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 163 records · Page 9Linked to original sources
PubMed2005

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres.

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by UV/VIS spectrophotometry. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15 000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15 000, 20 000 and 30 000 were 62.75, 27.52 and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30 000 microspheres to 3.97% of PLGA 15 000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increase in oil phase and PVA concentration decreased in aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.

Alkaloids↗
PubMed2005

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: characterization and drug release.

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47 +/- 11 and 67 +/- 12 microg 5-FU mg(-1) microspheres and the percentage of entrapment efficiency was between 52 +/- 12 and 74 +/- 13. Microspheres were of small size (average diameter: 0.9 +/- 0.4-1.4 +/- 0.8 microm microspheres without drug; 1.1 +/- 0.5-1.7 +/- 0.9 microm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger Tg. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of Tg of the polymer of the microspheres. The presence of 5-FU did not modify the Tg values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28-129 h) was in the order PLA > PLGA 75/25 > PLGA 50/50. A burst effect (17-20%) was observed during the first hour and then a period of constant release rate (3.52 +/- 0.82-1.46 +/- 0.26 microg 5-FU h(-1) per milligram of microspheres) up to 8 or 13 h, depending on the polymer, was obtained.

Antimetabolites, Antineoplastic↗
PubMed2005

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres.

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15,000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15,000, 20,000 and 30,000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30,000 microspheres to 3.97% of PLGA 15,000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.

Alkaloids↗
PubMed2006

Characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres as affected by chitosan molecular weight.

In this paper, the effect of chitosan molecular weight on the characteristics (size, encapsulation efficiency, zeta potential, surface morphology and release rate) of vitamin C encapsulated tripolyphosphate cross-linked chitosan (TPP-chitosan) microspheres. The molecular weight of chitosan had a noticeable influence on the size, encapsulation efficiency, zeta potential, surface morphology and controlled release behaviour of the vitamin C encapsulated TPP-chitosan microspheres. The mean particle size and encapsulation efficiencies of TPP-chitosan microspheres were 3.1, 4.9 and 6.7 microm and 67.25, 60.43 and 52.74% for the microspheres prepared using low, medium and high molecular weight chitosan, respectively. All the TPP-chitosan microspheres (low, medium and high molecular weight) had positive charge on their surface. The zeta potential of the TPP-chitosan microspheres prepared using low, medium and high molecular weight chitosan was 41.25, 40.84 and 39.13 mV, respectively. The particle sizes of TPP-chitosan microspheres increased with increases in chitosan molecular weight. Molecular weight of chitosan did not affect significantly the % yield of TPP-chitosan microspheres prepared by spray-drying. The influence of chitosan molecular weight on the surface morphology of vitamin C encapsulated TPP-chitosan microspheres was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was observed that, as the molecular weight of chitosan increases, TPP-chitosan microspheres with uniform spherical shape could be obtained. The physical state of vitamin C (amorphous or crystalline) in TPP-chitosan matrix was studied by X-ray diffraction (XRD) and it was found that vitamin C is dispersed at the molecular level (amorphous) in the TPP-chitosan matrix. Release rate of the vitamin C from TPP-chitosan microspheres was significantly affected by the chitosan molecular weight. The release rate decreased with increase in the chitosan molecular weight. The release of vitamin C from TPP-chitosan microspheres followed Fick's law of diffusion.

Ascorbic Acid↗
PubMed2006

Formulation and in vitro evaluation of bisphosphonate loaded microspheres for implantation in osteolysis.

Chitosan and poly(lactide-co-glycolide) acid (PLGA) microspheres loaded with alendronate sodium (AS) were prepared for orthopedic as well as dental applications. In orthopedics the aim was to make the total joint prostheses stay in the body for a long time without causing bone tissue loss, while in dentistry it was aimed to treat the alveolar bone resorption caused by periodontitis and also to make the dental treatment using implants easier by reducing the bone loss in patients with osteoporosis. Solvent evaporation method was used to prepare AS loaded PLGA microspheres and emulsion polimerization method was used to prepare AS loaded chitosan microspheres. Particle size, loading efficacy, surface characteristics, and in vitro release characteristics were examined on prepared formulations. After the examination of the scanning electron microscopy photographs of microspheres, chitosan microspheres were observed to have spherical structure and smooth surface characteristics while PLGA microspheres were observed to have spherical porous surface structure. Loading efficacy was found to be 3.30% for chitosan microspheres and 7.70% for PLGA microspheres. It was observed that 85% of AS had been released at the end of the third day from chitosan microspheres whereas 58% was released at the end of the fifth day from PLGA microspheres. It was found that chitosan microspheres gave first order release while PLGA microspheres gave zero order release.

Alendronate↗
PubMedDate not supplied

Comparison of in vitro and in vivo release characteristics of sustained release ofloxacin microspheres.

The sustained release nature of ofloxacin microspheres--to eradicate bacterial biofilm associated with chronic infections from sensitive strains of bacteria--was determined both in vitro and in vivo. Ofloxacin microspheres were prepared by emulsion solvent evaporation procedure using poly(glycolic acid-co-dl-lactic acid) (PLGA) as the biodegradable polymer. The microspheres were characterized by scanning electron microscopy, in vitro release in an incubator, and in vivo release in the rat subcutaneous model. The microspheres were highly spherical with a very smooth surface. Approximately 45% of the drug was released from microspheres in sizes of 125-250 microns and 250-425 microns in 2 days compared with approximately 22% from microspheres of size range 37-125 microns indicating that surface area of the microspheres did not control the kinetics of in vitro release. However, about 96% of the drug was released from the three different size ranges in 35 days. The in vitro release profile of microspheres of size range 125-250 microns is not significantly different from microspheres in sizes of 250-425 microns. The peak plasma level of ofloxacin in animals that received the drug suspension occurred within 2 hr and was higher than that of the microspheres that occurred by the end of the second day. The plasma of animals that received the free drug was depleted of ofloxacin by the end of the first day, but the drug was sustained above 0.5 microgram/mL in the plasma of animals that received the microspheres for about 3 weeks. The results suggest that biodegradable ofloxacin microspheres can be prepared that release the antibiotic in vivo for about 3 weeks. This should provide a means for continuous treatment of chronic infections in which bacterial biofilm can occur.

Animals↗
PubMedDate not supplied

Poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for cartilage tissue engineering.

Injectable scaffold has raised great interest for tissue regeneration in vivo, because it allows easy filling of irregularly shaped defects and the implantation of cells through minimally invasive surgical procedures. In this study, we evaluated poly(lactic-co-glycolic acid) (PLGA) microsphere as an injectable scaffold for in vivo cartilage tissue engineering. PLGA microspheres (30-80 microm in diameter) were injectable through various gauges of needles, as the microspheres did not obstruct the needles and microsphere size exclusion was not observed at injection. The culture of chondrocytes on PLGA microspheres in vitro showed that the microspheres were permissive for chondrocyte adhesion to the microsphere surface. Rabbit chondrocytes were mixed with PLGA microspheres and injected immediately into athymic mouse subcutaneous sites. Chondrocyte transplantation without PLGA microspheres and PLGA microsphere implantation without chondrocytes served as controls. Four and 9 weeks after implantation, chondrocytes implanted with PLGA microspheres formed solid, white cartilaginous tissues, whereas no gross evidence of cartilage tissue formation was noted in the control groups. Histological analysis of the implants by hematoxylin and eosin staining showed mature and well-formed cartilage. Alcian blue/safranin O staining and Masson's trichrome staining indicated the presence of highly sulfated glycosaminoglycans and collagen, respectively, both of which are the major extracellular matrices of cartilage. Immunohistochemical analysis showed that the collagen was mainly type II, the major collagen type in cartilage. This study demonstrates the feasibility of using PLGA microspheres as an injectable scaffold for in vivo cartilage tissue engineering. This scaffold may be useful to regenerate cartilaginous tissues through minimally invasive surgical procedures in orthopedic, maxillofacial, and urologic applications.

Animals↗
PubMed1996

Glucocorticoids prolong rat sciatic nerve blockade in vivo from bupivacaine microspheres.

BACKGROUND: Previous work showed that incorporation of dexamethasone (0.05 weight/weight percentage) into bupivacaine microspheres prolonged blockade by eight to 13 times compared with that produced by bupivacaine microspheres alone. The determinants of dexamethasone's block-prolonging effect were examined and reported here. METHODS: Polylactic-co-glycolic acid polymer microspheres (65/35) with 75 weight/weight percentage bupivacaine were prepared. Microspheres were injected adjacent to the rat sciatic nerve, and sensory and motor blockade were assessed. A procedure was developed to test drugs for block-prolonging ability in vivo by placing test drugs in the injection fluid along with a suspension of bupivacaine microspheres. RESULTS: Dexamethasone alone in suspension did not produce blockade, nor did it prolong blockade induced by aqueous bupivacaine. Bupivacaine microspheres (150 mg drug/kg rat weight) produced blockade for 6 to 10 h. Dexamethasone in the suspending solution of microspheres prolonged block by up to five times. Glucocorticoids prolonged block in proportion to glucocorticoid/antiinflammatory potency. The corticosteroid antagonist cortexolone inhibited dexamethasone's blockade-prolonging action. Durations of blockade with or without dexamethasone were unaltered by hydroxyurea-induced neutrophil depletion. Microspheres were extracted from rats at time points ranging from 7 h to 7 days, and residual microsphere dry weight and bupivacaine content were similar in groups of rats injected with either bupivacaine microspheres or bupivacaine microspheres containing dexamethasone, respectively. CONCLUSIONS: Glucocorticoids prolong blockade from bupivacaine microspheres. The mechanism appears unrelated to the kinetics of bupivacaine release in vivo.

Anesthetics, Local↗
PubMed2004

Migration studies and histology of injectable microspheres of different sizes in mice.

Injectable dermal filler materials consist of either fluids, biological fragments, or suspensions of particles or microspheres. Particles and microspheres are said to "migrate," but migration can occur only when they are injected into blood vessels. To evaluate biocompatibility and transport, five nonresorbable polymethylmethacrylate microspheres of various sizes, suspended in different carriers, as well as resorbable polylactic acid and dextran microspheres were injected subcutaneously into mice. The five implantation sites were the right cheek, right axilla, right groin, urethra, and the right quadriceps muscle of the thigh. These sites were excised along with the local lymph nodes, lungs, liver, and spleen at 1, 3, 6, and 9 months after injection. Polymethylmethacrylate microspheres of 4 microm and 8 microm were phagocytosed but not transported to lymph nodes or distant organs. Larger microspheres of 20, 40, and 100 microm were encapsulated by connective tissue, macrophages, and giant cells. Polylactic acid microspheres caused a mild inflammatory response and had disappeared at 6 months. Dextran microspheres caused a pronounced foreign-body reaction and were phagocytosed at 9 months. The extremely large carbon-coated spheres of 200 to 500 microm in diameter "migrated" up to 1 cm from the implantation site. With the exception of an erroneous intravenous injection, no migration or transportation of any of the injected microspheres to lymph nodes or filter organs was seen. Obviously, the collagen glue released no microspheres. After subdermal injection, the collagen carrier substance kept the microspheres apart as a scaffold for tissue ingrowth, whereas all other carrier substances, such as gelatin, hyaluronic acid, or alginate, separated soon after injection, thereby causing agglomeration of the microspheres.

Animals↗
PubMed1998

Evaluation of oral mucoadhesive microspheres in man on the basis of the pharmacokinetics of furosemide and riboflavin, compounds with limited gastrointestinal absorption sites.

When sustained-release adhesive and non-adhesive microspheres which release the same drugs at similar rates are administered orally, drug absorption after administration of adhesive microspheres should, if the gastrointestinal residence of adhesive microspheres is prolonged as a result of mucoadhesion, be higher than that after administration of non-adhesive microspheres. The gastrointestinal transit of oral adhesive microspheres in man has been evaluated pharmacokinetically using furosemide and riboflavin, compounds with limited absorption sites in the upper small intestine. In a preliminary experiment with fasted rats it was confirmed that a higher percentage of the drug remained in the stomach and that plasma drug levels were higher when furosemide was administered in the form of adhesive rather than non-adhesive microspheres. Two kinds of sustained-release microsphere, adhesive and non-adhesive, containing furosemide and riboflavin in hard gelatin capsules were prepared and orally administered to 10 healthy fasted volunteers in a cross-over design. Areas under the plasma concentration-time curves (AUC) were 1.8 times larger for furosemide and urinary recovery was 2.4 times higher for riboflavin when adhesive microspheres rather than when non-adhesive microspheres were used. When adhesive microspheres containing riboflavin were administered to fed volunteers, urinary recovery was 2.1 times higher and mean residence time (MRT) was more prolonged than when the microspheres were administered to fasted volunteers. Adhesive microspheres were found to adhere to the gastric or intestinal mucosa with high affinity in man and rats, resulting in prolonged gastrointestinal residence.

Adhesives↗
PubMed2000

Hemodynamic effects of 15-microm-diameter microspheres on the rat pulmonary circulation.

The microsphere method has been used extensively to measure regional blood flow in large laboratory animals. A fundamental premise of the method is that microspheres do not alter regional flow or vascular tone. Whereas this assumption is accepted in large animals, it may not be valid in the pulmonary circulation of smaller animals. Three studies were performed to determine the hemodynamic effects of microspheres on the rat pulmonary circulation. Increasing numbers of 15-microm-diameter microspheres were injected into a fully dilated, isolated-lung preparation. Vascular resistance increased 0.8% for every 100,000 microspheres injected. Microspheres were also injected into an isolated-lung preparation in which vascular tone was increased with hypoxia. Microspheres did not induce vasodilatation, as reported in other vascular beds. Fluorescent microspheres were injected via tail veins into awake rats, and the spatial locations of the microspheres were determined. Regional distributions remained highly correlated when microspheres of one color were injected after microspheres of another color. This indicates that the initial injection did not alter regional perfusion. We conclude that, when used in appropriate numbers, 15-microm-diameter microspheres do not alter regional flow or vascular tone in the rat pulmonary circulation.

Adenosine↗
PubMed2001

Effects of ethylene oxide gas sterilization on physical properties of poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) microspheres.

The aggregation of poly(alpha-hydroxy acid) microspheres during ethylene oxide (EO) gas sterilization makes it difficult for the microspheres to be used in clinical applications. In this study, six kinds of PLLA-PEG-PLLA triblock copolymers (TriPLE) were synthesized with various composition ratios of PEG/PLLA in the range of 0.012 to 0.103. TriPLE microspheres were prepared by the oil-in-water emulsion method. TriPLE microspheres were characterized by using 1H-NMR, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). After sterilization by EO gas at 55 degrees C, the microspheres were analyzed by scanning electron microscope (SEM), laser diffractometry, standard sieves, X-ray diffraction (XRD), GPC, and DSC. When the composition ratio of PEG/PLLA was above 0.02, the initial crystallinity of TriPLE in microspheres was as high as 50%, and the microspheres were suitable to be sterilized by EO gas. On the other hand, TriPLE microspheres, which had composition ratios of PEG/PLLA below 0.02, had low initial crystallinities of about 30%, and aggregated during EO gas sterilization. For these microspheres, crystallinity increased up to 50% during the sterilization, whereas other TriPLE microspheres did not show any changes in crystallinity. Therefore, the aggregation of TriPLE microspheres during EO gas sterilization was markedly reduced as the initial crystallinity of TriPLE in the microspheres was increased.

Calorimetry, Differential Scanning↗
PubMed2001

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing.

The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce more new bone than would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary to fashion microsphere-loaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling. Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded microspheres by lyophilization, matrices for implantation were prepared by lyophilizing a suspension of the microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres. A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect well, allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology. In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days, with the unembedded microspheres releasing faster than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres in CMC was an effective implantable protein-delivery system for use in bone repair.

Animals↗
PubMed2003

Spray-dried carbamazepine-loaded chitosan and HPMC microspheres: preparation and characterisation.

In this study, the potential of the spray-drying technique for preparing microspheres able to modify the release profile of carbamazepine was investigated. Low-, medium- and high-molecular-weight chitosan and hydroxypropyl methylcellulose (HPMC) in different drug-polymer ratios were used for the preparation of microspheres. The microspheres, characterized by X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC), were also studied with respect to particle size distribution, drug content and drug release. The results indicated that the entrapment efficiency (EE), as well as carbamazepine release profile, depended on polymeric composition and drug-polymer ratios of the microspheres prepared. The best entrapment efficiencies were obtained when chitosan of low-molecular-weight (CL) or HPMC were used for the microencapsulation. For all types of polymer used, the microspheres with low carbamazepine loading (6.3% w/w) showed better control of drug release than the microspheres with higher drug loadings. The HPMC microspheres showed the slowest carbamazepine release profile with no initial burst effect. Carbamazepine release profiles from ternary systems, carbamazepine-CL-HPMC microspheres, depended mostly on HPMC content and showed similar carbamazepine release profile as CL microspheres when HPMC content was low (9:1 CL-HPMC ratio, w/w). Otherwise, the carbamazepine release from CL-HPMC microspheres was remarkably faster than from either chitosan or HPMC microspheres. The release profile of carbamazepine from the microspheres was highly correlated with the crystalline changes occurring in the matrix.

Anticonvulsants↗
PubMed2003

The influence of chitosan on in vitro properties of Eudragit RS microspheres.

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series. The average particle size of microspheres without chitosan, prepared at the same stirring rate, was smaller. Pipemidic acid content increased with increasing fraction particle size, but not with increasing stirring rate as it was observed for microspheres without chitosan. We presume that high pipemidic acid content in larger microspheres is a consequence of cumulation of undissolved pipemidic acid particles in larger droplets during microspheres preparation procedure. Pipemidic acid release was faster from microspheres with chitosan and no correlation between Higuchi dissolution rate constant and stirring rate or fraction particle size was found, though it existed in the system without chitosan. Structure and surface characteristics of microspheres observed by scanning electron microscope (SEM) were not changed significantly by incorporation of chitosan. But in contrast with microspheres without chitosan, the surface of chitosan microspheres was more porous after three hours of dissolution. It is supposed that the influence of particle size fraction and stirring rate on release characteristics is expressed to a great extent through porosity and indirectly through total effective surface area, but the incorporation of highly soluble component i.e. chitosan salt hides these effects on drug release. In conclusion, changes in biopharmaceutical properties due to varying stirring rate and fraction particle size exhibited the same direction as those reported for the microspheres without chitosan, although they are less expressed because of increased experimental variability, likely caused by chitosan.

Acrylic Resins↗
PubMedDate not supplied

Investigation of in-vitro release characteristics of NSAID-loaded polylactic acid microspheres.

The intra-pulmonary delivery of non-steroidal anti-inflammatory drug-loaded PLA microspheres has potential utility in the treatment of inflammatory lung conditions such as asthma. Drug encapsulation efficiency and release kinetics depend upon a variety of parameters in the production process, all of which affect the properties of the microspheres produced. The release of piroxicam from PLA microspheres followed an apparently biphasic release profile. PLA microspheres containing indomethacin, however, exhibited kinetics which approached more closely to zero order release. The effect of microsphere production parameters upon these release profiles has been investigated. Results indicate that factors affecting the nature of the microsphere matrix have the greatest influence on release profiles. The use of halothane as organic solvent in the microsphere production increases the burst release effect. Residual halothane is known to be present in the microspheres, producing a less stable matrix, thus allowing much faster release of the drug. The nature of drug incorporated also appears to affect the nature of the microspheres matrix. Piroxicam-loaded microspheres possess a much more porous matrix than indomethacin-loaded microspheres, as evidenced by washing procedures. This difference could explain the difference in release profiles between the two types of microspheres.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Effect of gamma-irradiation on peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) microspheres.

The effect of gamma-irradiation on the physicochemical properties of peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) (PLGA) microspheres was evaluated. PLGA (50/50, Mw: 8,600) with free carboxylic end groups was used to make drug-loaded and placebo microspheres by a solvent extraction evaporation method. Both formulated and non-formulated microspheres were gamma-irradiated at 0, 1, 1.5, and 2.5 Mrad doses. HPLC analysis based on extraction of peptide from the microspheres showed that peptide content of the microspheres was lowered upon irradiation and the reduction was more pronounced in formulated microspheres. The in-vitro release in 0.033M phosphate buffer, pH 7.0 at 37 degrees C (based on extraction of residual peptide) showed that the initial and subsequent release of peptide was higher in gamma-irradiated microspheres during the first 20 days. The difference became insignificant during the erosional controlled release of the peptide. There was no difference in release between the formulated and non-formulated microspheres of the nonirradiated or irradiated forms. Molecular weights (Mw and Mn), determined by size exclusion chromatography, were reduced by gamma-irradiation for both formulated and non-formulated placebo microspheres. Differential scanning calorimetry showed a gradual reduction in Tg of placebo microspheres but no reduction in peptide-loaded microspheres. In-vivo evaluation of the nonirradiated and the 1.5 Mrad irradiated microspheres showed no marked differences through 28 days. Since irradiation caused a lowering of Mw and Mn with the appearance of a low amount of unidentified substances, seemingly catalyzed by the polymer and the formulation excipients, gamma-irradiation sterilization of these parenteral delivery systems requires careful investigation on an individual product basis.

Gamma Rays↗
PubMed1987

Effects of hepatic arterial yttrium-90 microsphere administration alone and combined with regional bromodeoxyuridine infusion in dogs.

Brachytherapy by embolization with radiotherapeutic microspheres following intraarterial infusion of a radiosensitizer represents an attempt to combine several selective modalities into a more potent, focused attack on regionally confined tumors. In pursuit of this goal, we examined the ability of foxhounds with surgically implanted hepatic arterial (HA) delivery systems to tolerate a clinically relevant dosage of HA yttrium-90 (Y-90) by microsphere administration either alone or preceded by a 28-day constant HA infusion of either 5-bromo-2'-deoxyuridine (BUDR) or a control solution. Five dogs received BUDR (10 mg/kg/day) and five a control buffer infusion for 28 days immediately prior to the administration of Y-90-coated 15 micron resin microspheres (equivalent of 5000 rads to the entire liver) to each dog on day 31. In all animals, blood counts, bilirubin, amylase, appetite, weight, and behavior remained unchanged. Dogs receiving the microspheres after buffer infusion alone exhibited no hepatic enzyme alanine aminotransferase or alkaline phosphatase elevation. Alanine aminotransferase and alkaline phosphatase levels both rose during the third week of BUDR infusion, and while subsequent microsphere administration further increased enzyme levels, these levels had largely normalized by necropsy on day 82. At necropsy, the type and degree of hepatic toxicity among the animals receiving radioactive microspheres was comparable to that previously described in patients receiving external beam hepatic irradiation at conventional doses (2000-3000 rads). Also noted was a radiation-induced cholecystitis (due in large part to the gallbladder's total reliance on the hepatic artery for blood supply). One resin microsphere dog exhibited a small quantity of microspheres in the lungs causing focal radiation-induced granulomas suggesting the need to assess shunting of microspheres through the liver in clinical studies. Thus, HA Y-90 microspheres with BUDR can produce acceptable, nonlethal, and tolerable toxicities in this dog model suggesting that clinical studies of this combination are not likely to be contraindicated by synergistic toxicity. Although HA BUDR did not contribute significantly to the toxicity of the Y-90 microspheres, HA BUDR by itself administered uninterrupted for 4 weeks may, like HA FUDR (clinically), cause chemical hepatitis/cholangitis. The unexpected fragmentation of the resin spheres (albeit without myelosuppression) has led us to begin studies with a recently developed nondisruptible glass microsphere (ThereSphere) in which the Y-90 is part of the glass matrix and cannot leach.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine Transaminase↗