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PubMed2005

Heating and coagulation volume obtained with high-intensity focused ultrasound therapy: comparison of perflutren protein-type A microspheres and MRX-133 in rabbits.

PURPOSE: To compare the efficiency of different microbubble contrast agents in the heating and coagulation of rabbit liver tissue by using high-intensity focused ultrasound therapy. MATERIALS AND METHODS: The use of and protocols for Japan white rabbits were approved by the University of Tokyo Committee on Animal Resources. In vitro experiments were conducted in a 1-mL cylindric space of polyacrylamide gel, which contained different microbubble contrast agents (MRX-133 or perflutren protein-type A microspheres). In vivo experiments were performed in six Japan white rabbits (two for the perflutren protein-type A microsphere group, two for the MRX-133 group, and two for the control group). In each rabbit, the liver was directly subjected to high-intensity focused ultrasound after intravenous injection of different microbubble contrast agents. Natural saline was used as a control. High-intensity focused ultrasound was applied for 30 seconds by using a 2.18-MHz transducer, and the temperature increase and volume of coagulation necrosis were evaluated. Statistical analysis was performed by using an analysis of variance test, which was followed by a Student-Newman-Keuls test; a P value of <.05 was considered to indicate a statistically significant difference. RESULTS: In the MRX-133 group, the mean temperature increase was significantly greater and faster than that in the control group (P < .01) or in the perflutren protein-type A microsphere group (P < .05). In the perflutren protein-type A microsphere group, the mean temperature increase was greater and faster than that of the control group (P < .01) for both in vitro and in vivo experiments. The mean volume of the coagulation necrosis lesion was 117.9 mm3 +/- 48.4 (+/-standard deviation) for the MRX-133 group, 45.4 mm3 +/- 24.9 for the perflutren protein-type A microsphere group, and 17.7 mm3 +/- 9.0 for the control group. In the MRX-133 group, the mean volume of coagulation necrosis was significantly greater than that of the control or the perflutren protein-type A microsphere group (P < .01), and in the perflutren protein-type A microsphere group, the volume of coagulation necrosis was greater than that of the control group (P < .05). CONCLUSION: MRX-133 had greater efficiency than perflutren protein-type A microspheres in high-intensity focused ultrasound-induced heating and coagulation of rabbit liver tissue.

Animals↗
PubMed1988

Microsphere estimates of blood flow: methodological considerations.

The microsphere technique is a standard method for measuring blood flow in experimental animals. Sporadic reports have appeared outlining the limitations of this method. In this study we have systematically assessed the effect of blood withdrawals for reference sampling, microsphere numbers, and anesthesia on blood flow estimates using radioactive microspheres in dogs. Experiments were performed on 18 conscious and 12 anesthetized dogs. Four blood flow estimates were performed over 120 min using 1 X 10(6) microspheres (15 microns) each time. The effects of excessive numbers of microspheres (13 million), pentobarbital sodium anesthesia (30 mg/kg), and replacement of volume loss for reference samples with dextran 70 were assessed. In both conscious and anesthetized dogs a progressive decrease in gastric mucosal blood flow and cardiac output was observed over 120 min. This was also observed in the pancreas in conscious dogs. The major factor responsible for these changes was the volume loss due to reference sample withdrawals. Replacement of the withdrawn blood with dextran 70 led to stable blood flows to all organs. The injection of excessive numbers of microspheres did not modify hemodynamics to a greater extent than did the injection of 4 million microspheres. Anesthesia exerted no influence on blood flow other than raising coronary flow. We conclude that although blood flow to the gastric mucosa and the pancreas is sensitive to the minor hemodynamic changes associated with the microsphere technique, replacement of volume loss for reference samples ensures stable blood flow to all organs over a 120-min period.

Animals↗
PubMed1996

Measurement of regional myocardial blood flow in rats by unlabeled microspheres and Coulter channelyzer.

A relatively inexpensive, expeditious, new nonradioactive microsphere method for measuring regional myocardial blood flow (RMBF) was developed with unlabeled microspheres and a Coulter Channelyzer. To validate the efficiency of this method, hearts from rats were perfused ex vivo by retrograde aortic cannulation. Unlabeled microspheres of varying size were injected into a side arm in the aortic cannula or added to blood samples collected from the rats. Microspheres were then recovered from the cardiac tissue and blood samples. It was found that > 97% of perfused microspheres (diam > 9.4 microns) were retained in the myocardium and that 94.8 +/- 2.2% of the trapped microspheres were recovered and counted successfully using a Counter Channelyzer. The percent recovery of microspheres from 2- and 0.5-ml blood samples were 95.4 +/- 2.3 and 95.3 +/- 3.1%, respectively. Blood flow to the anterior and posterior halves of the ventricular free walls and septum were measured in six rats; excellent agreements were found between the results yielded by 10-, 15-, and 20-microns unlabeled microspheres injected simultaneously. The transmural flow gradients in the left ventricular free wall estimated by 10- and 15-microns spheres did not significantly differ from each other. Thus the method developed here provides a new alternative for measurement of RMBF, which currently allows at least three measurements for nontransmural gradient RMBF and at least two measurements for transmural gradient RMBF.

Animals↗
PubMed1988

Measurement of bronchial blood flow with radioactive microspheres in awake sheep.

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Myocardial micronecrosis produced by microsphere embolization. Role of an alpha-adrenergic tonic influence on the coronary microcirculation.

Microspheres approximately 25 or 50 micrometers in diameter were systemically embolized from the left ventricular cavity. The number of microspheres given was empirically chosen to minimize the possibility of more than one microsphere lodging in an arteriole (3 mg/kg), yet was sufficient to allow for adequate histological assessment. The dogs were sacrificed after 24 hours, and focal areas of myocytolytic necrosis were noted in the myocardium. Groups of dogs were given pretreatment with drugs 10 minutes before embolization. Dogs pretreated with phentolamine (n = 8) and prazosin (n = 2) did not reveal any areas of myocardial necrosis after embolization with 25-micrometers microspheres. Cardiac lesions were also prevented in four of five dogs pretreated with verapamil. In contrast, cardiac lesions were not prevented by pretreatment with yohimbine (n = 2), dipyridamole (n = 3), propranolol (n = 2), or atropine (n = 2). Drug pretreatment with phentolamine or verapamil was not able to prevent cardiac lesions after embolization with 50-micrometers microspheres. Furthermore, despite a greater number of microspheres physically present in the subendocardial layer, the necrotic lesions were more frequent in the mid-wall and epicardial layers. Lesions produced by 25- or 50-micrometers emboli were also significantly smaller in the endocardium. Systemic embolization with microspheres excluding the coronary circulation did not produce cardiac lesions. We conclude that mechanical interruption of the coronary circulation with a 25-micrometers microsphere may be a necessary but not sufficient condition to produce cardiac necrosis. An alpha 1-adrenergic mechanism is also involved in the production of these lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed2000

Phase transfer and characterization of poly(epsilon-caprolactone) and poly(L-lactide) microspheres.

A method suitable for transfer of poly(epsilon-caprolactone) and poly(L-lactide) microspheres (synthesized by pseudoanionic dispersion polymerization of epsilon-caprolactone and L-lactide in heptane-1,4-dioxane mixed solvent) from heptane to water was developed. This method consists of treating the microspheres with KOH-ethanol in the presence of surfactants (nonionic Triton X-405, anionic sodium dodecyl sulfate (SDS), and zwitterionic ammonium sulfobetaine-2 (ASB)). Partial hydrolysis of polyesters results in the formation of hydroxyl and carboxyl groups in the surface layer of microspheres and enhances their stability in water-based media. Minimal concentrations of surfactants, needed to obtain stable suspensions of particles, were equal to 3 x 10(-2) and 6 x 10(-2), and 3 x 10(-2) mol l(-1) for Triton X-405. SDS, and ASB, respectively. In the case of poly(epsilon-caprolactone) microspheres, suspensions in water were stable for all three surfactants for pH values ranging from 3 to 11. Suspensions of poly(L-lactide) were stable in the same range of pH values only for ASB. Surface charge density determined by electrophoretic mobility varied for poly(epsilon-caprolactone) microspheres from 2.6 x 10(-7) to 8.9 x 10(-7) mol m(-2), for particles stabilized with Triton X-405 and ASB. respectively. In the case of poly(L-lactide) microspheres, surface charge density varied from 3.9 x 10(-7) (stabilizer: Triton X-405) to 7.4 x 10(-7) mol m(-2) (stabilizer: ASB). Carboxyl groups located in the surface layer of poly(L-lactide) microspheres were used for covalent immobilization of 6-aminoquinoline, a fluorophore with an amino group. Maximum surface concentration of immobilized 6-aminoquinoline was equal to 1.9 x 10(-6) mol m(-2). Poly(epsilon-caprolactone) microspheres transferred into water were loaded with ethyl salicylate. Loading up to 38% (w/w) was obtained.

Biocompatible Materials↗
PubMed2001

Controlled release of lysozyme from succinylated gelatin microspheres.

Gelatin was anionized to increase the carboxylic acid groups through succinylation. Succinylation of gelatin was performed using varying amounts of succinic anhydride. This gave various percentages of substitution. Lysozyme, a cationic antibacterial enzyme, which has important applications in the reduction of prosthetic valve endocarditis, was chosen as a model protein drug. Microspheres were prepared using unmodified gelatin and succinylated gelatin (SG) and lysozyme was incorporated into them. The percentage loading and release profiles of lysozyme for gelatin and SG microspheres were evaluated and compared. It was found that the SG microspheres exhibited higher loading efficiency for lysozyme (50%) than the unmodified gelatin microspheres. The in vitro release of lysozyme from SG microspheres occurred up to 122 h, compared to 96 h for gelatin microspheres, for the release of most of the lysozyme incorporated. This prolonged release of lysozyme from SG microspheres was attributed to the electrostatic interaction between the cationic lysozyme and the anionic SG microsphere carrier.

Biocompatible Materials↗
PubMed2005

Submucosal injection of poly(lactic-co-glycolic acid) microspheres in rabbit bladder as a potential treatment for urinary incontinence and vesicoureteral reflux: preliminary results.

Endoscopic injection of bulking agents has been gaining attention as a therapy for urinary incontinence and vesicoureteral reflux because this therapy is simpler, less operation time-consuming and less painful than traditional surgical operations. The ideal bulking agent for the injection therapies must be easily injectable, biocompatible, volume-stable, non-antigenic and non-migratory. We evaluated poly(lactic-co-glycolic acid) (PLGA) microspheres as an injectable bulking agent for urologic injection therapies. To determine whether PLGA microspheres meet the requirements of an ideal bulking agent, PLGA microspheres were injected into the submucosal sites of a rabbit bladder wall. The microspheres were easily injectable. Two and five weeks post-implantation, histological examinations indicated that host cells from the surrounding bladder tissues migrated to the space between the injected microspheres and formed new hybrid tissue structures. Lymphocyte migration was noted around the implanted microspheres, but the inflammatory reaction diminished at 5 weeks. The hybrid tissue volume did not significantly decrease over time. There was no evidence of microsphere migration to the distant organs. Although long-term studies are needed to evaluate the therapeutic potential of this method, these preliminary results suggest the possibility of PLGA microspheres as a potentially useful injection material for urinary injection therapies.

Animals↗
PubMed2002

Polystyrene microspheres as a specific marker for the diagnosis of aspiration in hamsters.

The diagnosis of recurrent aspiration in young children is problematic because there is no specific gold standard test to be used. In the present work, normal saline or a suspension of white polystyrene microspheres in normal saline was instilled into hamsters' trachea (n = 42), and bronchoalveolar lavage (BAL) cytology, microsphere index (total microspheres/100 macrophages), and lung histology were followed for 90 d. Naive animals (n = 6) had no tracheal instillation. On Days 1, 3, 10, 32, 60, and 90 after tracheal instillation, animals were killed (saline-instilled animals, n = 3; and microsphere-instilled animals, n = 4), and BAL was performed. There was a marked inflammatory response in BAL on Day 1 after tracheal instillation of saline or microsphere suspension. White microspheres were clearly identified within alveolar macrophages in all studied days. Microsphere numbers showed a 50% disappearance rate of 10 d. A mild peribronchial inflammation was noted in lung histology only on Day 1 after instillation. Microspheres were not detected in extrapulmonary organs. We conclude that polystyrene microspheres instilled in hamsters' trachea can be easily identified in BAL macrophages for as long as 3 mo and could potentially be used as a sensitive, specific, and stable marker for the diagnosis of aspiration.

Animals↗
PubMed2003

Periocular injection of microspheres containing PKC412 inhibits choroidal neovascularization in a porcine model.

PURPOSE: Oral administration of PKC412, a kinase inhibitor that blocks several isoforms of protein kinase C (PKC) and receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor, and stem cell factor, inhibits ocular neovascularization in a murine model. The purpose of this study was to determine whether sustained local delivery of PKC412 in a human-sized eye inhibits choroidal neovascularization (CNV). METHODS: Laser photocoagulation was used to rupture Bruch's membrane in young domestic pigs, and then a periocular injection of control microspheres or microspheres containing 25% or 50% PKC412 was given. After 10 days the integrated area of CNV at Bruch's membrane rupture sites was measured by image analysis. The levels of PKC412 in choroid, retina, and vitreous were measured either 10 or 20 days after periocular injection of 50% PKC microspheres or at 20 days after injection of 25% PKC412 microspheres. RESULTS: The areas of CNV at Bruch's membrane rupture sites were significantly smaller in eyes that received a periocular injection of microspheres containing 25% (P=0.0042) or 50% (P=0.0012) PKC412 than those in eyes injected with control microspheres. Ten days after periocular injection of 50% PKC412 microspheres, PKC412 was detected in the choroid, but not in the retina or vitreous. Twenty days after periocular injection of 50% PKC412, high levels of PKC412 were measured in the choroid, vitreous, and retina. Levels were lower but still substantial in all three compartments 20 days after periocular injection of 25% microspheres. CONCLUSIONS: Sustained local delivery of PKC412 provides a promising approach for treatment of CNV.

Animals↗
PubMed1994

The applicability of color-labeled microspheres in a rabbit model of ischemia-reperfusion.

This study was designed to examine the ability of color-labeled microspheres to depict different states of myocardial perfusion in a rabbit model of ischemia-reperfusion. A thread was passed under the left anterior descending artery (LAD) and the first left marginal artery of anesthetized New Zealand White rabbits. Blue-labeled microspheres (500/g body wt) were injected into the left atrium. The thread was tightened in rabbits belonging to the experimental group (n = 8), and red-labeled microspheres (500/g body wt) were injected. The snare was loosened, and yellow-labeled microspheres (500/g body wt) were injected before (n = 5) or after (n = 3) methylene blue injection. In animals belonging to the "sham" group (n = 4 and n = 2, respectively), the sequence of injections was similar, but the snare was not tightened. The animals were euthanized, and 0.3-1 g sections were cut from ischemic and nonischemic regions, as determined by methylene blue in the experimental subgroups and from the corresponding regions in the "sham" subgroups. The tissue samples were digested with 4 M KOH, ethanol 70%, and ultrasonication, and the microspheres were recovered by vacuum filtration. The dye was chemically removed from the microspheres, and the photometric absorption of each sample was determined. There was no significant difference between the experimental and "sham" groups in baseline uptake of blue-labeled microspheres. Rabbits belonging to the experimental subgroups had significantly lower mean uptake of red microspheres during ischemia relative to "sham" (0.51 +/- 0.08 vs 1.06 +/- 0.24 and 0.36 +/- 0.19 vs 0.91 +/- 0.12, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Eudragit S100 entrapped insulin microspheres for oral delivery.

The purpose of this research was to investigate whether Eudragit S100 microspheres have the potential to serve as an oral carrier for peptide drugs like insulin. Microspheres were prepared using water-in oil-in water emulsion solvent evaporation technique with polysorbate 20 as a dispersing agent in the internal aqueous phase and polyvinyl alcohol (PVA)/polyvinyl pyrrolidone as a stabilizer in the external aqueous phase. The use of smaller internal aqueous-phase volume (50 microL) and external aqueous-phase volume (25 mL) containing PVA in the manufacturing process resulted in maximum encapsulation efficiency (81.8% +/- 0.9%). PVA-stabilized microspheres having maximum drug encapsulation released 2.5% insulin at pH 1.0 in 2 hours. In phosphate buffer (pH 7.4), microspheres showed an initial burst release of 22% in 1 hour with an additional 28% release in the next 5 hours. The smaller the volumes of internal and external aqueous phase, the lower the initial burst release. The release of drug from microspheres followed Higuchi kinetics. Scanning electron microscopy of PVA-stabilized microspheres demonstrated spherical particles with smooth surface, and laser diffractometry revealed a mean particle size of 32.51 +/- 20 microm. Oral administration of PVA stabilized microspheres in normal albino rabbits (equivalent to 6.6 IU insulin/kg of animal weight) demonstrated a 24% reduction in blood glucose level, with maximum plasma glucose reduction of 76 +/- 3.0% in 2 hours and effect continuing up to 6 hours. The area under the percentage glucose reduction-time curve was 93.75%. Thus, our results indicate that Eudragit S100 microspheres on oral administration can protect insulin from proteolytic degradation in the gastrointestinal tract and produce hypoglycemic effect.

Administration, Oral↗
PubMed2005

Preparation, in vitro release, in vivo absorption and biocompatibility studies of insulin-loaded microspheres in rabbits.

The purpose of this study was to develop a single-dose insulin delivery system based on poly (lactide-co-glycolide) (PLGA) microspheres to provide basal insulin level for a prolonged period. Insulin-loaded PLGA microspheres were prepared by water-in-oil-in-water double emulsion (batch A) and solid-in-oil-in-water emulsion (batch B) methods. Microspheres were characterized for physical characteristics and in vitro release. In vivo absorption of insulin and biocompatibility of insulin-loaded PLGA microspheres were performed in diabetic New Zealand white rabbits. Light and transmission electron microscopy were performed on the skin tissues excised from microspheres injected sites in order to study the biocompatibility. The burst release of insulin was high (47%) from batch B and low (5%) from batch A. Therefore, we mixed microspheres of batch A and B in ratio of 3:1 w/w, which produced desirable in vitro release profile. In vivo absorption study showed that insulin-loaded microspheres provided a serum insulin level of 20-40 microU/ml up to 40 days. Biocompatibility study provided evidence of normal inflammatory and foreign body reactions, which were characterized by the presence of macrophages, fibroblasts and foreign body giant cells. Neither necrosis nor tissue damage was identified. At the end of 12 weeks, no distinct histological differences were observed in comparison to the control tissue samples. In conclusion, insulin-loaded PLGA microspheres controlled the in vivo absorption of insulin to maintain the basal insulin level for longer period and the delivery system was biocompatible.

Animals↗
PubMed2006

Influence of aluminum tristearate and sucrose stearate as the dispersing agents on physical properties and release characteristics of eudragit RS microspheres.

The purpose of this research was to investigate the effects of different concentrations of polymer and sucrose stearate, aluminum tristearate as dispersing agents on microsphere properties and performance. The yield values of microspheres were over the 78%, and the encapsulation efficiencies were found to be approximately 73%. Particle sizes of microspheres prepared with aluminum tristearate were between 76 and 448 microm, while that of the microspheres containing sucrose stearate were between 521 and 2000 microm. Morphological and physicochemical properties of microspheres were investigated by scanning electron micrography and differential scanning calorimetry (DSC). DSC analysis indicated that verapamil hydrochloride formed a solid solution with acrylic polymers. In vitro release studies were performed using the flow-through cell method. While approximately 80% of drug was released from the microspheres containing aluminum tristearate in 480 minutes, the same amount of drug was released from microspheres containing sucrose stearate in only 60 minutes. Chemical structures and concentrations of the dispersing agents were clearly effective on the physical properties of microspheres and their drug-release characteristics.

Acrylic Resins↗
PubMed2002

Study on biodegradable microspheres containing recombinant interferon-alpha-2a.

In this work, a new microsphere delivery system comprising calcium alginate microcores surrounded by a biodegradable poly-DL-lactide-poly(ethylene glycol) (PELA) coat was designed to improve the loading efficiency and stability of peptide drugs. Recombinant interferon (IFN)-alpha-2a, used as a model peptide drug, was efficiently entrapped within the alginate microcores using a high-speed stirrer and then microencapsulated into PELA copolymer using a water-in-oil-in-water solvent extraction method. Microspheres were characterized in terms of morphology, size and distribution, encapsulation efficiency, IFN biological activity retention and in-vitro peptide release. The IFN potency test showed that IFN entrapped in the core-coated microspheres could retain its biological activity during the encapsulation and release procedure. The release profiles were determined by the measurement of peptide presenting in the release medium at various intervals. The IFN potency, calculated by the Wish cells/vesicular stomatitis virus system, was used to determine IFN biological activity. The results showed that the core-coated microspheres could stabilize IFN in the PELA matrix. We compared the new deliverysystem with conventional microsphere delivery systems based on biodegradable poly-DL-lactide and poly-DL-lactide-poly(ethylene glycol). The core-coated microspheres had the highest amount of entrapment, encapsulation efficiency and biological activity retention. The extent of burst release (14%) from the core-coated microspheres in the initial protein release was much lower than the 31% burst release from the conventional microspheres. In conclusion, this work presents a new approach for water-soluble macromolecular drugs delivery (e.g. protein, peptide drugs, vaccines).

Biotechnology↗
PubMed2002

Pharmacokinetic characterization of 14C-vascular endothelial growth factor controlled release microspheres using a rat model.

The objectives of this study were to characterize the pharmacokinetics of vascular endothelial growth factor (VEGF) in poly(lactic-co-glycolic) acid (PLGA) microspheres using a rat model, and to develop a pharmacokinetic model for this controlled release formulation. 14C-VEGF was encapsulated using a solid-in-oil-in-water emulsification method. The microspheres were administered subcutaneously to rats and the pharmacokinetic parameters were compared with those of protein solutions. Intravenous administration of protein solutions resulted in short half-lives and subcutaneous administration resulted in rapid clearance from the subcutaneous tissue, with high plasma concentrations as expressed by rapid absorption and elimination. The subcutaneous administration of the VEGF microspheres produced low plasma concentrations and high subcutaneous concentrations over a period of 7 weeks. The area under the curve (AUC), the time required to achieve the maximum concentration (tmax), the maximum concentration (Cmax) in blood samples and the elimination rate constant (kel) values at the subcutaneous tissue site were selected to compare the pharmacokinetic characterization of VEGF microspheres with that of protein solutions. The in-vivo release profiles of the proteins were slower than the in-vitro release profiles and they followed the same trend as the in-vitro and in-vivo PLGA degradation rates. The PLGA microsphere degradation was the determinant step for VEGF release from the microspheres and its absorption at the subcutaneous site. Microspheres appear to be an attractive system for the localized rate-controlled delivery of VEGF. 14C-Methylation via reductive alkylation of VEGF did not affect its mitogenic activity, however approximately 25% activity was lost following release from PLGA microspheres. This loss of activity may be due to degradation in an acidic environment as a result of PLGA degradation.

Animals↗
PubMed2004

Efficacy of chitosan microspheres for controlled intra-articular delivery of celecoxib in inflamed joints.

The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. In this study, we aimed to prepare celecoxib-loaded chitosan microspheres for intra-articular administration and to compare the retention of the celecoxib solution and chitosan microspheres in the joint cavity. The microspheres were characterized for entrapment efficiency, particle size and surface morphology by scanning electron microscopy. In-vitro drug release studies of microspheres revealed that the microspheres are able to control the release of celecoxib over a period of 96 h. Biodistribution studies of celecoxib and chitosan microspheres were performed by radiolabelling with( 99m)Tc and injecting intraarticularly in rats. The study indicated that following intra-articular administration the distribution of the drug to the organs, like liver and spleen, is very rapid compared with that of the microspheres. Compared with the drug solution, a 10-fold increase in the concentration of the drug in the joint was observed 24 h post intra-articular injection (P < 0.005) when drug was encapsulated in microspheres.

Animals↗
PubMed1993

A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: effects of chitin concentration on cis-diamminedichloroplatinum(II) albumin microsphere properties and antitumor effect in VX2 hepatocellular carcinoma model rabbits.

cis-Diamminedichloroplatinum(II) (CDDP) albumin microspheres were prepared with various chitin concentrations and microsphere CDDP contents, specific surface area, surface structure and other microsphere properties. CDDP release in vitro and the antitumor effect in VX2 tumor model rabbits were investigated. CDDP content was increased as the concentration of chitin increased; at a chitin concentration of 6.0% it was about 2 times that without chitin. Specific surface area also increased with chitin concentration. CDDP release rate from various microspheres in vitro was suppressed as chitin concentration increased. Thus, microsphere properties, especially surface structure, are affected by an increase in chitin concentration. In experiments in vivo, various microspheres were injected into the hepatic artery of VX2 hepatocellular carcinoma model rabbits, and the effects of the chitin concentration on the time course of blood platinum (Pt) level and the antitumor effect were assessed. The blood Pt concentration increased with increase in chitin concentration, with a maximum of 0.45 microgram/ml at a concentration of 6.0%, even 7 d following microsphere administration. Tumor growth was suppressed when the chitin concentration was increased. Tissue Pt concentrations also increased in the presence of chitin. These findings suggest that increasing the chitin concentration might promote microsphere decomposition and hence CDDP release in vivo, thus improving immunopotentiating activity and resulting in enhanced CDDP antitumor effect. The detailed mechanisms of the action, however remains to be studied.

Albumins↗