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PubMed2002

Chitin/PLGA blend microspheres as a biodegradable drug-delivery system: phase-separation, degradation and release behavior.

A novel chitin-based microsphere was developed for anti-cancer drug-delivery purpose in the present study. These biodegradable microspheres were prepared by directly blending chitin with different contents of poly(D,L-lactide-co-glycolide 50:50) (PLGA 50/50) in dimethylacetamide-lithium chloride solution, and following it by coagulating in water via wet phase inversion. Scanning electron microscopy (SEM) micrography of the blend microsphere showed that there are numerous PLGA particulates homogeneously dispersed in chitin matrix, suggesting the occurrence of obvious phase separation from the blended chitin and PLGA 50/50 phase due to their thermodynamic incompatibility. Degradation of the chitin/PLGA 50/50 blend microsphere depends on the surface erosion of chitin phase and bulk hydrolysis of PLGA phase, according to the examinations of SEM and differential scanning calorimetry studies. Weight loss of the chitin/PLGA 50/50 blend microsphere increases with the increase of chitin content in the microsphere. A two-phase drug-release model is observed from the release of chlorambucil from chitin/PLGA 50/50 blend microspheres. The initial stage of drug-release rate increases with the increased chitin content due to the hydration and surface erosion of hydrophilic chitin phase; however, the following stage of slow release is sustained for several days, mainly contributed by the bulk hydrolysis of hydrophobic PLGA phase. In conclusion, such a chitin/PLGA 50/50 blend microsphere is novel and interesting, and may be used as a special drug-delivery system.

Biocompatible Materials↗
PubMed2002

Polyphosphoester microspheres for sustained release of biologically active nerve growth factor.

Controlled delivery of neurotrophic proteins to a target tissue by biodegradable polymer microspheres has been explored widely for its potential applications in the treatment of various disorders in the nervous system. We investigated in this study the potential of polyphosphoester microspheres as carriers for the sustained release of nerve growth factor (NGF), a water-soluble neurotrophic protein. Two polyphosphoesters (PPEs), P(BHET-EOP/TC) and P(DAPG-EOP), as well as poly(lactide/glycolic acid) (PLGA), were used to fabricate microspheres by a W/O/W emulsion and solvent evaporation/extraction method. With bovine serum albumin as a model protein to optimize processing parameters. P(DAPG-EOP) microspheres exhibited a lower burst effect but similar protein entrapment levels and efficiencies when compared with those made of PLGA. Bioactive NGF could be released for at least 10 weeks from the P(DAPG-EOP) microspheres, as confirmed by a neurite outgrowth assay of the PC12 cells. These NGF containing microspheres were incorporated into the nerve guide conduits that were implanted to bridge a 10 mm gap in a rat sciatic nerve model. Two weeks after implantation, immunostaining with an antibody against the neurofilament protein confirmed the presence of axons at the distal end of regenerated cables within the NGF microsphere-loaded conduits. These results demonstrated the feasibility of using biodegradable PPEs for microencapsulation of NGF and provided a basis for future therapeutic application of the microspheres.

Animals↗
PubMed2003

Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair.

The limitations of current grafting materials have driven the search for synthetic alternatives for the regeneration of trabecular bone. A variety of biodegradable polymer foams composed of 85/15 poly(lactide-co-glycolide) (PLAGA) have been evaluated for such uses. However, structural limitations may restrict the clinical use of these scaffolds. We have developed a novel sintered microsphere scaffold with a biomimetic pore system equivalent to the structure of trabecular bone. By modifying processing parameters, several different sintered microsphere structures were fabricated. Optimization of the structure dealt with modifications to sphere diameter and heating time. Compressive testing illustrated a trend between microsphere diameter and modulus, where increased microsphere diameter resulted in decreased modulus. In addition, evaluation of the pore system showed a positive correlation between sphere diameter and pore diameter. Mercury porosimetry showed increased median pore size with an increased microsphere diameter. Heating time modifications showed that compressive modulus was dependent on the period of heating with longer heating times resulting in higher moduli. It was also shown that heating time did not affect the pore structure. Analysis of the structural data indicated that the microsphere matrix sintered for 4h at a temperature of 160 degrees C with a microsphere diameter of 600-710 microm resulted in an optimal, biomimetic structure with range in pore diameter of 83-300 microm, a median pore size of 210 microm, 35% porosity, and a compressive modulus of 232 MPa. An in vitro evaluation of human osteoblasts seeded onto the sintered matrix indicated that the structure was capable of supporting the attachment and proliferation of cells throughout its pore system. Immunofluorescent staining of actin showed that the cells were proliferating three-dimensionally through the pore system. The stain for osteocalcin was used and showed that cells maintained phenotypic expression for this bone specific protein. Through this work, it was shown that an osteoconductive PLAGA scaffold with a pore system used as a reverse template to the structure of trabecular bone could be fabricated through the sintered microsphere method.

Actins↗
PubMed2003

Preparation and characterization of poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) microspheres for controlled release of paclitaxel.

Microspheres of a new kind of copolymer, poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA), are proposed in the present work for clinical administration of an antineoplastic drug paclitaxel with hypothesis that incorporation of a hydrophilic PEG segment within the hydrophobic PLA might facilitate the paclitaxel release. Paclitaxel-loaded PLA-PEG-PLA microspheres of various compositions were prepared by the solvent extraction/evaporation method. Characterization of the microspheres was then followed to examine the particle size and size distribution, the drug encapsulation efficiency, the colloidal stability, the surface chemistry, the surface and internal morphology, the drug physical state and its in vitro release behavior. The effects of polymer types, solvents and drug loading were investigated. It was found that in the microspheres the PEG segment was homogeneously distributed and caused porosity. Significantly faster release from PLA-PEG-PLA microspheres resulted in comparison with the PLGA counterpart. Incorporation of water-soluble solvent acetone in the organic solvent phase further increased the porosity of the PLA-PEG-PLA microspheres and facilitated the drug release. A total of 49.6% sustained release of paclitaxel within 1 month was achieved. Potentially, the presence of PEG on the surface of PLA-PEG-PLA microspheres could improve their biocompatibility. PLA-PEG-PLA microspheres could thus be promising for the clinical administration of highly hydrophobic antineoplastic drugs such as paclitaxel.

Absorbable Implants↗
PubMed1999

Uptake of orally administered polystyrene latex and poly(D,L-lactic/glycolic acid) microspheres into intestinal lymphoid tissues in chickens.

Fluorescein-labeled microspheres were orally administered to chickens and their distribution in intestinal lymphoid tissues was investigated. Polystyrene latex microspheres were observed in Peyer's patches, and also in the Meckel's diverticulum and the jejunum. Their density, however, seemed to be lower than that in Peyer's patches. Microspheres were rarely observed in the other intestinal tissues examined, including the bursa of Fabricius. Of note is that, although microspheres were present in the lumen, few, if any, were observed in the lamina propria of the caecal tonsil and caecum. Polystyrene latex microspheres of diameter 2.0 microm or 4.5 microm were also observed in Peyer's patches, but their density seemed to be lower as compared with the 0.75 microm microspheres. Poly(D,L-lactic/glycolic acid) (PLGA) microspheres were prepared using PLGAs of various molecular weights (MW) and their uptake into Peyer's patches was compared. Microspheres prepared with PLGA of average MW of 20000 were not taken up into Peyer's patches, but those prepared with PLGA of average MW of 61000 or 99 800 were taken up into Peyer's patches.

Administration, Oral↗
PubMed2001

Investigation on a novel core-coated microspheres protein delivery system.

Among the different approaches to achieve protein delivery, the use of polymers, specifically biodegraded, holds great promise. In this work, a new microsphere delivery system composed of alginate microcores surrounded by a biodegradable poly-DL-lactide-poly(ethylene glycol (PELA) was designed to improve the loading efficiency and stability of proteins. Alginate was solidified by calcium (MS-1), polylysine (MS-2) and chitosan (MS-3), respectively, to form different microcores. Human Serum Albumin (HSA), used as a model protein, was efficiently entrapped within the alginate microcores using a high-speed stirrer and then microencapsulated into PELA copolymer using a w/o/w solvent extraction method. DSC analysis of the microspheres revealed the efficient encapsulation of the alginate microcores, while the microcores were dispersed in the PELA matrix. SDS-PAGE results showed that HSA kept its structural integrity during encapsulation and release procedure. Microspheres were characterized in terms of morphology, size, loading efficiency, in vitro degradation and protein release. The degradation profiles were characterized by measuring the loss of microsphere mass, the decrease of polymer intrinsic viscosity and the reduction of PEG content of PELA coat. The release profiles were investigated from the measurement of protein presented in the release medium at various intervals. The results were that the degradation rate of these core-coated microspheres was MS-2>MS-1>MS-3. The extent of burst release from the core-coated microspheres in the initial protein release was lower than the 27% burst release from the conventional microspheres. In conclusion, the work presents a new approach for macromolecular drugs (such as protein, peptide drugs) delivery. The core-coated microspheres system may have potential use as a carrier for drugs that are poorly absorbed after oral administration.

Alginates↗
PubMed2001

Enhanced pulmonary absorption following aerosol administration of mucoadhesive powder microspheres.

Mucoadhesive, hydroxypropylcellulose (HPC) microspheres were prepared for powder inhalation and their feasibility for enhancing pulmonary drug absorption was investigated. Respirable-sized microspheres, incorporating crystalline or amorphous fluorescein (used as a model drug), were prepared by spray-drying aqueous or ethanol HPC systems, respectively. These were prepared from a variety of HPC grades (SL, L, M and H types) in different fluorescein-HPC ratios (1:1-1:10). The microspheres were administered to tracheally-intubated guinea pigs as powder aerosols and their fluorescein pharmacokinetics studied, and compared to those for pure crystalline fluorescein ('control'). All microspheres were prepared and aerosolized within a MMAD range of 1.3-2.6 microm (GSD< or =2.1). Fluorescein's dissolution was increased in the amorphous form by 6.5-fold when compared to the crystalline material (83.9-87.2 vs. 13.5 microg/ml, respectively). Poor dissolution for the 'control' crystalline fluorescein appeared to be rate-determined, which showed bi-phasic absorption profiles (T(max)=60 min), simultaneously competing with mucociliary clearance out of the lower airways. While the crystalline/HPC microspheres prolonged absorption, the amorphous fluorescein/HPC microspheres showed rapid absorption with T(max)=0 min (immediately after the administration had terminated). This was explained by enhanced fluorescein dissolution and was consistently observed irrespective of the fluorescein-HPC ratio or HPC grade. However, the microspheres with the least viscous HPC-SL and the lowest fluorescein-HPC ratio (1:1) failed to enhance bioavailability, presumably because the mucociliary clearance was undisturbed. In contrast, the microspheres with the highly viscous HPC-H with ratios > or = 1:4 successfully enhanced absorption, achieving 88.0% bioavailability by virtue of HPC increasing the dissolution and retarding the mucociliary clearance.

Absorption↗
PubMed2002

Characterization of the initial burst release of a model peptide from poly(D,L-lactide-co-glycolide) microspheres.

In order to study the mechanism of initial burst release from drug-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres, a model peptide, octreotide acetate, was encapsulated in PLGA 50/50 (M(w) approximately 50,000) microspheres using a double emulsion-solvent evaporation method. A simple and accurate continuous monitoring system was developed to obtain a detailed release profile. After different incubation times in the release medium, the morphology and permeability of the microspheres were examined using scanning electron and confocal microscopy (after immersing the microspheres in a fluorescent dye solution for 30 min), respectively. Both the external and internal morphology of the microspheres changed substantially during release of >50% of the peptide over the first 24 h into an acetate buffer, pH 4 at 37 degrees C. After 5 h, a 1-3 microm "skin" layer with decreased porosity was observed forming around the microsphere surface. The density of the "skin" appeared to increase after 24 h with negligible surface pores present, suggesting the formation of a diffusion barrier. Similar morphological changes also occurred at pH 7.4, but more slowly. Correlated with these results, the confocal microscopy studies (at pH 4) showed that the amount of dye penetrated inside the microspheres sharply decreased with time. In summary, over the first 24 h of drug release, a non-porous film forms spontaneously at the surface of octreotide acetate-loaded PLGA microspheres in place of an initially porous surface. These rapid alterations in polymer morphology are correlated with a sharp decline in permeability and the cessation of the initial burst.

Biocompatible Materials↗
PubMed1999

Optimization of preparative conditions for poly-DL-lactide- polyethylene glycol microspheres with entrapped Vibrio cholera antigens.

Poly-dl-lactide-polyethylene glycol (PELA) with different contents of polyethylene glycol(PEG) were synthesized and the PEG content was estimated according to the integral height of hydrogen shown in 1H-NMR. PELA microspheres containing V. cholera antigen, outer membrane protein (OMP) were prepared by a water-in-oil-in-water (W/O/W) based on solvent evaporation procedure. Antigen microspheres with smooth surface, suitable size for oral administration (0.5-5 microm), high loading efficiency (about 60%) and low level of residual solvent (lower than 20ppm) were obtained. Microspheres prepared from PELA with PEG content of about 10% achieved the highest loading efficiency among PELA copolymers and poly-dl-lactide (PLA) homopolymer, which suggested that microspheres size, morphology and the precipitation rate of polymer showed considerable relations with OMP loading efficiency. The regulation of the solvent components of the oil phase contributes to a stable emulsion W/O, and it is concluded that the stable emulsion W/O plays a significant role in improving the protein loading efficiency of obtained microspheres. The addition of stabilizer, such as gelatin and polyvinyl alcohol, into the internal water phase before emulsification produced no significant difference in OMP entrapment and microspheres size. A higher OMP loading efficiency was achieved by adding NaCl or adjusting the pH at the iso-electric point of OMP in the external water phase. It was indicated in vitro that PELA microspheres with smaller size showed larger extent of initial release and higher release rate, whereas microspheres with the diameter of 2.17 microm showed no apparent burst effect.

Antigens, Bacterial↗
PubMed1999

Tetracycline-HCl-loaded poly(DL-lactide-co-glycolide) microspheres prepared by a spray drying technique: influence of gamma-irradiation on radical formation and polymer degradation.

Tetracycline-HCl (TCH)-loaded microspheres were prepared from poly(lactide-co-glycolide) (PLGA) by spray drying. The drug was incorporated in the polymer matrix either in solid state or as w/o emulsion. The spin probe 4-hydroxy-2,2,6, 6-tetramethyl-piperidine-1-oxyl (TEMPOL) and the spin trap tert-butyl-phenyl-nitrone (PBN) were co-encapsulated into the TCH-loaded and placebo particles. We investigated the effects of gamma-irradiation on the formation of free radicals in polymer and drug and the mechanism of chain scission after sterilization. Gamma-Irradiation was performed at 26.9 and 54.9 kGy using a 60Co source. The microspheres were characterized especially with respect to the formation of radicals and in vitro polymer degradation. Electron paramagnetic resonance (EPR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), high-performance liquid chromatography (HPLC), gas chromatography-mass spectroscopy (GC-MS), and scanning electron microscopy (SEM) were used for characterization of the microspheres. Using EPR spectroscopy, we successfully detected gamma-irradiation induced free radicals within the TCH-loaded microspheres, while unloaded PLGA did not contain radicals under the same conditions. The relatively low glass transition temperature of the poly(dl-lactide-co-glycolide) (37-39 degrees C) seems to favor subsequent reactions of free radicals due to the high mobility of the polymeric chains. Because of the high melting point of TCH (214 degrees C), the radicals can only be stabilized in drug loaded microspheres. In order to determine the mechanism of polymer degradation after exposure to gamma-rays, the spin trap PBN and the spin probe TEMPOL were encapsulated in the microspheres. gamma-Irradiation of microspheres containing PBN resulted in the formation of a lipophilic spin adduct, indicating that a polymeric radical was generated by random chain scission. Polymer degradation by an unzipping mechanism would have produced hydrophilic spin adducts of PBN and monomeric radicals of lactic or glycolic acid. These degradation products were not detected by EPR. This result is confirmed by the observation that possible diamagnetic reaction products of low molecular weight, consisting of TEMPOL and lactide or glycolide monomers, could not be detected by GC-MS. While an irradiation dose-dependent decrease in molecular weight of PLGA could be verified in agreement with the literature, TCH content of the microspheres was not affected by the exposure to gamma-rays. It can be concluded that EPR spectroscopy in combination with GPC, DSC, and HPLC allows a detailed characterization of the impact of gamma-sterilization on biodegradable parenteral drug delivery systems.

Anti-Bacterial Agents↗
PubMed1998

Analysis of local and systemic immunological responses after intra-tracheal, intra-nasal and intra-muscular administration of microsphere co-encapsulated Yersinia pestis sub-unit vaccines.

Intra-tracheal, intra-nasal and intra-muscular immunisation with admixed Y. pestis sub-units (3 micrograms V, 0.47 microgram F1) or equivalent doses of poly-L-lactide microsphere co-encapsulated antigens was done. Systemic and mucosal responses to F1 and V differed according to immunisation route, and encapsulated status of the sub-units. Irrespective of immunisation site, particulated sub-units stimulated statistically superior primary systemic reactions, with intra-tracheal and nasal microsphere immunisations eliciting superior serum anti-V IgG titres in comparison to intra-muscular injection of free vaccines (p < 0.001 beyond day 8). Pulmonary and nasal delivery of microspheres induced primary serum anti-V IgG titres which were greater (p < 0.039) or equal to (p > 0.056) those after intra-muscular injection of spheres. In terms of serum anti-F1 titres, mice responded best to intra-muscular, and comparatively poorly to intra-nasal immunisations. Intra-tracheal administration of microspheres induced strongest responses in the respiratory tract, dominated by the IgG rather than IgA isotype. An intra-nasal booster immunisation on day 63 potentiated strong local and circulating anti-V IgG titres in microsphere vaccinees. Priming and boosting with free vaccines induced significantly depressed secondary serum anti-F1 titres relative to microsphere immunisations (p < 0.024 at days 78 and 120). In contrast to other priming sites, intra-tracheal instillation of encapsulated vaccines facilitated the induction of IgG antibody to both F1 and V in day 146 broncho-alveolal washings. With the exception of primary responses to F1 in mice immunised intra-tracheally with microspheres, IgG1 was the dominant subclass of anti-F1/V IgG in serum. We conclude that introduction of biodegradable microspheres containing the F1 and V sub-units into to the upper or lower respiratory tract engenders immune responses of a magnitude comparable with that induced by parenteral immunisation, and may present a means of protecting individuals from plague.

Administration, Intranasal↗
PubMed1999

Biodegradable microspheres containing influenza A vaccine: immune response in mice.

A monovalent influenza split vaccine was microencapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) and ABA triblock copolymers using a W/O/W double emulsion technique. To stabilize the antigen, influenza vaccine was also coencapsulated with liposomes. Antigen release from microspheres was determined in vitro using a hemagglutinin-specific ELISA. PLGA-microspheres with liposomes released immunoreactive hemagglutinin in a pulsatile manner, a preferred feature for the development of a single dose vaccine delivery system. Influenza hemagglutinin specific IgG and neutralizing antibody responses were studied in BALB/c mice following subcutaneous injection of different microsphere preparations. PLGA-microspheres elicited a significantly higher primary IgG response compared to nonencapsulated antigen. ABA-microspheres seemed to be less immunogenic than PLGA-microspheres based on the IgG antibody response, however, similar levels of neutralizing antibodies were observed after eight weeks with both polymers. Entrapment of the antigen in liposomes prior to microencapsulation did not further enhance the immune response. The immunopotentating effect of the antigen-loaded microspheres was prominently enhanced when they were given as suspension in fluid antigen, suggesting that free antigen may serve as priming and microencapsulated antigen as booster dose. Eight weeks after a single subcutaneous immunization with PLGA or ABA-microspheres neutralizing antibodies were as high as those obtained after two subcutaneous administrations of fluid vaccine four weeks apart. Microencapsulated influenza antigen may have potential for a single dose vaccine delivery system with adjuvant properties.

Animals↗
PubMed2001

Effects of the rate of solvent evaporation on the characteristics of drug loaded PLLA and PDLLA microspheres.

We investigated the effects of the rate of solvent removal by varying ambient pressure at a fixed temperature on the morphology, particle sizes, drug encapsulation efficiency and releases pattern of lidocaine loaded poly-L-lactatide (PLLA) and poly-D,L-lactatide (PDLLA) microspheres, prepared with O/W emulsion-solvent evaporation process. Prepared in the fast rate of solvent evaporation (FRSE) process by reducing ambient pressure, smoothly morphological surface of drug loaded PLLA and PDLLA microspheres was observed. While in the normal rate of solvent evaporation (NRSE) process, roughness or pinhole surface was only found at drug loaded PLLA microspheres. Fabricated in the FRSE process, both PLLA and PDLLA microspheres showed smaller particle sizes and lower drug encapsulation efficiencies than those prepared in NRSE process. In regard to two materials, PLLA microspheres had higher drug encapsulation efficiencies than PDLLA ones for both processes. Although initial burst releases of drug were observed for both PLLA and PDLLA microspheres prepared in whatever solvent removal process, drug release for PLLA microspheres was slightly less than that for PDLLA ones in the earlier stage of drug release. However, in the subsequent stage of drug release, there was no difference between two materials. In corporation with different crystalline characteristics of PLA polymer and its derivatives, FRSE process by reducing ambient pressure could be further applied to produce different characteristics of microspheres for drug delivery.

Lidocaine↗
PubMed2002

Stomach-specific anti-H. pylori therapy. I: Preparation and characterization of tetracyline-loaded chitosan microspheres.

The main objective of the study was to develop a stomach-specific drug delivery system to increase the efficacy of tetracycline against Helicobacter pylori. Chitosan microspheres were prepared by ionic cross-linking and precipitation with sodium sulfate. Two different methods were used for drug loading. In method I, tetracycline was mixed with chitosan solution before the simultaneous cross-linking and precipitation. In method II, the drug was incubated with pre-formed microspheres for 48 h. The cumulative amount of tetracycline that was released from chitosan microspheres and the stability of the drug was examined in different pH medium at 37 degrees C. Microspheres with a spherical shape and an average diameter of 2.0-3.0 microm were formed. When the drug was added to the polymer solution before cross-linking and precipitation only 8% (w/w) was optimally incorporated in the final microsphere formulation. When the drug was incubated with the pre-formed microspheres, on the other hand, a maximum of 69% (w/w) could be loaded. Thirty percent of tetracycline either in solution or when released from microspheres was found to degrade at pH 1.2 in 12 h. The preliminary results from this study suggest that chitosan microspheres can be used to incorporate antibiotic drugs and may be effective when administered locally in the stomach against H. pylori.

Anti-Bacterial Agents↗
PubMed2002

Drug release properties of pectinate microspheres prepared by emulsification method.

This study explored the potential of pectin for use in making microspheres for sustained-release of drugs. The pectin microspheres were prepared by external gelation using an emulsification technique with calcium chloride as the crosslinking agent. The influences of drug core (sulphanilamide, sulphaguanidine and sulphathiazole) and dissolution media (distilled water, USP HCl and phosphate buffers) on the drug release properties of the pectinate microspheres were examined. The morphology and drug content of the microspheres, and the solubility and solution pH of the drugs were also determined. Pectinate microspheres were successfully prepared by the emulsification technique. The rate of drug released from microspheres was highest in USP HCl buffer, followed by USP phosphate buffer and distilled water. Interestingly, the lowest percentage of drug released was produced by microspheres which were smallest in size and therefore largest in specific surface area, and consisting of sulphanilamide, the most water soluble drug. Further investigation showed that the microspheres consisted of both bound and unbound drugs. The percentage of drug released was predominantly determined by the relative contents of bound and unbound drugs embedded in the pectinate matrix.

Anti-Infective Agents↗
PubMed2003

Preparation of sustained-release nitrendipine microspheres with Eudragit RS and Aerosil using quasi-emulsion solvent diffusion method.

Sustained-release nitrendipine microspheres were prepared in liquid system by quasi-emulsion solvent diffusion method, in which the Aerosil was employed as an inert dispersing carrier to improve the dissolution rate of nitrendipine, and Eudragit RS as a retarding agent to control the release rate. The resultant microspheres were evaluated for the recovery, bulk density, average particle size, drug loading, and incorporation efficiency. And the factors affecting the formation of microspheres and the drug-release rate were investigated. It was observed by a scanning electron microscope (SEM) that the microspheres were finely spherical and uniform, and no entire nitrendipine crystals were observed visually. The results of X-ray diffraction indicated that nitrendipine in microspheres was disordered, suggesting that nitrendipine was highly dispersed in microspheres. The drug loading of microspheres was enhanced with increasing the ratio of drug to excipients, and the incorporation efficiency was always >90%. The formation of microspheres was mainly influenced by the amount of bridging liquid and sodium dodecyl sulfate (SDS) in poor solvent. The dissolution profiles could be modulated with adjusting the amount of retarding agent and dispersing carrier formulated.

Acetone↗
PubMed2003

Lung-targeting microspheres of carboplatin.

Carboplatin (CPt) was incorporated in the gelatin microspheres by the method of emulsion and the drug content determined spectrophotometrically. The arithmetic mean diameter of the microspheres was 13.20 microm with 98% of the microspheres ranging from 5.0 to 28.6 microm. The average carboplatin content was 23.76% and the yield of the microspheres 85.12%. The microspheres were stable for three months when stored at 37 degrees C/RH 75%, showing insignificant change in appearance and drug content. The in vitro release profile of the microspheres could be described by a biexponential equation, and the release t(1/2) was 49.7 min and 92.04% released in 10h; while for the original drug, CPt, under the same conditions, 92.15% released in the first half an hour. Very high lung-targeting efficiency in vivo was proved by the results of targeting parameters. The S-180 lung neoplasm models were established by i.v. cancer cells in mice and the number of pulmonary nodules examined for evaluation of the treatment effect. The results of therapeutic tests showed that the antitumour effects were increased by injection of the microspheres compared with the injection of CPt solution: half of the dose in the microspheres showed comparable effect to the original drug.

Animals↗
PubMed2002

Influence of injection site, microvascular pressure and ultrasound variables on microbubble-mediated delivery of microspheres to muscle.

OBJECTIVES: Our objective was to test the hypothesis that the ultrasound pulsing interval (PI), microbubble injection site and microvascular pressure significantly influence the transport of 100-nm microspheres to muscle through extravasation sites created by the destruction of microbubbles with ultrasound. BACKGROUND: Microbubbles show promise as targeted drug and gene delivery agents; however, designing optimal microbubble-based therapies will require an understanding of the factors that influence the transport of microbubble-delivered, gene-bearing vehicles to tissue. METHODS: Ultrasound at 1 MHz, with a peak negative pressure amplitude of 0.75 MPa, was applied to microbubbles and 100-nm microspheres in exteriorized rat spinotrapezius muscle. Ultrasound PIs of 1, 3, 5 and 10 s, arterial microsphere injection times of 10 or 40 s and arterial versus venous injection sites were tested. RESULTS: Extravasation point creation and microsphere delivery were greatest when the ultrasound PI was 5 or 10 s. No significant differences in extravasation point creation or microsphere delivery were observed with arterial versus venous microbubble injection, but a trend toward increased microsphere delivery with arterial injection may exist. Decreasing the arterial injection time from 40 to 10 s increased microvascular pressure, which, in turn, substantially enhanced microsphere transport to tissue, without a concomitant increase in the number of extravasation points. CONCLUSIONS: The ultrasound PI and microvascular pressure significantly influence the creation of extravasation points and the transport of microspheres to tissue. These factors may be important in designing and optimizing contrast ultrasound-based therapies.

Animals↗