymethylcellulose (CMC) as the main support material (1.0, 2.0, 3.0% (w/v)) and aluminum chloride as the crosslinker. Drug to polymer ratios of 1:1, 1:2 and 1:4 were used to obtain a range of microspheres. The microspheres were then coated with an enteric coating material, Eudragit S-100, efficiency, % yield value, particle sizes an in-vitro dissolution behaviour were investigated. The surface of the enteric coated microspheres seemed to be all covered with Eudragit S-100 from scanning electron microscopy observation. It was also observed that increasing the CMC concentration led to an increase in the encapsulation efficiency, % yield value and particle size and decreased the release rate. Eudragit S-100 coating did not significantly alter the size but the release rate was significantly lower even when the lower concentration solution was used.