Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Microspheres”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed1992

A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: embolic effect of cisplatin albumin microspheres using chitin and chitosan in dogs, and changes of cisplatin content in blood and tissue.

Hepatic artery of dogs was embolized with cisplatin (CDDP) albumin microspheres containing chitin and chitosan to investigate the in vivo CDDP release kinetics from CDDP albumin microspheres, the CDDP cumulative characteristics in the liver, and the influence of microsphere administration on hepatic tissue. Results showed that changes in blood CDDP content were dependent on CDDP albumin microsphere type and that release kinetics were better sustained when chitin was added to the microspheres or when the microspheres were treated with chitosan. In particular, the administration of CDDP in the chitin-containing CDDP chitosan albumin microspheres showed a blood CDDP content of approximately 0.26 micrograms Pt/ml 14 d after administration. The administration of chitin-containing or chitosan treated CDDP microspheres showed a CDDP content in the hepatic tissue of 0.14 to 0.23 micrograms Pt/g 28 d after administration. They also showed better control of CDDP release than those without chitin or chitosan treatment. No CDDP influence on hepatic tissue was observed. We conclude that, even in vivo, chitin and chitosan are effective embolic materials.

Animals↗
PubMed1992

Thermal characteristics of poly (DL-lactic acid) microspheres containing neurotensin analogue.

The thermal characteristics of poly (DL-lactic acid) (DL-PLA) microspheres containing a hexapeptide (NA: H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt) with neurotensin activity were investigated. PLA microspheres with a drug content of 1.5-11.0% were prepared by a novel o/w (oil-in-water) solvent evaporation method. Both DL-PLA and NA were amorphous in form, and an increase in heat capacity at glass transition temperature (Tg) of the polymer was observed in DL-PLA microspheres containing NA. The Tg of DL-PLA (PLA2000 bulk) was 307.8 K, while Tg of microspheres containing NA (content 6.0%) shifted to 321.2 K. The Tg of PLA2000 microspheres was found to increase with an increase in the content of NA, and its increasing tendency reached a plateau at an NA content of greater than 6%. The apparent activation energy of glass transition of PLA2000 bulk and the microspheres was calculated to be 86.3 and 99.3 kcal/mol, respectively. As a result of the release test after storage at 4 degrees C and 40 degrees C for 1 month, nearly the same release profiles of NA from PLA2000 microspheres were found. The release rate of NA after the initial release became slow after storage at 45 degrees C for 1 month. This may be attributed mainly to a decrease in surface area caused by the formation of agglomerates of PLA2000 microspheres under conditions near Tg.

Drug Storage↗
PubMed1992

[Effect of morphological properties on drug release from biodegradable microspheres].

The morphological properties of poly(beta-hydroxybutyric acid) (PHB) or poly(L-lactic acid) microspheres loading flomoxef sodium (FMOX) were investigated with regard to FMOX release. The release profiles of FMOX from the microspheres could be divided into two types, a sustained release type and a burst one. Two representative PHB microspheres, the release profiles of which were quite different from those of FMOX, were compared in detail from a morphological point of view. The shapes of their surfaces and sections were observed by using scanning electron microscopy (SEM), and FMOX distribution was analyzed by using electron probe microanalysis. The crystallinity of polymers was further measured by powder X-ray diffratometry. There was little difference in the FMOX distribution and their microscopic properties such as sphere size, specific surface area, shape of surface and section. In contrast, water penetration into the inside of the microspheres was found to be clearly different by use of cryogenic SEM. A significant difference was also observed in the crystallinity of polymers forming the microspheres. The release of FMOX from the microspheres was affected by the crystallinity of polymers forming the microspheres, and burst phenomena occurred in case the polymer was highly crystallized. It was speculated that the crystallization of polymer induced micro voids in the microspheres which functioned as channels for water penetration.

Biodegradation, Environmental↗
PubMed1994

[Pharmaceutical dosage form design of copoly (lactic/glycolic acid) microspheres. Mechanism of in vitro release of gentamicin].

The sustained release mechanism of gentamicin (GM) from lactic acid/glycolic acid copolymer (PLGA) microspheres was investigated. The terminal free carboxyl group of polymer was proved to be necessary for GM to be highly incorporated into microspheres by comparing interactions with GM and two types of polymers; free (ionized and non ionized) and the terminal esterified carboxyl group of polymer. The weight-average molecular weights (Mws) of component PLGAs of microspheres with an ionizable carboxyl group used here were approximately 4900 and 10000. The release pattern of GM was tested in phosphate buffered saline. The release rate of GM was dependent on the initial Mw and surface form. The GM release continued for 20 and 30 d from PLGA 4900- and PLGA10000-microspheres, respectively. The changes of total weight of microspheres tended to decrease with time, and the molecular weight distribution of PLGA gradually shifted to lower distribution, indicating a decrease in Mw. The changes and the shifts were dependent on the initial Mws of PLGAs but independent of their surface form. The half-times of wight loss of PLGA 4900- and PLGA10000-microspheres were about 10 and 20 d, respectively. From these results, the release profile of GM from PLGA microspheres was explained by the following three steps, i.e., 1) the release from the surface, 2) the relatively slow release caused by the obstruction of channels followed by the degradation of PLGA, 3) the release accompanied by the erosion of microspheres.

Biotransformation↗
PubMed2001

3D bone tissue engineered with bioactive microspheres in simulated microgravity.

Three-dimensional (3D) osteoblast cell cultures were obtained in rotating-wall vessels (RWV), simulating microgravity. Three types of bioactive microcarriers, specifically modified bioactive glass particles, bioceramic hollow microspheres, and biodegradable bioactive glass-polymer composite microspheres, were developed and used with osteoblasts. The surfaces of composite microspheres fully transformed into bone apatite after 2-wk immersion in simulated physiological fluid, which demonstrated their bone-bonding ability. The motion of microcarriers in RWVs was photographically recorded and numerically analyzed. The trajectories of hollow microspheres showed that they migrated and eventually stayed around at the central region of the RWV. At their surfaces, shear stresses were low. In contrast, solid glass or polymer particles moved toward and finally bounced off the outer wall of the RWVs. Cell culture studies in the RWV using bone marrow stromal cells showed that the cells attached to and formed 3D aggregates with the hollow microspheres. Extracellular matrix and mineralization were observed in the aggregates. Cell culture studies also confirmed the ability of the composite microspheres to support 3D bone-like tissue formation. These data suggest that the new hollow bioceramic microspheres and degradable composite microspheres can be used as microcarriers for 3D bone tissue engineering in microgravity. They also have potential applications as drug delivery systems.

Animals↗
PubMed1999

Improved protocol for a microsphere-adhesion assay on living tissue slices.

Here, we describe a simple microsphere-adhesion assay to characterize adhesive cues on living tissue slices, which we use to study pattern formation in neural tissue. This assay was developed by modifying a cell-adhesion assay on living tissue slices. We replaced dissociated cells by fluorescent microspheres and then coated the microspheres with isolated membranes from these cells. The membrane-coated microspheres were seeded on living tissue slices, and after a short incubation time, nonadherent microspheres were eliminated by washing. Then, the tissue slices with the adherent microspheres were analyzed using epifluorescence microscopy. As an example, it is shown that membrane-coated adherent microspheres were found to be distributed in a characteristic pattern on living slices of hippocampus, mimicking the adhesion pattern of dissociated living cells. The adhesion assay should be suitable to detect and to analyze adhesive cues on living slices of different tissues and, thus, might have numerous applications in tissue research and developmental studies. Here, we describe and discuss a detailed and improved protocol of the microsphere-adhesion assay.

Animals↗
PubMed1988

Deposition and retention patterns for 3-, 9-, and 15-micron latex microspheres inhaled by rats and guinea pigs.

This study was designed to determine the deposition patterns and fate of large particles inhaled by two species of small laboratory animals during nose breathing. Rats and guinea pigs inhaled 3-, 9-, or 15 micron polystyrene latex microspheres labeled with 46Sc. Approximately 1.4% and 0.55% of the initial internally deposited body burden of 3-micron microspheres was in the alveolar region of the respiratory tract of rats and guinea pigs, respectively. None of the 9- or 15-micron microspheres were detected in the alveolar regions of the rats or guinea pigs. Ninety-five to 99% of the deposited microspheres cleared from these animals with biological half-times of 0.5-1.0 day. Most of the cleared radioactivity was in the feces. Approximations for long-term biological half-times for alveolar retention of the 3-micron microspheres were 63 days for rats and 83 days for guinea pigs. About 1% of the initial lung burden of 3-micron microspheres was translocated from lung to lung-associated lymph nodes in both species; none of the 9- or 15-micron microspheres were detected in those lymph nodes. Small fractions of the microspheres initially deposited in the airways of the head were retained with biological clearance half-times ranging from 9 to 350 days. Results from this study do not allow projections for deposition and retention patterns for similar particles inhaled by humans. Such projections must come from studies with humans, or from studies with animal species having deposition patterns for inhaled materials more comparable to those of humans.

Air Pollutants↗
PubMedDate not supplied

Effect of encapsulation of chloramphenicol in albumin microspheres on its in vitro transfer across the human placenta.

The possibility of reducing drug transfer across the placenta was tested in two of our previous studies. The aim of those studies was to demonstrate an alternative method of drug application during pregnancy which we think would yield a dual benefit, i.e. protecting the foetus from the harmful effects of drugs while curing the mother. The present study was planned as a continuation of the testing of the same idea and we tried to see the effect of albumin microsphere encapsulation of chloramphenicol on its transfer across the human placenta in vitro. Microspheres containing chloramphenicol were prepared according to the method previously described. The mean per cent encapsulation of chloramphenicol in albumin microspheres was found to be 42 +/- 4.3 per cent (n = 5) and the mean size of the albumin microspheres was 3.08 +/- 0.6 mm. In vitro stability of the drug-carrying microspheres was measured by dialysing them at 37 degrees C for 24 h. Chloramphenicol was released from the microspheres gradually leaving about 50 per cent of the entrapped drug in the microspheres after 1.5 h. About 20 per cent of the chloramphenicol was retained in the microspheres at 24 h postincubation. The persistence of the antibacterial effect of the released chloramphenicol is confirmed by antibiogramme tests. In the perfusions the initial free drug concentration was kept at 100 mg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMedDate not supplied

pH-dependent microspheres from modified soybean protein hydrolysate.

Soybean hydrolysate is a hydrophilic mixture of amino acids and low molecular peptides which are soluble over the whole pH range. Chemical modification of soybean hydrolysate with aromatic acyl chlorides resulted in a product that yielded pH-dependent microspheres. Investigation into the physiochemical properties of the microsphere forming material indicated that acylation had alerted the hydrophobic/hydrophilic ratio as evidenced by an increased column retention time on reverse phase HPLC. This was further confirmed by analysis of the amino acid composition of the modified material. The data indicated that the hydrophobic/hydrophilic ratio and low molecular were critical factors in the formation of this supramolecular complex. An estimation based on sedimentation rate revealed an average molecular weight of these microspheres as 10(7)-10(8) Daltons. Light scattering experiments indicated that the microspheres have discrete chambers in the interior. Included among the properties of the microspheres that have been determined are the pH range of the phase transition, size distribution and zeta-potential. The physiochemical characteristics of the microspheres prepared from modified soybean protein are similar to the microsphere forming material produced by thermal condensation of amino acids. Formation of microspheres in solution containing either porcine insulin or salmon calcitonin resulted in the encapsulation of nearly 60% of the dissolved proteins. Oral gavage of encapsulated porcine insulin or salmon calcitonin into the stomach of rats resulted in significant titers of either protein in the systematic circulation.

Amino Acids↗
PubMedDate not supplied

Properties of multiphase microspheres of poly(dl-lactic acid) or poly(dl-lactic-co-glycolic acid) produced by mechanical agitation, sonication, or potentiometric dispersion.

The effect of processing techniques on the molecular weight of the polymer in biodegradable microspheres of poly(dl-lactic acid) (PLA) and poly(dl-lactic-co-glycolic acid) (PLGA) was investigated. Multiphase microspheres were produced by conventional agitation, potentiometric dispersion, or sonication. Gel permeation chromatography was used to determine the molecular weight of the polymer before and after processing. Polymer in microspheres of PLA produced by sonication experienced a 21% decrease in molecular weight of the polymer after 90 s of sonication, while microspheres made by potentiometric dispersion or mechanical agitation exhibited insignificant changes in molecular weight. Microspheres produced by potentiometric dispersion were found to have a more narrow particle size distribution compared to the other methods. A decrease in the internal diameter of the infusion tube used to produce multiphase microspheres by the potentiometric dispersion method was found to decrease the mean particle size of the resultant microspheres. Two surfactants were investigated at varied levels for utilization in the continuous phase, and particle size analysis revealed that increased surfactant levels caused an increase in the mean particle size of microspheres containing BSA produced by potentiometric dispersion. This phenomenon was attributed to an increase in conductivity of the continuous phase as the surfactant level was increased.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

In vitro analysis of the release of incorporated agents from sodium caseinate microspheres.

Drug loaded microspheres were successfully prepared using the dairy protein, sodium caseinate (SC), as the carrier material and containing hydrochlorothiazide, eosin, patent blue violet and sodium salicylate. The morphology of the microspheres varied depending on the incorporated material. Release of the incorporated agents from these systems was rapid with over 90% release in each case within 1 h. Further drug release occurred at a greatly reduced rate with a certain proportion of the drug loading appearing to be indefinitely entrapped within some of the microspheres. The drug release profiles were poorly described using the square root of time and Sinclair and Peppas equations but were well described by a biexponential equation. Analysis of the parameter estimates from the biexponential equation indicated that the initial rapid release phase was essentially completed within 5 min for all but the eosin microsphere systems and this timeframe was of the same order of magnitude as that found for the initial swelling of these microsphere systems as analysed by swelling studies using optical microscopy. Considering both the swelling study and the results from the release experiments, it seems likely that addition of SC microspheres to aqueous media results in immediate hydration and swelling. This process facilitates the rapid diffusional passage of water soluble drugs through the swollen and hydrated microsphere matrix, with drug release occurring almost unhindered unless other factors favour the retention of the incorporated agent with the microsphere.

Caseins↗
PubMedDate not supplied

Effect of magnesium stearate on chitosan microspheres prepared by an emulsification-coacervation technique.

Chitosan microspheres were prepared using an emulsification-coacervation technique. The w/o emulsion comprised a mixture of light and heavy liquid paraffins containing sodium dioctyl sulphosuccinate as the oil phase and chitosan solution as the aqueous phase. Pentasodium tripolyphosphate was included as a counterion. The chitosan microspheres obtained showed a high degree of aggregation. This was markedly reduced, by the incorporation of magnesium stearate in the disperse phase. The resultant microspheres were then discrete, spherical with smooth surfaces. Additionally, with an increasing magnesium stearate content, larger-sized microspheres were produced. The DSC analysis data suggested that the magnesium stearate was converted to stearic acid during the preparation process. Chitosan microspheres containing propranolol hydrochloride were similarly prepared, but their surface was convoluted and their shape not well defined. Unlike the microspheres without drug, the size of the drug-loaded microspheres decreased with increasing magnesium stearate content. The release of propranolol hydrochloride from the microspheres was fast, irrespective of the content of magnesium stearate. Drug encapsulation efficiency was enhanced when a greater amount of magnesium stearate was used.

Animals↗
PubMedDate not supplied

Effects of poly(vinylpyrrolidone) and ethylcellulose on alginate microspheres prepared by emulsification.

Calcium alginate microspheres were prepared by an emulsification process. The effects of two co-polymers, namely poly(vinylpyrrolidone) and ethylcellulose, on the properties of the microspheres were studied. Microspheres prepared with and without poly(vinylpyrrolidone) were spherical and discrete. The microspheres containing poly(vinylpyrrolidone) exhibited a better flow property but the drug content was lower and the drug release rate higher. The method of incorporating poly(vinylpyrrolidone) was found to (significantly) affect the size distribution and drug content of the microspheres. Ethylcellulose produced marked aggregation of the microspheres which also showed a lower drug content, but a slower drug release. The retardation in drug release was attributed to the formation of aggregated microspheres with a less permeable matrix. The addition of triethyl citrate, which is a water-soluble plasticizer, was found to increase the rate of drug release while the use of a higher viscosity grade of ethylcellulose produced the opposite effect. Ethylcellulose improved the flowability of the microspheres to a greater extent than poly(vinylpyrrolidone).

Alginates↗
PubMedDate not supplied

Development and characterization of buoyant theophylline microspheres with near zero order release kinetics.

The objective of this study was to prepare floating theophylline microspheres with zero order release profiles for use as buoyant reservoirs with increased retention time in the stomach. The microspheres were prepared by a modified emulsion-solvent evaporation method using a polymer mixture of cellulose acetate butyrate and Eudragit RL 100 (1:1). The drug-polymer dispersions were pressurized under carbon dioxide gas which dissolved in the drug-polymer dispersions and formed bubbles upon the release of the pressure. Some of the bubbles were entrapped in the dispersed drug-polymer droplets and eventually formed internal cavities in the microspheres. The resulting microspheres were characterized for size distribution, morphology, density, drug-polymer content, buoyant capacity and drug release behaviour. The microspheres were spherical with relatively smooth surfaces with round hollow cavities. The microspheres and low densities (less than 1 g/cm3) and remained floating for more than 24 h in pH 1.2 and 7.5 buffers. The dissolution profiles of the floating theophylline microspheres showed near zero order kinetics and sustained release in both pH 1.2 and 7.5 buffers. Modified microspheres processed with the addition of 2% w/v polysorbate 80 to the internal phase had smaller sizes, lower densities and faster drug release compared with those without the addition of the surfactant.

Cellulose↗
PubMedDate not supplied

Preparation and characterization of melatonin-loaded stearyl alcohol microspheres.

A sustained release dosage form which delivers melatonin (MT), a pineal hormone, is of clinical value because of the short half-life of MT, for those who have a disordered circadian rhythm. The purpose of this study was to prepare MT-loaded microspheres by the emulsion melting/cooling method using stearyl alcohol (SA) and also dual walled chitosan and sodium alginate beads, and to evaluate the release characteristics in simulated gastric and intestinal fluid. The MT-loaded microspheres were spherical, ranging in diameter from about 250-750 microm. When polyethylene glycol 4000 (PEG), as a water-soluble or aluminium tristearate (AT), as a water-insoluble additive, was incorporated, the surface roughness was further reduced resulting in a smooth matrix structure. The dual walled chitosan and sodium alginate beads entrapping small MT-loaded microspheres were not spherical in structure. As the additives incorporated into SA microspheres increased, the drug content decreased. The release profiles of the MT-loaded microspheres were independent of pH. When the melted SA solution was cooled rapidly in 10 min to 25 degrees C, the drug content increased but the release rate of MT-loaded microspheres decreased. The release rate of drug decreased as the amount of SA increased but an increase of agitation speed and amount of AT and PEG resulted in increased release rates. The release rate of drug from dual walled chitosan beads increased slightly but was retarded in the case of dual walled alginate beads when compared to MT-loaded microspheres. The emulsion melting/cooling method used to prepare MT-loaded microspheres using SA is simple and inexpensive, and may provide an alternative for the preparation of an oral sustained release dosage form of MT without using harmful organic solvents. The dual walled chitosan and sodium alginate beads may also provide a convenient way to control the release of drugs.

Alginates↗
PubMed1998

Development of a sustained-release biodegradable polymer delivery system for site-specific delivery of oligonucleotides: characterization of P(LA-GA) copolymer microspheres in vitro.

Development of a Sustained-Release Biodegradable Polymer Delivery System for Site-Specific Delivery of Oligonucleotides: Characterization of P(LA-GA) Copolymer Microspheres In Vitro Antisense oligodeoxynucleotides (ODNs) can selectively inhibit individual gene expression provided they gain access to and remain stable at the target site for a sufficient period of time. Biodegradable sustained-release delivery systems may facilitate site-specific delivery and also prevent degradation of ODNs by nucleases whilst delivering the nucleic acid in a controlled manner to the desired site of action. In this study, we have characterized biodegradable poly (lactide-co-glycolide) (P(LA-GA)) 50:50 microspheres for the potential delivery of antisense oligonucleotides in vivo. Phosphodiester (PO) oligonucleotides complementary to either c-myc proto-oncogene or the tat gene in HIV-RNA were adequately incorporated within P(LA-GA) microspheres with entrapment efficiencies up to 60% depending on particles size. In vitro release profiles of antisense nucleic acids from 10-20 microm size microspheres over 56 days in physiological buffer were triphasic. Profiles were characterised by an initial burst effect during the first 48 hours (phase 1) of release followed by a more sustained release (phase 2) with an additional increased release (phase 3) being observed after 25 days which corresponded with bulk degradation of the copolymer matrix. The release profiles were influenced by microsphere size, copolymer molecular weight, ODN loading, ODN length and by the pH of release medium used. The serum stability of PO ODNs was significantly improved when entrapped within P(LA-GA) microspheres and the hybridization capability, as assessed by duplex melting (Tm) measurements, of released ODN was not impaired by the double-emulsion microsphere fabrication procedure used. Thus, P(LA-GA) microspheres appear to be promising candidates for improving site-specific delivery profiles for ODNs and are worthy of further evaluation in vivo.

Base Sequence↗
PubMed2000

Polycation-coated polyanion microspheres of urease for urea hydrolysis.

Urease (EC 3.5.1.5) was immobilized within polyanionic carboxymethylcellulose/alginate (CMC/Alg) microspheres coated with a cationic polysaccharide, chitosan (C). Coating with chitosan improved the mechanically durability of the polyanionic microspheres, as well as increased enzyme immobilization yield [approximately 0.4 mg.mL-1 gel]. The effects of chitosan coating and CMC/Alg ratio on the water uptake and spherical morphology of the microspheres were investigated. The optimal pH of urease was not extensively affected by the immobilization procedure. However, the optimal temperature of urease activity increased upto 60 and 65 degrees C within CMC/Alg and C(CMC/Alg) microspheres, respectively, while the optimum for the free enzyme was 50 degrees C. The half life (t1/2) and deactivation rate constant (kd) of free urease were 79 min and 8.77 x 10(-3) min-1, respectively, whilst the t1/2 and kd values of urease within polyanion and polycation-coated polyanion microspheres were 142 min and 4.88 x 10(-3).min-1, and 179 min and 3.87 x 10(-3).min-1, at 80 degrees C, respectively. While the activation energy of the hydrolysis reaction of free urease was found to be 11.86 kJ.M-1.dm-3, it increased to 18.91 and 20.02 kJ.M-1.dm-3, for the immobilized urease within CMC/Alg and C(CMC/Alg) microspheres, respectively. The free enzyme exhibited K(m) and Vmax values of 2.85 mM.dm-3 and 31.9 mM.dm-3.s-1.g-1p-1, respectively, whilst the K(m) and Vmax for urease within polyanion and polycation-coated polyanion microspheres were 3.94 mM.dm-3 and 73.4 mM.dm-3.s-1.g-1.p-1, and 4.22 mM.dm-3 and 81.4 mM.dm-3.s-1.g-1.p-1, in the same order. C(CMC/Alg) microspheres showed a nearly stable urease activity of around 80-85% of the initial maximum activity, after the first 100 minutes.

Alginates↗
PubMed2002

Injection of chemotherapeutic microspheres and glioma. III: Parameters to optimize efficacy.

Injectable microspheres may provide a means of providing local, sustained exposure of glioma to chemotherapeutics to improve patient survival. Using a rodent model of surgically resected glioma, we previously demonstrated that direct injections of chemotherapeutic microspheres into the tissue surrounding a resection cavity provide superior survival effects over injections of the same microspheres directly into the surgical cavity. The present experiments extended this novel observation by exploring several parameters related to the use of intraparenchymal injections of chemotherapeutic microspheres to treat glioma. Using a rat model of resected glioma, several principles regarding the use of local sustained release carboplatin microspheres were established. First, an inverted U dose-response was observed, wherein further dose escalation beyond the optimal dose was not efficacious and indeed produced significant local toxicity. Second, it was necessary to expose approximately 40% of the tumor margin to sustained release carboplatin in order to increase survival in this model. Survival was not enhanced when the proportion of the tumor margin exposed to carboplatin was only 20%. Third, the distribution of the chemotherapeutic microsphere injections along the tumor perimeter was shown to be important, requiring that the entire perimeter be proportionately exposed to the chemotherapeutic agent. Together, these data continue to support the development of chemotherapeutic microspheres for treating glioma. However, they also caution that a number of fundamental parameters can profoundly influence the efficacy that might be expected from local sustained delivery. Careful attention to these principles is not only required if chemotherapeutic microspheres are to be used efficaciously, but these principles should provide a foundation to further optimize the potential of this and other polymeric delivery systems under development for local, intraparenchymal drug delivery to glioma.

Animals↗