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 217 records · Page 12Linked to original sources
PubMedDate not supplied

Preparation and characterization of poly(D,L-lactic-co-glycolic Acid) microspheres containing flurbiprofen sodium.

This study aimed to prepare biodegradable microspheres containing flurbiprofen sodium, a nonsteroidal anti-inflammatory drug (NSAID), as the drug delivery system to the periodontal pocket. Microspheres were prepared from biodegradable copolymers of poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation method. The effects of the different copolymers and amounts of polyvinyl alcohol (PVA) as a dispersing agent on characteristics of the microspheres were evaluated. Although there was no correlation between microsphere size and amount of PVA, an optimum PVA concentration was essential to achieve narrower size distributions of microspheres. As the concentration of PVA increased, the drug loading of the microspheres increased. The effect of PVA on drug loading was found to be statistically significant for those microspheres prepared from PLGA 50:50 (p < 0.05). Regarding copolymer composition, PLGA 85:15 provided higher drug loading into the microspheres than PLGA 50:50 (p < 0.05). The recoveries of microspheres (60-80%) were affected neither by different PVA concentrations nor by copolymer compositions (p > 0.05). According to the first-order release rate constants of the microspheres, the microspheres of PLGA 50:50 released the drug at the highest rate consistently, with the highest hydrophilicity of this copolymer.

Algorithms↗
PubMed2004

Aqueous preparation and evaluation of albumin-chitosan microspheres containing indomethacin.

Controlled-release egg albumin-chitosan microspheres containing indomethacin as a model drug were successfully prepared by coacervation method. The proposed method can offer a simple method for microsphere preparation in an aqueous system with the elimination of the use of organic solvents that are usually needed in conventional techniques of microencapsulation. The interaction between negatively charged egg albumin molecules in phosphate buffer, pH 7.2, or sodium hydroxide solution and positively charged chitosan molecules dissolved in diluted acetic acid to form an insoluble precipitate was the principle for the formation of the microspheres. The effects of many process variables, such as amount of formaldehyde as a cross-linking agent, stirring time, final pH of encapsulation medium, initial drug loading, and albumin concentration or albumin-to-chitosan weight ratio, on the properties of the prepared microspheres were investigated. Incorporation efficiencies of the microspheres to the drug were high in most cases and ranged between 63.3 +/- 3.6% and 92.39 +/- 3.2%, while particle sizes were 435.2 +/- 12.6 up to 693.9 +/- 34.6 microm for the different tested batches. On the other hand, the values of angles of repose and compressibility indices were in the range of 23.5 +/- 0.4 to 32.0 +/- 0.7 degrees and 11.1 +/- 0.7% to 23.6 +/- 0.7% respectively, which indicate overall good free flowing nature of the microspheres of all batches. The maximum required amount of the cross-linking agent was determined to avoid excessive unnecessary chemicals. It was also noticed that excessive time of stirring and excessive initial drug loading are not recommended as it may lead to microspheres of low properties. The pH of the encapsulation media (pH 3.77 up to pH 4.91) significantly affected the properties of the microspheres. As the pH of the encapsulation media was increased, the incorporation efficiency, particle size, and flowability decreased, along with increase of drug release rate, which could be related to incomplete cross linking of the microspheres matrix. It was also observed that high concentration of albumin solution and accordingly the increase of albumin-to-chitosan weight ratio were accompanied with increases in incorporation efficiency and particle size with improved microsphere flowability and slow indomethacin release. Thus, the proposed microspheres showed the ability to control the release of indomethacin, and their properties were highly affected by many process variables that could be controlled to obtain an optimized system.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Stomach-specific anti-H. pylori therapy. II. Gastric residence studies of tetracycline-loaded chitosan microspheres in gerbils.

This study examines the gastric residence of chitosan microspheres and the local tetracycline concentrations following oral administration in gerbils. Chitosan microspheres were prepared by ionic cross-linking and precipitation with sodium sulfate. Gastric retention studies were performed by administering radioiodinated [125I] chitosan microsphere suspension in the nonacid-suppressed and acid-suppressed states. At different time points, animals were sacrificed, and the radioactivity in tissues and fluids was measured with a gamma counter. Local tetracycline concentrations were measured using chitosan microspheres loaded with tritiated-[3H]-tetracycline. The radioactivity, measured with a liquid scintillation analyzer, was used to determine the microg of drug per gram of tissues or fluids under nonacid-suppressed and acid-suppressed states. Microspheres with a spherical shape and an average diameter of 2.0-3.0 microm were formed. After 2 hr in the fasted stomach, approximately 10% of the administered dose remained. The microspheres were predominantly found in the colon after 6 hr of administration. There was no detectable radioactivity in the small intestine, plasma, urine, liver, and kidneys. Additionally, acid suppression with ranitidine did not influence the gastric residence time of chitosan microspheres. To our disappointment, tetracycline concentration profile in the stomach from microsphere formulation was similar to the aqueous solution. Also, there was no significant difference between the stomach tetracycline concentrations in the nonacid-suppressed and acid-suppressed states. The drug was predominantly found in the colon and urine samples after 6 hr. Tetracycline could not be detected in the plasma, small intestine, liver, or kidneys. Results of this study show that chitosan microspheres prepared by ionic cross-linking do not provide a longer residence time in the fasted gerbil stomach. The tetracycline concentration profile in the stomach, following administration in microsphere formulation, was similar to that of aqueous solution. Lastly, acid suppression did not influence the gastric residence time of chitosan microspheres or tetracycline concentration profiles.

Animals↗
PubMed1994

Developments in non-radioactive microsphere techniques for blood flow measurement.

Considerable progress is being made in the development of non-radioactive microsphere methods. Validation studies of the three commercially available non-radioactive microspheres are promising. In most experimental conditions the use of non-radioactive microspheres saves money. Avoiding the use of radioactivity facilitates the use of microspheres in chronic animal experiments and when blood flow and chemical measurements are performed in the same sample. Moreover, using histological techniques, distributions of coloured or fluorescent microspheres in subunits of organs could be quantified, opening new scientific possibilities. Currently, the fluorescent microsphere technique seems to be the most promising non-radioactive microsphere method. Due to the high sensitivity and good spectral separation, the number of microspheres injected can be as small as that used, for radioactive microspheres, at least six labels can be used, and the relatively large volume in which fluorescence is measured (approximately 1-3 ml) enables the use of time saving microsphere isolation techniques. Development of these methods and further automation of the quantification process (using either automised spectrometry or FACS analysis) will considerably increase interest in the non-radioactive microsphere techniques. To accelerate these developments, investigators are encouraged to share their experiences.

Animals↗
PubMed1998

Intramural injection of biodegradable microspheres as a local drug-delivery system to inhibit neointimal thickening in a rabbit model of balloon angioplasty.

Restenosis remains the major limitation of coronary angioplasty. The objective of this study was to develop microspheres able to be delivered at the angioplasty site for long-term drug release and to test their effects in a model of balloon angioplasty. Polylactic-co-glycolide acid microspheres (5-10 microm in diameter) were prepared by using an oil-in-water emulsion-solvent evaporation method. In vitro experiments with hydrocortisone-loaded microspheres revealed a hydrocortisone release for 4 weeks. We studied the in vivo effect of injection of microspheres into the arterial wall of New Zealand White rabbits by using a perforated balloon. Deep penetration of microspheres in the arterial wall was documented immediately after angioplasty. Intimal hyperplasia was assessed in iliac arteries 4 weeks after angioplasty. The morphometric analysis was performed in four groups of animals; the first group was subjected only to conventional angioplasty (control, n = 10), whereas the other three groups after conventional angioplasty were received perforated balloon angioplasty with saline (n = 10), microspheres (n = 10), or hydrocortisone-loaded microspheres (n = 7). Intramural injection of saline did not induce greater intimal hyperplasia compared with control (0.17 +/- 0.03 vs. 0.18 +/- 0.03 mm2, respectively). Microspheres injection was associated with a trend toward a greater degree of intimal hyperplasia that did not reach statistical significance. Hydrocortisone-loaded microspheres were associated with a significant reduction in intimal hyperplasia compared with unloaded microspheres (0.16 +/- 0.02 vs. 0.26 +/- 0.03 mm2, respectively). The polylactic-co-glycolide acid microspheres are well tolerated, easily injected into the arterial wall, and the increase of intimal hyperplasia is easily inhibited by release of hydrocortisone for 4 weeks after initial injury.

Angioplasty, Balloon↗
PubMed2000

De novo adipose tissue generation through long-term, local delivery of insulin and insulin-like growth factor-1 by PLGA/PEG microspheres in an in vivo rat model: a novel concept and capability.

This study was undertaken to characterize the duration of long-term growth factor delivery by poly(lactic-co-glycolic-acid)-polyethylene glycol (PLGA/PEG) microspheres and to evaluate the potential of long-term delivery of insulin and insulin-like growth factor-1 (IGF-1) for the de novo generation of adipose tissue in vivo. PLGA/PEG microspheres containing insulin and IGF-1, separately, were produced by a double-emulsion solvent-extraction technique. In the first phase of the experiment, the in vitro release kinetics of the microspheres were evaluated for the optical density and polyacrylamide gel electrophoresis of solutions incubated with insulin-containing microspheres for four different periods of time (n = 1). The finding of increased concentrations of soluble insulin with increased incubation time confirmed continual protein release. In the second stage of the experiment, 16 rats were divided equally into four study groups (insulin, IGF-1, insulin + IGF-1, and blank microspheres) (n = 4). Insulin and IGF-1 containing microspheres were administered directly to the deep muscular fascia of the rat abdominal wall to evaluate the potential for de novo adipose tissue generation via adipogenic differentiation from native nonadipocyte cell pools in vivo. Animals treated with blank microspheres served as an external control group. At the 4-week harvest period, multiple ectopic islands of adipose tissue were observed on the abdominal wall of the animals treated with insulin, IGF-1, and insulin + IGF-1 microspheres. Such islands were not seen in the blank microsphere group. Hematoxylin and eosin-stained sections of the growth factor groups demonstrated mature adipocytes interspersed with fibrous tissue superficial to the abdominal wall musculature and continuous with the fascia. Oil-Red-O stained sections demonstrated that these cells contained lipid. Computer-aided image analysis of histologic sections confirmed that there were statistically significant increases in the amount of "ectopic" adipose neotissue developed on the abdominal wall of animals treated with growth factor microspheres. In conclusion, this study confirms the long-term release of proteins from PLGA/PEG microspheres up to 4 weeks and demonstrates the potential of long-term local insulin and IGF-1 to induce adipogenic differentiation to mature lipid-containing adipocytes from nonadipocyte cell pools in vivo at 4 weeks.

Abdominal Muscles↗
PubMed2004

Microspheres accurately predict regional bone blood flow.

Even though the microsphere method frequently is used to determinate bone blood flow, validation of this technique for bone blood flow measurement is incomplete. The method is based on the principle that injected microspheres are distributed with the arterial blood and trapped in the capillaries because of their diameter (15 microm). The number of spheres lodged in an organ is proportional to its blood flow. The number of radioactive or fluorescent microspheres in a specific organ is determined indirectly by measuring radioactivity or fluorescence intensity in the organ. In this study the reliability and precision of the microsphere method for determining bone blood flow was established using radioactive and fluorescent microspheres. Six female, anesthetized New Zealand rabbits received left ventricular injections of pairs of fluorescent and/or radioactive microspheres. The humerus, femur, and tibia were dissected in a standardized manner and blood flow was determined in each sample. Comparison of relative blood flow values showed an excellent correlation between radioactive and fluorescent microspheres. The percentage difference and variation between two simultaneously injected sets of microspheres was minimal for radioactive microspheres (0.8% +/- 9.6%) and for fluorescent microspheres (0.2% +/- 11.4%). Regional bone blood flow in different regions of the femur, tibia, or humerus ranged from 2.2-28.1 mL/minute/100 g, but there was no significant difference between right and left bone samples of the same region after repeated measurement. Radioactive and fluorescent microspheres allow precise determination of regional bone blood flow.

Animals↗
PubMed2003

In vitro study of the compatibility of tris-acryl gelatin microspheres with various chemotherapeutic agents.

PURPOSE: To evaluate the in-vitro effects of chemotherapeutic agents on the physical structure of tris-acryl gelatin microspheres. MATERIALS AND METHODS: Microspheres (Embospheres) were mixed in vitro with carboplatin, mitomycin C, 5-fluorouracil, or pirarubicin as experimental samples and with distilled water as control samples and kept for 24 hours at 37 degrees C. The microspheres used measured 100-300 micro m and 700-900 micro m in diameter. Microsphere morphology, including appearance, overall shape, smoothness of surface, and thickness of gelatin coating, was examined with use of a microscope equipped with a cold light. Microsphere dimensions including larger diameter, smaller diameter, and surface area were measured by granulometry. Microsphere geometry was evaluated by calculating a sphericity index and surface regularity index. Qualitative and quantitative variables, respectively, were analyzed with the two-sided Fisher exact test and Wilcoxon signed-rank test for paired values, with a significance level of 0.05. RESULTS: No broken microspheres or microscopic degradations in the appearance, overall shape, smoothness of surface, or thickness of gelatin coating of any microspheres were observed. The respective distributions of large and small diameters, surface area, sphericity index, or surface regularity index of the microspheres were not significantly different between the experimental samples containing carboplatin, mitomycin C, 5-fluorouracil, or pirarubicin and the control sample of microspheres with similar diameters. CONCLUSION: Embosphere microspheres can be mixed with carboplatin, mitomycin C, 5-fluorouracil, or pirarubicin for chemoembolization therapy without any risk of damaging their morphology, dimensions, or geometric characteristics.

Acrylates↗
PubMed1978

The effect of ergotamine on tissue blood flow and the arteriovenous shunting of radioactive microspheres in the head.

1 The radioactive microsphere method was used to study the effects of ergotamine (5, 10 and 20 mug/kg, i.v.) on systemic and regional haemodynamic variables in chloralose-urethane anaesthetized cats. The influence of the drug was also studied on the number of 15 mum microspheres escaping entrapment in the head to emerge in the left external jugular vein.2 Ergotamine decreased the heart rate and cardiac output. Since arterial blood pressure remained unchanged, calculated total peripheral resistance increased.3 The regional distribution of cardiac output obtained with 15 mum microspheres agreed well with previous studies in cats where 25 mum spheres were used. The most pronounced difference was that in the present investigation more microspheres, apparently escaping through arteriovenous anastomoses (AVAs), were detected in the lungs than when larger spheres had been used.4 Coronary blood flow decreased, while uterine blood flow was increased by the drug. The microsphere content of the lungs, which receive the spheres not only via bronchial arteries but also via AVAs, was greatly reduced by all doses of ergotamine. Ergotamine did not influence tissue blood flow to other major organs such as the brain, kidneys, skin, liver, skeletal muscle or the gastrointestinal tract.5 In the 16 experiments, 0.46 +/- 0.05 (s.e. mean)% of the total microspheres injected (equivalent to 11.7 +/- 1.4% of microspheres detected in the left-side of the head) appeared within 2 min of microsphere injection into the left external jugular vein. The highest dose of ergotamine significantly reduced the shunting of the microspheres in the head.6 Since 15 mum microspheres are only likely to reach the lungs by passing into the venous circulation through large glomus-type AVAs, we conclude that ergotamine reduces the fraction of microspheres appearing in the lungs by causing strong vasoconstriction in the AVAs in the head.7 In conformity with the closure of head AVAs is the finding that ergotamine reduced the jugular venous Po(2) and O(2) saturation thereby increasing the A-V O(2) saturation difference.8 It is quite possible that decreased A-V shunting may be the prominent mechanism of the antimigraine action of the drug, since sudden opening of AVA's has been implicated in the pathophysiology of migraine-syndrome.

Animals↗
PubMed2002

Bioactive, degradable composite microspheres: effect of filler material on surface reactivity.

Composite microspheres with two different fillers were developed using a solid-in-oil-in-water (s/o/w) emulsion solvent removal method. Two types of bioactive ceramic powders, specifically calcium hydroxyapatite (HA) and modified bioactive glass (MBG), were incorporated into degradable poly(lactic acid) (PLA) polymer matrix to form composite microspheres. For each filler material, microspheres with three different weight ratios of filler material to polymer, namely, 1: 1, 1: 3, and 1: 9, were synthesized. In vitro immersion using simulated physiological fluid (SPF) was employed to evaluate the surface reactivity of the microspheres. SEM analysis revealed that after a 14-day immersion the surface of the microspheres containing 50% MBG was fully transformed into a bone-like apatite. In contrast, a limited number of mineral nodules were present on the surface of microspheres containing HA. The solution chemical analyses performed to determine changes of Ca, P, and Si concentrations as a function of the immersion time showed that the ion concentration profiles were similar for all microspheres, except the [Si] profile. A higher Si concentration was detected in the SPF immersed with MBG-containing microspheres. These data show that the MBG filler significantly enhances the surface reactivity of the composite microspheres. This observation enables us to conclude that the composite MBG-containing microspheres are the preferable microspheres for three-dimensional bone tissue engineering.

Biocompatible Materials↗
PubMed1984

Validation of quantitation of regional myocardial blood flow in vivo with 11C-labeled human albumin microspheres and positron emission tomography.

Use of radiolabeled microspheres is a standard method to measure regional myocardial perfusion in animals. Human albumin microspheres have been given safely to patients, but positron-emitting 68Ga-labeled human albumin microspheres are characterized by an unstable radiolabel. A new labeling procedure that covalently binds 11C (t1/2 = 20.3 min) to human albumin microspheres via 11CH3I was developed. Seven open-chest and two closed-chest dogs were studied. Reference and 11C-labeled human albumin microspheres (2 to 25 mCi) were both injected into the left atrium. Positron tomographic images were obtained of the myocardial distribution of the 11C-labeled microspheres. Timed arterial withdrawal was used for both reference gamma-labeled microspheres and 11C-labeled human albumin microspheres. Myocardial tissue samples matched to tomographic slices were well-counted for calculation of reference values of regional myocardial perfusion. Serial venous blood samples for residual 11C activity of 30 and 60 min after injection were less than 1% of the myocardial 11C concentration demonstrating a stable 11C bond to the human albumin microspheres. Regional myocardial perfusion calculated by this technique correlated well with values obtained with reference microspheres (r = .97) over a range of 0.2 to 3.5 ml/min/g. Correction for wall thickness improved the slope of the regression equation from y = 0.71 x -0.03 to y = 0.88 X -0.05. Thus, 11C human albumin microspheres are stable radiochemically and can be used as a quantitative measure of regional myocardial perfusion.

Animals↗
PubMed1994

Arterial microsphere concentrations in cats are not affected by changes in hematocrit.

BACKGROUND AND PURPOSE: Acute anemia may lead to erroneously low arterial reference sample concentrations of radioactive microspheres, depending on the sampling rate and the size of the artery from which the reference samples are withdrawn. Because this error would lead to falsely high cerebral blood flow values in studies involving hemodilution caused by hemorrhage and fluid resuscitation, we studied the effects of hematocrit, withdrawal rate, and vessel location and size on arterial microsphere concentrations in anesthetized adult cats. METHODS: Cats were anesthetized with ketamine, isoflurane, and nitrous oxide; both brachial arteries were cannulated with polyethylene tubing, as was the abdominal aorta through the femoral artery. Sequential left atrial microsphere injections were made using several doses of each of five isotopes. The rate of reference sample withdrawal from the three sampling catheters was randomized to 1.03 mL.min-1 or 2.06 mL.min-1. We analyzed the ratio of the number of microspheres in paired reference samples using the factors hematocrit, rate of withdrawal, and site. A ratio less than 1 indicates an underestimation of arterial microsphere concentration, which would lead to erroneously high cerebral blood flow values. The procedure was repeated after isovolemic hemodilution with 10% hetastarch to hemoglobin levels approximating 85%, 70%, 55%, and 40% of baseline. RESULTS: No significant effects of hematocrit on ratios of microsphere concentrations existed at any withdrawal rate or site. Ratios of microsphere concentrations in reference samples withdrawn slowly (1.03 mL.min-1) from the aorta and ratios of microsphere concentrations withdrawn either rapidly (2.06 mL.min-1) or slowly from the brachial arteries were significantly (P < .001) less than 1. CONCLUSIONS: Hemodilution did not affect microsphere concentrations in arterial reference samples at any withdrawal site or rate and therefore does not affect the accuracy of microsphere blood flow determinations. However, slow withdrawal from a large vessel may underestimate actual microsphere concentrations.

Animals↗
PubMed2004

Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods.

The mucoadhesive properties of chitosan microspheres prepared by different methods were evaluated by studying the interaction between mucin and microspheres in aqueous solution. The interaction was determined by the measurement of mucin adsorbed on the microspheres. A strong interaction between chitosan microspheres and mucin was detected. The intensity of the interaction was dependent upon the method of preparation of chitosan microspheres and the amount of mucin added. The extent of mucus adsorption was proportional to the absolute values of the positive zeta potential of chitosan microspheres. The zeta potential in turn was found to be dependent upon the method of preparation of microspheres. The adsorption of type III mucin (1% sialic acid content) was interpreted using Freundlich or Langmuir adsorption isotherms. The values of r2 were greater for Langmuir isotherm as compared with Freundlich isotherm. The adsorption of a suspension of chitosan microspheres in the rat small intestine indicated that chitosan microspheres prepared by tripolyphosphate cross-linking and emulsification ionotropic gelation can be used as an excellent mucoadhesive delivery system. The microspheres prepared by glutaraldehyde and thermal cross-linking showed good stability in HCl as compared with microspheres prepared by tripolyphosphate and emulsification ionotropic gelation.

Animals↗
PubMed2006

Spray-dried mucoadhesive microspheres: preparation and transport through nasal cell monolayer.

The purpose of this research was to prepare spray-dried mucoadhesive microspheres for nasal delivery. Microspheres composed of hydroxypropyl methylcellulose (H), chitosan (CS), carbopol 934P (CP) and various combinations of these mucoadhesive polymers, and maltodextrin (M), colloidal silicon dioxide (A), and propylene glycol (P) as filler and shaper, were prepared by spray-drying technique. Using propranolol HCl as a model drug, microspheres were prepared at loadings exceeding 80% and yields between 24% and 74%. Bulky, free flowing microspheres that had median particle size between 15 and 23 mum were obtained. Their zeta potential was according to the charge of polymer. Adhesion time of mucoadhesive microspheres on isolated pig intestine was ranked, CS > CP:H > CP > H, while the rank order of swelling was CP > CS > H. Increasing the amount of CP in CP:H formulations increased the percentage of swelling. Infrared (IR) spectra showed no interaction between excipients used except CS with acetic acid. The release of drug from CP and CP:H microspheres was slower than the release from H and CS microspheres, correlated to their viscosity and swelling. Long lag time from the CP microspheres could be shortened when combined with H. The permeation of drug through nasal cell monolayer corresponded to their release profiles. These microspheres affected the integrity of tight junctions, relative to their swelling and charge of polymer. Cell viability was not affected except from CS microspheres, but recovery could be obtained. In conclusion, spray-dried microspheres of H, CS, CP, and CP:H could be prepared to deliver drug through nasal cell monolayer via the opening of tight junction without cell damaging.

Acrylates↗
PubMed2006

An investigation into the adjuvanticity and immunogenicity of zein microspheres being researched as drug and vaccine carriers.

We have determined whether zein microspheres could act as vaccine adjuvants i.e. increase the immune responses to co-administered immunogens. Ovalbumin (model antigen)-loaded zein microspheres, blank zein microspheres and ovalbumin solution were intramuscularly administered to mice and the sera antibody levels were determined by ELISA. Another group of mice was orally dosed with blank zein microspheres, and serum and faecal antibody levels were determined. As expected, negligible antibody titres were obtained with the ovalbumin solution. Surprisingly, intramuscular administrations of blank zein microspheres elicited high levels of serum IgG which bound to the ovalbumin antigen coated on ELISA microtitre plates. This indicated that anti-zein antibodies had been elicited by blank zein microspheres and that these antibodies were cross-reacting with ovalbumin antigen coated onto ELISA plates. Such cross-reactivity inhibited the determination of the adjuvant activity of zein microspheres, if any. Additional ELISA assays, where zein was used as the coating antigen, confirmed the generation of anti-zein antibodies by blank zein microspheres i.e. zein microspheres were immunogenic following intramuscular administration. Upon oral administration of blank zein microspheres, serum IgG levels remained low but intestinal IgA levels increased following booster doses i.e. systemic tolerance, but not mucosal tolerance, to oral zein particles was achieved. Zein microspheres were immunogenic when administered intramuscularly and orally.

Administration, Oral↗
PubMed2005

Chitosan-based mucoadhesive microspheres of clarithromycin as a delivery system for antibiotic to stomach.

The objective of the present study was to develop chitosan-based mucoadhesive microspheres of clarithromycin to provide prolonged contact time for drug delivery of antibiotics to treat stomach ulcers. Microspheres based mucoadhesive formulation were extensively evaluated and characterized for in vitro performance followed by investigation of in vivo pharmacokinetics in rats. Microspheres were prepared by emulsification technique using glutaraldehyde as a crosslinking agent. Formulation conditions were optimized for percent drug entrapment and mucoadhesion, by varying different formulation and process parameters like drug to polymer ratio, concentration of crosslinking agent and time of crosslinking. Prepared microspheres were evaluated extensively for particle size, percent drug entrapment, swelling kinetics, in vitro mucoadhesion using rat stomach membrane and in vitro drug release studies. In vitro permeation studies across rat stomach membrane were carried out to determine diffusion parameters and drug retention in the stomach membrane of the formulation and the plain drug. Finally in vivo performance of microsphere formulation in comparison to plain drug was evaluated by pharmacokinetic studies in albino rats. Drug entrapment upto 74% was obtained. Swelling studies indicated that with an increase in cross-linking, the swelling ability decreased. The in vitro drug release and in vitro mucoadhesion studies showed a dependence on the extent of cross-linking and concentration of chitosan. Extent of cross-linking exhibited an inverse relation to drug release rate as well as mucoadhesion, whereas polymer concentration exhibited an inverse correlation with drug release while linear relationship with mucoadhesion (up to 86%). In vitro permeation studies across stomach tissue showed higher accumulation of drug in the stomach tissue with microspheres formulation as compared to that of free drug. This is evident from higher value of K (partition coefficient) and Qm/Csf values for microspheres (68.34 and 106.42X10(3), respectively) as compared to that of free drug (1.86 and 173.00, respectively). These findings when analyzed showed an increase in the bioavailability of clarithromycin from microsphere formulation as compared to plain drug suspension in vivo, with AUC 0-->alpha being 91.7 (microg h/ml)and 24.9 (microg h/ml) respectively. Results of the study demonstrated good mucoadhesion of the microspheres with the stomach mucosa as well as higher accumulation of drug in the stomach membrane. Microspheres also exhibited sustained release of drug. Thus chitosan microspheres appear, technically, promising mucoadhesive drug delivery systems for delivering clarithromycin to treat stomach ulcers.

Animals↗
PubMed1994

In vitro phagocytosis of polylactide microspheres by retinal pigment epithelial cells and intracellular drug release.

We investigated phagocytosis of biodegradable microspheres containing a drug by retinal pigment epithelial (RPE) cells and drug release within the cells to evaluate the potential usefulness of microspheres for intracellular drug delivery. The biodegradable polymers used were L-lactic acid, and DL-lactic acid with different molecular weights or the copolymers of different monomer compositions. The microspheres containing a non-bioactive fluorescent dye (rhodamine 6GX) as a model drug, were prepared by a solvent evaporation method. The in vitro release of the dye from the microspheres was examined. Phagocytosis of the microspheres by RPE cells was conducted to evaluate the extent of phagocytosis by phase-contrast microscopy and transmission electron microscopy. The RPE cells ingesting the microspheres at different stages were examined by fluorescent microscopy to estimate the intracellular release of the dye. The dye was released with time from every microsphere and the release was controlled by changing the type of polymers constituting microspheres. The microspheres containing the dye were phagocytosed by RPE cells and the dye was released intracellularly with time. The present study indicates that the drug incorporated in the microspheres was delivered into RPE cells by way of phagocytosis and released within the cells. It is concluded that this microsphere system is a promising delivery form capable of drug targeting to RPE cells.

Animals↗
PubMedDate not supplied

Preparation and release characteristics of polymer-coated and blended alginate microspheres.

To prevent a rapid drug release from alginate microspheres in simulated intestinal media, alginate microspheres were coated or blended with polymers. Three polymers were selected and evaluated such as HPMC, Eudragit RS 30D and chitosan, as both coating materials and additive polymers for controlling the drug release. This study focused on the release characteristics of polymer-coated and blended alginate microspheres, varying the type of polymer and its concentration. The alginate microspheres were prepared by dropping the mixture of drug and sodium alginate into CaCl(2) solution using a spray-gun. Polymer-coated microspheres were prepared by adding alginate microspheres into polymer solution with mild stirring. Polymer-blended microspheres were prepared by dropping the mixture of drug, sodium alginate and additive polymer with plasticizer into CaCl(2) solution. In vitro release test was carried out to investigate the release profiles in 500 ml of phosphate buffered saline (PBS, pH 7.4). As the amount of polymer in sodium alginate or coating solution increase, the drug release generally decreased. HPMC-blended microspheres swelled but withstood the disintegration, showing an ideal linear release profiles. Chitosan-coated microspheres showed smooth and round surface and extended the release of drug. In comparison with chitosan-coated microspheres, HPMC-blended alginate microspheres can be easily made and used for controlled drug delivery systems due to convenient process and controlled drug release.

Acrylic Resins↗