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At least 1,225 records · Page 68Linked to original sources
PubMed2000

Influence of process parameters on the protein stability encapsulated in poly-DL-lactide-poly(ethylene glycol) microspheres.

Glucose oxidase (GOD) has been encapsulated as a model protein within poly-DL-lactide-poly(ethylene glycol) (PELA) microspheres to evaluate the activity retention during microencapsulation process. This paper was aimed to investigate the effect of process parameters, such as the preparation method, the used matrix polymer with different compositions, the solvent system and the addition of stabilizer on the structural integrity and activity retention of encapsulated protein. The stability of the protein released during in vitro assay was also assessed. The obtained results showed that the solvent extraction/evaporation method based on the formation of double emulsion w(1)/o/w(2) benefited the activity retention compared with the phase separation method based on the formation of w/o(1)/o(2). And in the emulsion-evaporation system most of the protein activity was lost during the first emulsification procedure to form primary emulsion w(1)/o (ca. 28%) and the second emulsification procedure to form the double emulsion w(1)/o/w(2) (ca. 20%), in contrast to other processes occurring during microspheres preparation. The matrix polymer and the solvent system in the oil phase had an impressive impact on the activity retention, while the addition of gelatin in the internal aqueous phase resulted in no major reduction of activity loss. GOD release from PELA microspheres exhibited a triphasic profile, that is, the initial burst release during the first day, the gradual release over about 1 month, and then the second burst release. The encapsulation of GOD in PELA microspheres was effective in reducing its specific activity loss. Sixty-seven per cent of the initial specific activity retention was detected for the released GOD from microspheres formulation during 1 week of incubation, but nearly all the activity was lost for GOD in solution incubated under the same condition. SDS-PAGE results showed that, although the activity loss was detected, no rough changes of molecular weight of GOD was observed during encapsulation procedure and the initial days of incubation into the in vitro release medium.

Absorbable Implants↗
PubMed2000

Comparison of poly(acryl starch) and poly(lactide-co-glycolide) microspheres as drug delivery system for a rotavirus vaccine.

Drug delivery systems allowing controlled release of antigen are of particular interest in the development of vaccines. We have compared poly(acrylic starch) microspheres (PAS) and poly(lactide-co-glycolide) microspheres (PLG) as drug delivery systems for a rotavirus vaccine. The polymers are both biodegradable but have different degradation mechanisms and antigen release profiles. PAS are enzymatically degraded and have a continuous fast antigen release rate compared to the hydrolytically degraded PLG which release the incorporated antigen in a pulsatile manner. In this study mice were immunised intramuscularly and orally on three occasions with formalin-inactivated rotavirus (FRRV) incorporated in PAS and PLG and with FFRV alone. Serum and faeces samples were collected and analysed by ELISA for rotavirus specific IgG and IgA antibodies. A neutralising assay was also conducted on both serum and faeces antibodies. The two different polymer drug delivery systems induced different immune responses depending on administration route. PAS elicited significant antibody levels and neutralising effect after oral administration while PLG showed high antibody levels after intramuscular administration. The immune response appears to be dependent on the differences in antigen release and degradation mechanism for the two polymer systems.

Animals↗
PubMed2001

In vitro degradation and release profiles for poly-dl-lactide-poly(ethylene glycol) microspheres containing human serum albumin.

Poly-dl-lactide-poly(ethylene glycol) (PELA) block copolymers containing same the content (10%) of polyethylene glycol (PEG) were synthesized with five different molecular weight of PEG by ring-opening polymerization. PELA microspheres containing human serum albumin (HSA) were elaborated by solvent extraction method based on the formation of double w/o/w emulsion. In vitro matrix degradation and protein release of these microspheres were performed in phosphate-buffered saline (PBS) (154 mM, pH 7.43). The degradation profiles were characterized by measuring the loss of microspheres mass, the decrease of polymer intrinsic viscosity, the decrease of pH value of degradation medium, the reduction of polymer number-average molecular weight (M(n)) and the change of molecular weight polydispersity (M(w)/M(n)). The release profiles were investigated from the measurement of protein presented in the release medium at various intervals. It showed that the matrix degradation and protein release profiles were highly polymer-dependent. The extent of burst release in the initial protein release increased with the decrease of molecular weight of PELA copolymer. It is suggested that these matrix polymers may be optimized as carriers in protein (antigen) delivery system for different purposes.

Biocompatible Materials↗
PubMed2001

Thermoreversible gelation of biodegradable poly(epsilon-caprolactone) and poly(ethylene glycol) multiblock copolymers in aqueous solutions.

The multiblock copolymers composed of poly(ethylene glycol)s (PEGs) and biodegradable poly(epsilon-caprolactone)s (PCLs) were synthesized through one-step condensation copolymerization with hexamethylene diisocyanate (HDI) as a coupling agent. The typical phase diagram of these multiblock copolymers in aqueous solution displayed a critical gel concentration (CGC) and an upper phase-transition temperature, which were mainly determined by the PEG/PCL block ratio, the PEG or PCL block lengths and the molecular weight. With decreasing PEG/PCL block ratio, the CGC decreased with an elevated sol-gel transition temperature on account of the enhanced hydrophobicity. The HDI/Diols ratio was used to control the molecular weight. At high molecular weights, the CGC decreased, related to the enhanced aggregation of PCL blocks and physical crosslinkage between PCL block domains due to the increased number of PCL blocks in each molecule. For the sample containing the long PCL(2000) block (M(n), 2000), the CGC dropped dramatically due to the high hydrophobicity and the poor compatibility between PCL and PEG. The dynamic phase transition process was observed by combining optical microscopy (OM) and differential scanning calorimetry (DSC) in a certain heating/cooling rate. Finally, a possible phase separation-induced gelation mechanism is suggested.

Biodegradation, Environmental↗
PubMed2001

DNA transfection using linear poly(ethylenimine) prepared by controlled acid hydrolysis of poly(2-ethyl-2-oxazoline).

A series of linear poly(ethylenimine) (L-PEI) containing varying amounts of cationic charge density in its backbone was produced by controlled hydrolysis of poly(2-ethyl-2-oxazoline) (PEtOz) for using as a nonviral DNA transfection agent. The effects of cationic charge density and molecular weight of the L-PEI on the cytotoxicity and transfection efficiency were studied. The efficiency of transfection was monitored by using a luciferase reporter gene system. Gel retardation assay and dynamic light scattering (DLS) showed that the condensation capacity of L-PEI was suitable for transfection. Highly compacted L-PEI/DNA complex ( approximately 150 nm) was obtained with a surface charge value of around +28.4 mV. Cell cytotoxicity was affected to a great extent by the hydrolysis percent of L-PEI as well as by the molecular weight. Transfection efficiency of luciferase plasmid DNA against NIH 3T3 fibroblast was largely dependent upon the hydrolysis percent (charge density) in the polymer backbone and the molecular weight of the L-PEI, but independent of the total amount of cationic charges used for DNA condensation. L-PEI with a hydrolysis percent of 88.0% exhibited comparable transfection efficiency to that of commonly used branched PEI.

3T3 Cells↗
PubMed2001

Protein release microparticles based on the blend of poly(D,L-lactic-co-glycolic acid) and oligo-ethylene glycol grafted poly(L-lactide).

Bovine serum albumin (BSA), a model protein drug, was encapsulated with a microparticle based on the blend of poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactide)-g-oligo(ethylene glycol) (PLLA-g-oligoEG). Effects of PLLA-g-oligoEG in the blend on degradation, characteristic properties, and release behavior of the microparticle were studied. Drug loading efficiency increased with increase in the graft frequency of oligoEG in the graft copolymer in the blend. The release of BSA was found to be more efficient for microparticles based on the blend than on the PLGA, which is due to the faster protein diffusion through the swollen phase of the hydrogel-like structure. The microparticles based on the blend showed a slower degradation and a lower pH shift compared to that of PLGA.

Calorimetry, Differential Scanning↗
PubMed2001

Long-circulating poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles with modulated surface charge.

Reactive polymeric micelles consisting of an alpha-acetal-poly(ethylene glycol)-poly(D,L-lactide) block copolymer (acetal-PEG-PDLLA) with a narrow size distribution were prepared in this study to conjugate small peptidyl ligands, tyrosine (Tyr) and tyrosyl-glutamic acid (Tyr-Glu), through reductive amination after converting the alpha-acetal group to an aldehyde group, allowing modulation of the surface charge of the micelles from neutral (Tyr-) to anionic (Tyr-Glu-). Both of these micelles showed a significantly long circulating time in the blood compartment with 25% of injected dose still circulating even at 24 h. Further, an appreciably lowered uptake into the liver and spleen was demonstrated for the anionic Tyr-Glu-conjugated PEG-PDLLA micelle compared with a neutral Tyr-conjugated micelle, suggesting a substantial role of the slight anionic charge on the micelle surface in avoiding non-specific organ uptake. Stability of the micelle form in the blood compartment was directly observed for the Tyr-PEG-PDLLA micelle by a gel filtration assay of a plasma sample collected from the micelle-injected mice at 24 h. These results demonstrated that a surface-modulated PEG-PDLLA micelle with a suitable size and a narrowly distributed nature has promising potential as a long-circulating carrier system with desirable biocompatibility and biofunctionality.

Drug Carriers↗
PubMed2001

Micelles self-assembled from poly(ethylene oxide)-block-poly(N-hexyl stearate L-aspartamide) by a solvent evaporation method: effect on the solubilization and haemolytic activity of amphotericin B.

The goal of this study was to assess a solvent evaporation method for the encapsulation of amphotericin B (AmB) in poly(ethylene oxide)-block-poly(N-hexyl stearate L-aspartamide) (PEO-b-PHSA) micelles. By the solvent evaporation method, PEO-b-PHSA self-assembled into small spherical micelles with a high AmB content based on transmission electron microscopy, size exclusion chromatography and absorption spectroscopy. The encapsulation of AmB was slightly better than an earlier method based on dialysis. Importantly, AmB in PEO-b-PHSA micelles encapsulated by the solvent evaporation method was non-haemolytic at 15 microg/ml, whereas AmB in PEO-b-PHSA micelles encapsulated by the dialysis method caused 50% haemolysis at the level of 3.8 microg/ml, and AmB itself caused 100% haemolysis at 1.0 microg/ml. Thus, PEO-b-PHSA micelles could effectively encapsulate AmB, increase the overall water solubility of AmB and reduce the toxicity of the membrane-acting drug, particularly by a solvent evaporation method.

Amphotericin B↗
PubMed2002

Artery wall binding peptide-poly(ethylene glycol)-grafted-poly(L-lysine)-based gene delivery to artery wall cells.

Artery wall binding peptide (AWBP; Cys-Gly-Arg-Ala-Leu-Val-Asp-Thr-Leu-Lys-Phe-Val-Thr-Gln-Ala-Glu-Gly-Ala-Lys), a specific targeting peptide, was conjugated to poly(ethylene glycol)-grafted-poly(L-lysine) (PEG-g-PLL) to enhance the gene transfer to artery wall cells. AWBP-PEG-PLL was synthesized by the reaction between the vinylsulfone group of PEG-g-PLL and the thiol group of cysteine in AWBP. 1H-NMR analysis confirmed the composition of the obtained polymer and indicated that four mol of AWBP were reacted to one mole of VS-PEG-PLL. The particles of AWBP-PEG-PLL/pDNA complexes were determined spherical with a size of approximately 100 nm by dynamic light scattering (DLS) and atomic force microscopy (AFM). Agarose gel retardation assay indicated that AWBP-PEG-PLL was able to condense plasmid DNA and reach complete complexation at and above a charge ratio 1/1 (+/-). Transfection efficiency of AWBP-PEG-PLL/pDNA complexes was 150-180 times higher than that of control systems, such as PEG-g-PLL/pDNA and PLL/pDNA, in both bovine aorta endothelial cells and smooth muscle cells. Luciferase activities of AWBP-PEG-PLL depended on the amount of free AWBP, while those of the control carriers such as PLL and PEG-g-PLL were not affected by free AWBP. These results supported that gene transfer of AWBP-PEG-PLL/pDNA complexes to bovine aorta wall cells was mediated by specific artery wall cell receptor-mediated endocytosis.

Amino Acid Sequence↗
PubMed2002

The effect of fatty acid substitution on the in vitro release of amphotericin B from micelles composed of poly(ethylene oxide)-block-poly(N-hexyl stearate-L-aspartamide).

The effect of fatty acid substitution on the in vitro release of amphotericin B (AmB) from micelles composed of poly(ethylene oxide)-block-poly[N-(6-hexyl stearate)-L-aspartamide] (PEO-b-PHSA) was investigated. PEO-b-PHSA at 11, 50 and 70% of stearic acid substitution self assembled into micelles that effectively encapsulate AmB by solvent evaporation and dialysis methods. The sustained release of AmB from PEO-b-PHSA micelles was evidenced, by measuring the transfer of the drug to lipid vesicles [dipalmitoyl phosphatidylcholine:cholesterol:dimyristoyl phosphatidyglycerol (3:1:0.25)]. The release of AmB for PEO-b-PHSA micelles was markedly influenced by the degree of fatty acid substitution--as it increased, the release of AmB slowed. Accordingly, drug release was found to correlate with haemolysis induced by AmB encapsulated in PEO-b-PHSA micelles. At 11% stearic acid substitution, encapsulation of AmB had little effect on the drug's ability to induce untoward haemolysis. In contrast, AmB stably encapsulated in PEO-b-PHSA micelles at 50 and 70% caused no hemolysis up to 20 microg/ml. Lastly, PEO-b-PHSA micelles at 50 and 70% were able to elute entirely as micelles during size-exclusion chromatography, indicating their stability toward dissociation after dilution. The results point to a nanoscopic drug depot that may release AmB at controlled rates.

Amphotericin B↗
PubMed2002

Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend.

Electrospun fiber mats are explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. The mats were made either from poly(lactic acid) (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two. The fibers were electrospun from chloroform solutions containing a small amount of methanol to solubilize the drug. The release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV-VIS spectroscopy. Release profiles from the electrospun mats were compared to a commercially available drug delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast films of the various formulations.

Anti-Bacterial Agents↗
PubMed2002

Poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers.

Poly(lactic-co-glycolic acid) (PLGA)-grafted poly(L-lysine) (PLL) (PLL-g-PLGA) was synthesized to demonstrate its micelle-forming property in an aqueous solution. The micelles were used as a gene delivery carrier. The hydrodynamic diameter of PLL-g-PLGA micelles in an aqueous solution was ca. 149 nm with a narrow size distribution. Critical micelle concentration (cmc) was 9.6 mg/l. The PLL-g-PLGA micelles could be used to produce compact nanoparticulate complexes with plasmid DNA, which could efficiently protect the complexed DNA from enzymatic degradation by DNase I. The micelle/DNA complexes had highly compacted structure sized between 200-300 nm with a positive surface charge value. The PLL-g-PLGA micelles exhibited much higher transfection efficiency with lower cytotoxicity than PLL. Here, we demonstrated that biodegradable and cationic PLL-g-PLGA micelles could be used as an effective DNA condensation carrier for gene delivery system.

3T3 Cells↗
PubMed2002

Temperature-related change in the properties relevant to drug delivery of poly(ethylene glycol)-poly(D,L-lactide) block copolymer micelles in aqueous milieu.

The block copolymers of poly(ethylene glycol) and poly(D,L-lactide) (PEG-PDLLA), the latter having a glass transition temperature (T(g)) around the physiological condition, was self-assembled into polymer micelles with a narrow and unimodal distribution in aqueous milieu either by dialysis or by the ultrasonication-aided dispersion method. The 1H NMR measurement of the PEG-PDLLA micelles in D(2)O revealed a gradual increase in the chain mobility of PDLLA segment in the core of the micelles at a temperature range above the T(g) of PDLLA. The critical association concentration (c.a.c.) of the PEG-PDLLA micelles was determined at various temperatures (25-55 degrees C) using pyrene as a probe to monitor the change in the polarity of the microenvironment in the micelle. An Arrhenius plot of the c.a.c. (ln(c.a.c.) versus 1/T) exhibited a break near T(g) of PDLLA. In sharp contrast with the linear decrease in ln(c.a.c.) versus 1/T in the region above the T(g), there was observed an almost constant c.a.c. (7-8 mg/l) regardless of the temperature change below the T(g). Furthermore, the chain exchange reaction between micelles was investigated based on the migration of the end-tagged block copolymers (alpha-lactosyl-PEG-PDLLA and omega-pyrenyl-PEG-PDLLA). The change in the binding affinity of the fluorescent micelles toward the RCA-1 lectin immobilized column was monitored with time to estimate the chain exchange. Consequently, appreciable acceleration in the chain exchange rate was revealed by increasing the surrounding temperature indicating the core mobility to be a substantial factor for inter-micellar chain migration. These results indicate that the engineering of the thermal characteristics of the core-forming segment of the block copolymer should be one of the crucial factors for optimizing the properties of the polymer micelles used for drug delivery.

Deuterium Oxide↗
PubMed2003

Polymeric micelles of poly(2-ethyl-2-oxazoline)-block-poly(epsilon-caprolactone) copolymer as a carrier for paclitaxel.

Polymeric micelles based on amphiphilic block copolymers of poly(2-ethyl-2-oxazoline) (PEtOz) and poly(epsilon -caprolactone) (PCL) were prepared in an aqueous phase. The loading of paclitaxel into PEtOz-PCL micelles was confirmed by 1H-NMR spectra. Paclitaxel was efficiently loaded into PEtOz-PCL micelles using dialysis method, and the loading content of paclitaxel in micelles was in the range 0.5-7.6 wt.% depending on the block composition of block copolymers, organic solvent used in the dialysis, and feed weight ratio of paclitaxel to block copolymer. The higher the content of hydrophobic block in the block copolymers, the higher the loading efficiency of micelles for paclitaxel. When acetonitrile was used as solvent, a higher drug loading efficiency was obtained than with THF. The loading efficiency decreased with increasing feed weight ratio of paclitaxel to block copolymer from 0.1:1 to 0.2:1. The hydrodynamic diameters of paclitaxel-loaded micelles were in the range 18.3-23.4 nm with narrow size distribution. The hemolysis test of PEtOz-PCL performed in vitro indicated that the toxicity of PEtOz-PCLs to lipid membrane was not significant compared with Tween 80, and was comparable to that observed with Cremophore EL. The proliferation inhibition activity of paclitaxel-loaded micelles for KB human epidermoid carcinoma cells was also evaluated in vitro. Paclitaxel-entrapped polymeric micelles exhibited comparable activity to that observed with Cremophore EL-based paclitaxel formulations in inhibiting the growth of KB cells.

Animals↗
PubMed1998

Influence of the microencapsulation method and peptide loading on poly(lactic acid) and poly(lactic-co-glycolic acid) degradation during in vitro testing.

Three methods were used, namely spray drying, w/o/w solvent evaporation and the aerosol solvent extraction system (ASES), for the preparation of microparticles having the same size range, to study the influence of the preparation method on polymer degradation in vitro (PBS, 37 degrees C, one month). The following five polymers of the biodegradable poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) group were selected: L-PLA, MW 81 200; DL-PLGA 75:25, MW 64-300; DL-PLGA 50:50 MW 52 600; DL-PLGA 50:50 MW 14 500, AND DL-PLGA 50:50, MW 3400, to prepare drug-free and drug-loaded microparticles. Tetracosactide was selected as model peptide. When microparticles were prepared by solvent evaporation, the mean diameter and, more markedly, the drug encapsulation efficiency tended to decrease when decreasing the molecular weight and increasing the proportion of glycolic acid in the polymer. In contrast, no direct influence of the polymer nature on these parameters was observed in spray dried microparticles. Polymer degradation was heterogenous in L-PLA and DL-PLGA 75:25 microparticles and was not influenced by the presence of the drug at a nominal loading of 1% (w/w), when prepared by the three methods (note that with ASES, only L-PLA could be used for microencapsulation). In batches made of DL-PLGA 50:50 MW 52 600, the degradation rate decreased slightly when increasing the drug loading. Only in the case of DL-PLGA 50:50 MW 14 500, the polymer degradation rate for spray dried microparticles was higher compared to that for microparticles prepared by the w/o/w solvent evaporation method. Generally, the degradation rates of the different microparticles followed the expected order: L-PLA<DL-PLGA 75:50<DL-PLGA 50:50(Mw 52 600)<DLPLGA 50:50 (a mixture of MW 52 600 and MW 3400). Polymer degradation was homogenous in DL-PLGA 50:50 microparticles. Decreasing the molecular weight of DL-PLGA 50:50 from 52 600 to 14 500 did not result in accelerated polymer degradation.

Aerosols↗
PubMed1998

In vitro release of trypanocidal drugs from biodegradable implants based on poly(epsilon-caprolactone) and poly(D,L-lactide).

In this study, commercial available poly(epsilon-caprolactone)s and poly(d,l-lactide)s of different molecular masses were used. Slow release devices (SRD) were obtained as rods of suitable diameters by extrusion of polymer-drug mixtures (75:25, w/w) which were prepared by the solution casting method. The rods were coated by dipping them in a methylene chloride solution of the core polymer. The in vitro release of the selected drugs, isometamidium chloride (IMM) and ethidium bromide (EtBr) from such rods was carried out in phosphate buffer (PB) pH 7.4 at 37 degreesC. The release data show that the release of IMM is faster than for EtBr. During the first stage, the release of IMM is governed by osmotic pressure whereas the release of EtBr is mainly diffusion controlled. The in vitro release of these drugs is governed by polymer matrix degradation at the later stage of the release process. The in vitro release could be controlled by drug loading, polymer molecular mass, polymer mixtures, coating thickness and device geometry.

Biocompatible Materials↗
PubMed1998

In vitro dissociation of antifungal efficacy and toxicity for amphotericin B-loaded poly(ethylene oxide)-block-poly(beta benzyl L aspartate) micelles.

Amphotericin B (AmB) is a membrane-active drug used frequently for the treatment of systemic fungal diseases. Limitations for the use of AmB include poor water solubility and potential for serious systemic toxicities. Recently, it has been demonstrated that the aggregation state of AmB is a determinant factor for toxicity. To increase its therapeutic index, AmB has been solubilized in micelles based on poly(ethylene oxide)-block-poly(beta-benzyl-l-aspartate) (PEO-block-PBLA), using a dialysis method of drug loading. The aggregation state of AmB has been investigated by electronic absorption spectroscopy. AmB loaded in PEO-block-PBLA micelles is non-hemolytic for concentrations up to 15 microgram/ml. AmB as Fungizone(R) initiates hemolysis at 1.0 microgram/ml. The onset of hemolysis correlates with the respective critical aggregation concentrations (CACs) of AmB. The antifungal activity of the AmB-loaded PEO-block-PBLA micelles is four to eight times higher than Fungizone(R) in terms of minimal inhibitory concentrations (MICs). PEO-block-PBLA has no antifungal activity for concentrations up to 200 microgram/ml. The basis for the increase in antifungal activity of AmB-loaded PEO-block-PBLA micelles is unclear, but may be related to a stabilizing effect of the polymeric micelles against auto-oxidation of the AmB heptaene moiety or alternatively, an enhancement in membrane perturbation of fungal cells.

Amphotericin B↗
PubMed1999

Modulated release of IdUrd from poly (D,L-lactide-co-glycolide) microspheres by addition of poly (D,L-lactide) oligomers.

This paper reports the release characteristics of a radiosensitizer, 5-iodo-2'-deoxyuridine (IdUrd), from poly (D,L-lactide-co-glycolide) 50: 50 (PLGA) microparticles obtained by a phase separation technique. Poly (D,L-lactide) oligomers (D,L-PLA) were incorporated into the PLGA matrix in order to accelerate the overall drug release rate and regulate the triphasic release profile exhibited by the standard PLGA microparticles. For D,L-PLA (800), the burst effect was large and the IdUrd release was complete between 28 and 35 days. These results were attributed to rapid pore formation on the periphery of the microsphere in the early stages of incubation, due to hydrosolubility of the smallest oligomers (D,L-PLA (800)). In the case of D,L-PLA (1,100), drug release occurred over a six week period, the standard time course of conventional radiation therapy. The period during which the radiosensitizer was incorporated in human brain tumor cell nuclei after its entrapment in biodegradable microspheres was determined by using an organotypical tissue culture. The presence of radiosensitizer in the DNA of tumor cell nuclei was detected by immunohistochemical labelling of tumor fragments. IdUrd release from standard microspheres (7+/-0.5 weeks) was longer than from oligomer-containing batches. For D,L-PLA (800)-containing microspheres, the radiosensitizer was entirely released within 4. 5+/-0.5 weeks. The microspheres containing D,L-PLA (1,100) allowed an IdUrd release over a 5 to 6 week period. The ex vivo data were consistent with the in vitro findings in terms of release duration.

Biodegradation, Environmental↗