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At least 955 records · Page 53Linked to original sources
PubMed2002

Poly(lactic acid) microspheres for the sustained release of antiischemic agents.

We report a preliminary study evaluating the encapsulation modalities in microparticles of the antiischemic drug N(6)-cyclopentyladenosine (CPA). The effects of release systems have been evaluated on the stability in human whole blood of CPA and its affinity toward human adenosine A(1) receptors. The microspheres were prepared by an emulsion-solvent evaporation method (different CPA amounts and two stirring rates were employed) using poly(lactic acid). Free and encapsulated CPA was incubated in human blood and the drug stability was analyzed. The affinity of CPA to human A(1) receptor was also obtained in the presence and in the absence of unloaded microspheres. The microspheres obtained using 1200 rpm showed a broad size distribution and a mean diameter value of 21+/-9 microm. Using 1700 rpm the mean diameter decreased to 5+/-2 microm and a more homogeneous size distribution was obtained. The CPA release changed with the particle size and the different amounts of drug employed during the preparation of the microspheres. The degradation in human whole blood of CPA encapsulated in the microspheres was negligible, with respect to that of free CPA. Affinity values of CPA obtained in the absence and in the presence of unloaded microspheres were the same.

Adenosine↗
PubMed2003

PLGA microspheres for oral osteopenia treatment: preliminary "in vitro"/"in vivo" evaluation.

The aim of this work was to prepare and to evaluate "in vitro"/"in vivo" microspheres based on poly(D,L-lactide-co-glycolide) copolymers containing ipriflavone, for the local treatment of oral bone loss. The first objective was the preparation and "in vitro" characterization of ipriflavone loaded microspheres, by emulsion/solvent evaporation method. Process parameters such as drug:polymer weight ratio, and molecular weight of copolymers, were also investigated. The second objective was to elaborate a suitable animal model of mandibular osteoporosis, to evaluate the efficacy of these microparticulate drug delivery systems. "In vivo" experiments were carried out on female rats, in which oral osteopenia was induced by gonadectomy and molar avulsion. Morphometric analysis of mandibular segment were carried out to quantify the development of oral osteopenia and the efficacy of drug loaded microspheres. Results showed that ipriflavone loaded PLGA microspheres can be successfully obtained with good "in vitro" characteristics, utilizing the emulsification/solvent evaporation method. "In vivo" experiments revealed that local administration of microspheres produced only mild inflammation on the injection site. Morphometric analyses showed, at the level of the third molar, a slight increase in spongy and total bone mass on rat jaw treated with microspheres with respect to control. Control animals exhibited a scarce degree of osteopenia demonstrating that this animal model is not suitable for this purpose.

Animals↗
PubMed1999

Investigation on process parameters involved in preparation of poly-DL-lactide-poly(ethylene glycol) microspheres containing Leptospira Interrogans antigens.

Block copolymer, poly-DL-lactide-poly(ethylene glycol) (PELA) with 11.5% of poly(ethylene glycol) (PEG) content was prepared by bulk ring-opening polymerization using stannous chloride as initiator. PELA microspheres with entrapped Leptospira Interrogans antigens, outer membrane protein (OMP) were elaborated by solvent extraction method based on the formation of multiple w/o/w emulsion, and the resulting microspheres were characterized with respect to particle size, OMP entrapment and morphology characteristics. The purpose of the present study is to perform the optimization of preparative parameters for OMP-loaded PELA micropsheres to control particle size and improve the OMP encapsulation efficiency. Of all the parameters investigated, the polymer concentration of organic phase and the external aqueous phase volume play major roles on particle size, while the organic phase volume, internal aqueous phase volume and the addition of surfactant into the internal aqueous phase display considerable effects on OMP loading efficiency. A small volume of internal aqueous phase and intermediate volumes of organic phase and external aqueous phase were favorable to achieve micropsheres with a size of 1-2 microns and high antigen encapsulation efficiency (70-80%). In vitro OMP release profiles from PELA microspheres consist of a small burst release followed by a gradual release phase. The OMP release rate shows some relations with the porous and water-swollen inner structure of the microspheres matrix. The presence of surfactant in microspheres accelerates OMP release, but the OMP entrapment within microspheres shows limited effects on the release profile.

Antigens, Bacterial↗
PubMed1999

The transport of polymeric microspheres across the ciliated epithelia of the bullfrog.

The influence of some hydrophilic polymers on the clearance of particles across the ciliated epithelium of the bullfrog palate has been examined. The polymers studied were Carbopol 907 cross-linked with maltose to provide microspheres of varying cross-link density, Carbopol 934P, hydroxypropylmethylcellulose, chitosan and poly(vinyl alcohol). Transport rates were determined relative to glass spheres. The polymers in dilute solution (0.1 and 0.5% w/v) resulted in a reduction in the transport rate of the glass spheres. For non-cross-linked microspheres, Carbopol 934P exhibited a lower transport rate than the more slowly hydrating chitosan. The cross-linked poly(acrylic acid) microspheres showed clearance rates which were dependent on the cross-link density. Incorporation of some preservatives (EDTA, methylhydroxybenzoate, chlorbutol and chlorocresol), known to reversibly retard clearance, into the cross-linked poly(acrylic acid) microspheres produced effects dependent on cross-link density: lightly cross-linked microspheres were cleared more slowly than the preservative-free microspheres whilst for more heavily cross-linked particles the converse was observed.

Animals↗
PubMed2001

Effects of anterior inferior cerebellar artery occlusion on cochlear blood flow--a comparison between laser-Doppler and microsphere methods.

The effects of anterior inferior cerebellar artery (AICA) occlusion on blood flow were investigated in rats using the laser-Doppler and microsphere methods. A specially designed microclamp was held in a micromanipulator and positioned to occlude the left AICA. After the middle ear mucosa had been removed, a 1.0-mm laser-Doppler probe was placed on the basal turn of the left cochlea. Non-radioactive microspheres were injected intracardially during the AICA occlusion and the numbers of microspheres in various parts of the cochlea were counted, including in the bone surrounding the cochlea. Upon AICA clamping, the blood flow measured by laser-Doppler flowmetry decreased to 46.9+/-11.9% of the baseline value, and the number of microspheres trapped in the cochlea was 17.2+/-13.3% compared with the contralateral side in 15 animals. The number of microspheres in the bone surrounding the cochlea in the AICA-clamped side was 81+/-15% of that of the contralateral side. In animals in which there were few if any microspheres in the cochlea, laser-Doppler output was 30-40% of the baseline value. From these findings, we infer that during complete interruption of cochlear blood flow in rats, residual laser-Doppler output was essentially attributable to blood flow in the bone surrounding the cochlea.

Animals↗
PubMed2002

Preliminary report on the biocompatibility of a moldable, resorbable, composite bone graft consisting of calcium phosphate cement and poly(lactide-co-glycolide) microspheres.

We have assessed the biocompatibility of a new composite bone graft consisting of calcium phosphate cement (CPC) and poly(lactide-co-glycolide) (PLGA) microspheres (approximate diameter of 0.18-0.36 mm) using cell culture techniques. CPC powder is mixed with PLGA microspheres and water to yield a workable paste that could be sculpted to fit the contours of a wound. The cement then hardens into a matrix of hydroxyapatite microcrystals containing PLGA microspheres. The rationale for this design is that the microspheres will initially stabilize the graft but can then degrade to leave behind macropores for colonization by osteoblasts. The CPC matrix could then be resorbed and replaced with new bone. In the present study, osteoblast-like cells (MC3T3-E1 cells) were seeded onto graft specimens and evaluated with fluorescence microscopy, environmental scanning electron microscopy and the Wst-1 assay (an enzymatic assay for mitochondrial dehydrogenase activity). Cells were able to adhere, attain a normal morphology, proliferate and remain viable when cultured on the new composite graft (CPC-PLGA) or on a control graft (CPC alone). These results suggest that our new cement consisting of CPC and PLGA microspheres is biocompatible. This is the first time that a 'polymer-in-mineral' (PLGA microspheres dispersed in a CPC matrix) cement has been formulated that is moldable, resorbable and that can form macropores after the cement has set.

Animals↗
PubMed1999

Pectin microspheres as ophthalmic carriers for piroxicam: evaluation in vitro and in vivo in albino rabbits.

Microparticulate polymeric delivery systems have been suggested as a possible approach to improve the low bioavailability characteristics shown by standard ophthalmic vehicles (collyria). Purpose of this study was the evaluation of pectin microspheres as delivery system for piroxicam (Px). The microspheres were prepared by a spray-drying technique; their morphological characteristics were investigated by scanning electron microscopy (SEM), and their in vitro release behavior was evaluated in pH 7.0 USP buffer using a flow-through apparatus. Px loaded in the pectin microspheres showed a faster in vitro dissolution rate with respect to solid micronized drug. The precorneal retention of fluorescein-loaded microspheres was evaluated in vivo in albino rabbits: an aqueous dispersion of fluorescent microspheres showed a significantly increased residence time in the eye (2.5 vs. 0.5 h) when compared with a fluorescein solution. In vivo tests in rabbits of dispersions of Px-loaded microspheres also indicated a significant improvement of Px bioavailability in the aqueous humour (2.5-fold) when compared with commercial Px eyedrops. The potential advantages and limitations of this delivery system are discussed.

Animals↗
PubMed2000

Radiolabelled biodegradable microspheres for lung imaging.

The effect on lung accumulation of modifying the surface compositions of (99m)Tc poly(lactide-co-glycolide) (PLGA) and (99m)Tc poly(ethylene glycol)-poly(lactide-co-glycolide) (PEG-PLGA) microspheres with different surfactants was assessed after intravenous injection into rats. Microspheres were prepared with PLGA or PEG-PLGA by the emulsion solvent evaporation method using polyvinyl alcohol (PVA), polyethylene glycol (PEG), albumin (BSA) or poloxamer 188 as surfactant, in the external aqueous phase. Commercial human albumin microspheres (Sferotec((R)), HAM) were used as reference. According to the European Pharmacopeia, >80% of (99m)Tc-HAM in the size range 10-50 microm, must be accumulated in the lung 15 min after intravenous administration. By modifying the surfactant, the resulting lung accumulation was 99% for (99m)Tc-HAM, and more than 50% for PLGA microspheres prepared with poloxamer 188 (1 and 4%), reaching 67% with 8% Poloxamer 188 and around 30-39% for PLGA and PEG-PLGA microspheres prepared with the other surfactants. PLGA microspheres made with 8% poloxamer 188 gave good quality lung images under a gamma camera for the first few minutes, subsequently liver radioactivity masked lung images.

Animals↗
PubMed2002

Anti-cancer drug diffusion within living rat brain tissue: an experimental study using [3H](6)-5-fluorouracil-loaded PLGA microspheres.

This study was performed (i) to monitor the diffusion of the anti-cancer drug 5-fluorouracil (5-FU) and (ii) to elucidate the fate of poly(lactide-co-glycolide) (PLGA) based microspheres within living rat brain tissue upon intracranial implantation. Drug-loaded microparticles were prepared using a solvent emulsion/extraction process and administered into healthy and C6 glioma-bearing Sprague-Dawley rats. The same surgical procedure was carried out with magnetite-loaded microspheres. To monitor 5-FU diffusion from the implantation site, tissue combustion was performed on animals implanted with tritiated drug microspheres. T2-weighted nuclear magnetic resonance imaging was undertaken on animals implanted with magnetite-loaded microspheres to determine microsphere localization after deposit. Results show that an important microparticle backflow occurs in healthy rats, whereas the microspheres remain at the site of administration in C6 glioma-bearing rats. Drug diffusion is limited to the vicinity of the implantation site.

Animals↗
PubMed1998

Protein encapsulation and release from poly(lactide-co-glycolide) microspheres: effect of the protein and polymer properties and of the co-encapsulation of surfactants.

Despite the recognised role of the poly(lactide-co-glycolide) (PLGA) in the encapsulation and release of proteins from PLGA microspheres, the importance that the characteristics of the protein have in these processes has not yet been sufficiently investigated. The aim of this work was to study the simultaneous effect of the protein and PLGA properties and of the microencapsulation process on the physicochemical and in vitro release characteristics of protein-loaded PLGA microspheres. Two model proteins of different isoelectric points (pI), bovine serum albumin (BSA) (pI = 4.6) and lysozyme (LZM) (pI = 11.2), and two different molecular weights (Mw) of PLGA were selected. Microspheres were prepared using the water-in-oil-in-water (w/o/w) solvent extraction and the oil-in-oil (o/o) solvent evaporation techniques. Results showed that BSA was efficiently encapsulated independent of the PLGA Mw, whereas the encapsulation of LZM was favoured with the low Mw PLGA. The co-encapsulation of a surfactant (poloxamer 188 or 331) reduced the protein encapsulation efficiency, especially of BSA. These results suggested that the tensoactive properties of the protein and its affinity for the PLGA are major determinants of the protein encapsulation. Both proteins released faster from the microspheres prepared by the o/o solvent evaporation procedure, with respect to those prepared by the w/o/w solvent extraction technique. In addition, both polymer Mw and protein type had an effect on the protein release rate. The release rate of both proteins, in the absence of a surfactant, was faster from the low Mw PLGA microspheres. However, the release rate constant was higher for BSA than for LZM irrespective of the PLGA Mw. In addition, the co-encapsulation of a surfactant led, in most cases, to a faster release of the encapsulated protein. To conclude, these results suggest that protein release from PLGA microspheres is not only governed by the PLGA erosion rate and protein diffusion through the water-filled channels, but is highly affected by the protein properties and its possible interaction with PLGA and its degradation products.

Chemical Phenomena↗
PubMed2000

In vitro and in vivo characterization of biodegradable enoxacin microspheres.

The in vitro release and plasma concentration profiles of sustained release enoxacin microspheres intended for the treatment of bone and systemic infections due to sensitive strains of bacteria were investigated. Microspheres of enoxacin were prepared by using poly(glycolic acid-co-DL-lactic acid) (PLGA) by the emulsion solvent evaporation technique and characterized by in vitro release in an incubator, and in vivo release in the rat subcutaneous model. The microspheres were spherical in nature, and particle size range had a significant influence on the in vitro release. The enoxacin plasma concentration 2 h after the administration of treatments was two-fold higher in animals who received the free drug compared with those who received microspheres of size range 125-250 microm. The plasma of animals who received the free drug was depleted of enoxacin by the end of the first day. However, the plasma concentration of enoxacin in the animals who received microspheres was sustained above 0.5 microg/ml for about 8 days. The results show that biodegradable microspheres of enoxacin can be prepared which release the antibiotic in vivo for days following a subcutaneous administration. This should provide a means for the sustained treatment of infections due to sensitive strains of bacteria.

Animals↗
PubMed2000

Pore sizes in hydrated dextran microspheres.

The average pore size of hydrated dextran microspheres is derived from rheological and protein release data. The microspheres were prepared by cross-linking an aqueous solution of methacrylated dextran emulsified in a continuous poly(ethylene glycol) phase. The rheological data were obtained using a novel micromanipulation technique, which enables the compression of a single microsphere. The so obtained pseudoelasticity moduli of the microspheres were derived from these compression data and corresponded well with the elasticity moduli of macroscopic hydrogels of the same composition, as determined with dynamic mechanical analysis. The modulus increased with decreasing water contents of the microspheres and with increasing degrees of methacrylate substitution of the dextran used. Furthermore, the average pore sizes calculated from the pseudoelasticity moduli were in good agreement with the pore sizes derived from protein release data. In conclusion, this study shows that micromanipulation provides insight into the average pore sizes of dextran microspheres, which is an important characteristic that will modulate the release of encapsulated proteins.

Dextrans↗
PubMedDate not supplied

Production of microspheres with surface amino groups from blends of Poly(Lactide-co-glycolide) and Poly(epsilon-CBZ-L-lysine) and use for encapsulation.

Microspheres were formed from blends of the biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) together with poly(epsilon-CBZ-L-lysine) (PCBZL) by a double-emulsification/solvent evaporation technique. The size of the microspheres formed by this method was dependent both on the total concentration of the polymers and on the ratio of PLGA to PCBZL. The use of the microspheres for encapsulation was demonstrated by the inclusion of a solution of Texas Red fluorescent dye. Lysine epsilon-amino groups on the surface of the microspheres were deprotected by acid hydrolysis or lithium/liquid ammonia reduction. Acid hydrolysis damaged the surface of the microspheres as assessed by scanning electron microscopy, whereas deprotection by lithium/ammonia produced less damage and allowed the retention of encapsulated dye solution. The surface lysine groups made available on the surface of the microspheres could be used to covalently link a variety of biologically active molecules to alter their in vivo properties and allow targeting to specific cell types.

Biocompatible Materials↗
PubMed2006

Formation and characterization of polyglutamate core-shell microspheres.

The need for organ-targeted delivery of drugs and imaging agents creates an interest in biocompatible, biodegradable vesicles. We make protein microspheres using high-intensity ultrasound; these microspheres have a protein shell and a hydrophobic interior, making them ideal for delivering hydrophobic materials. We have previously shown that various proteins, e.g., bovine serum albumin (BSA), form a microsphere shell stabilized by interprotein cross-linking of cysteine residues. In this study, polyglutamate was used to form core-shell microspheres at slightly basic pH using sonication. These particles are smaller than our previous protein microspheres and are stable under conditions encountered in vivo. The stability of polyglutamate microspheres appears to be due to hydrogen bonding networks and not covalent cross-linking.

Biocompatible Materials↗
PubMed1996

Optimization of the formulation design of chitosan microspheres containing cisplatin.

This study describes an orthogonal experimental design to optimize the formulation of cisplatin (CDDP)-loaded chitosan microspheres (namely, CDDP-DAC-MS) which were produced by an emulsion-chemical cross-linking technique. Seven factors and three levels for each factor that might affect the formulation of microspheres were selected and arranged in an L27(3(13)) orthogonal experimental table. A desirability function (df) calculated according to the trapping efficiency of CDDP, the drug content (%, w/w), and the size distribution of each batch of microspheres was introduced as an index of the microsphere formulation. The overall desirability functions (DF) were produced and treated by a statistic analytical system to optimize the formulation. Moreover, the contour maps were produced to analyze the influence of the seven factors on the size distribution, the drug content, and the drug trapping efficiency. The established optimum procedure was reproducible. Scanning electron micrographs showed that CDDP-DAC-MS were spherical with a coarse surface. The average diameter, drug content, and drug trapping efficiency of CDDP-DAC-MS were 74.8 microns, 20.8% (w/w), and 77.5%, respectively. The in vitro release of cisplatin from chitosan microspheres in saline was retarded compared with that from saline solution; the release of CDDP from chitosan microspheres was suggested to be controlled by the dissolution and diffusion of the drug from the chitosan matrix.

Chitin↗
PubMed2005

Selective, controllable, and reversible aggregation of polystyrene latex microspheres via DNA hybridization.

The directed three-dimensional self-assembly of microstructures and nanostructures through the selective hybridization of DNA is the focus of great interest toward the fabrication of new materials. Single-stranded DNA is covalently attached to polystyrene latex microspheres. Single-stranded DNA can function as a sequence-selective Velcro by only bonding to another strand of DNA that has a complementary sequence. The attachment of the DNA increases the charge stabilization of the microspheres and allows controllable aggregation of microspheres by hybridization of complementary DNA sequences. In a mixture of microspheres derivatized with different sequences of DNA, microspheres with complementary DNA form aggregates, while microspheres with noncomplementary sequences remain suspended. The process is reversible by heating, with a characteristic "aggregate dissociation temperature" that is predictably dependent on salt concentration, and the evolution of aggregate dissociation with temperature is observed with optical microscopy.

Base Sequence↗
PubMed2000

Injectable chemotherapeutic microspheres and glioma I: enhanced survival following implantation into the cavity wall of debulked tumors.

PURPOSE: Implantation of biodegradable polymers provides a powerful method to deliver high, sustained concentrations of chemotherapeutics to brain tumors. The present studies examined the ability of injectable polymeric microspheres, formulated to release carboplatin or BCNU for 2-3 weeks, to enhance survival in a rodent model of surgically-resected glioma. METHODS: Rat glioma (RG2) cells were implanted into the cortex of rats and allowed to grow for 10 days prior to surgical resection. Rats were given either surgical resection only, bolus injection (100 microg) or microspheres containing 10, 50, or 100 microg of carboplatin or BCNU. The microspheres were implanted, via hypodermic injection, either directly into the surgical cavity or into the tissue along the perimeter of the cavity. RESULTS: The order of survival among treatment groups was: no resection < resection only < bolus chemotherapy < sustained release chemotherapy. Carboplatin and BCNU did not differ in this respect and in each case, the enhanced survival achieved with sustained release was dose-related. However, the enhanced survival achieved with carboplatin was substantially greater when the microspheres were implanted into the perimeter wall of the resection cavity, compared to implantation into the cavity itself. The enhanced survival produced by carboplatin implants along the resection perimeter was associated with a significant attenuation of regrowth of the tumor. Finally, in a separate study in non-tumor brain, atomic absorption spectrophotometry revealed that while the microspheres produced significantly prolonged tissue levels of carboplatin relative to a bolus injection, carboplatin diffusion was limited to brain tissue extending primarily 0.5 mm from the injection site. CONCLUSIONS: These data demonstrate: (1) that sustained delivery of chemotherapy is superior to equipotent bolus doses following tumor resection, and (2) that direct injection of sustained release microspheres into the tissue surrounding a growing tumor mass may provide superior effects over injections into the surgical cavity. They also suggest that successful implementation of this approach in humans may require measures or circumstances that improve upon the limited spatial drug diffusion from the implantation site.

Animals↗
PubMed1997

Stereoselective disposition of suspensions of conventional and wax-matrix sustained release ibuprofen microspheres in rats.

PURPOSE: The aim of the study is to evaluate stereoselective in vivo disposition of suspensions of conventional and wax-matrix sustained release ibuprofen microspheres in rats. METHODS: Male wistar rats were dosed i.v. with 20 mg/kg, or orally with conventional suspension, and three suspension formulations of sustained release microspheres (having three different particle sizes) of racemic ibuprofen. Blood samples were analyzed stereoselectively by reverse phase HPLC. RESULTS: The mean Cmax for (S)- and (R)-ibuprofen decreased with increased particle size of the drug or microspheres in the suspension dosage forms, while the Tmax increased with increased particle size. The mean S/R ratio (AUC0-48) of the suspensions decreased with increase in particle size of the drug or microspheres and these ratios (for both conventional and sustained formulations) were higher than that of the i.v., an indication of presystemic inversion. Decrease in the ratios with increased particle size is suggestive of formulation dependent inversion. The plasma concentration-time data of the sustained release formulations showed bimodal profiles, irrespective of the particle size of the microspheres. The second peak observed after 8 hours is indicative of colonic absorption. CONCLUSIONS: Stereoselective disposition of ibuprofen microspheres showed higher bioavailability compared to the conventional suspension. Bimodal disposition is influenced by dosage form while presystemic inversion is both site-specific, and dosage form dependent.

Administration, Oral↗