• Archives of Pharmacal Research
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• v.28 no.5
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• pp.612-618
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• 2005

A mucoadhesive microsphere was prepared by an interpolymer complexation and solvent evaporation method, using chitosan and poly(acrylic acid) (PAA), to prolong the gastric resid ence time of the delivery system. The Fourier transform infrared results showed that microspheres were formed by an electrostatic interaction between the carboxyl groups of the PAA and the amine groups of the chitosan. X-ray diffraction and differential scanning calorimetry analysis showed that the enrofloxacin in the chitosan-PAA microsphere was molecularly dispersed in an amorphous state. Scanning electron microscopy of the surface and the quantity of mucin attached to the microspheres indicated that chitosan-PAA microspheres had a higher affinity for mucin than those of chitosan alone. The swelling and dissolution of the chitosan-PAA microspheres were found to be dependent on the pH of the medium. The rate of enrofloxacin released from the chitosan-PAA microspheres was slower at higher pH; therefore, based on their mucoadhesive properties and morphology, the chitosan-PAA microspheres can be used as a mucoadhesive oral drug delivery system.

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.346-350
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• 2004

Chitosan microspheres were prepared by ionic gelation process with sodium sulfate for nasal vaccine delivery. Bordetella Bronchiseptica Dermonecrotoxin (BBD) as a major virulence factor of a causative agent of atrophic rhinitis (AR) was loaded to the chitosan microspheres for vaccination. Morphology of BBD-loaded chitosan microspheres was observed as spherical shapes. The average particle sizes of the BBD-loaded chitosan microspheres were about $2.69$\mid${\;}\mu\textrm{m}$. More BBD was released with an increase of molecular weight of chitosan and with an increase of medium pH in vitro due to weaker intermolecular interaction between chitosan and BBD. Tumor necrosis $factor-{\alpha}{\;}(TNF{\alpha})$ and nitric oxide (NO) from RAW264.7 cells stimulated with BBD-loaded chitosan microspheres were gradually secreted, suggesting that released BBD from chitosan microspheres had immune stimulating activity of AR vaccine.

• Journal of Pharmaceutical Investigation
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• v.35 no.2
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• pp.95-99
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• 2005

Mucoadhesive microspheres were prepared by interpolymer complexation of chitosan with poly(acrylic acid) (PAA) and solvent evaporation method to increase gastric residence time. The chitosan-PAA complex formation was confirmed by differential scanning calorimetry and swelling study. The DSC thermogram of chitosan-PAA microspheres showed two exothermic peaks for the decomposition of chitosan and PAA. The swelling ratio of the chitosan-PAA microspheres was dependent on the pH of the medium. The swelling ratio was higher at pH 2.0 than at neutral pH. The results indicated that the microspheres were formed by electrostatic interaction between the carboxyl groups of PAA and the amine groups of chitosan. The effect of various process parameters on the formation and morphology of microspheres was investigated. The best microspheres were obtained when 1.5% of the high molecular weight chitosan and 0.3% of PAA were used as an internal phase. The optimum internal phase volume was 7%. The com oil was used as the external phase of emulsion, and span 80 was used as the surfactant. The prepared microspheres had spherical shape.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.570-573
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• 2005

The spray method was chiefly used to prepare alginate microspheres. Additionally due to formation at mild conditions, the alginate microspheres were coated with chitosan. The particle size of alginate microspheres increased when the sodium alginate increased. Release pattern of OVA in alginate microspheres was evaluated at PBS buffer(pH 7.4) and HCl buffer(pH 1.2). Release rate of OVA from chitosan/alginate microsphere was also lower than that with the concentration of alginate in the microspheres, the amount of OVA released from alginate microspheres increased from alginate micorsphere. Therefore, the alginate microspheres can be prepared by spray rozzle for a protein drug delivery. OVA release from the alginate microspheres was controlled by a coating with chitosan.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.185-190
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• 2011

The purpose of this study was to evaluate the phagocytic uptake of surface modified PLGA microspheres containing ovalbumin (OVA) into dendritic cell. In order to find the most suitable formulation for targeted delivery to antigen presenting cells (APC), OVA was encapsulated by a double emulsion solvent evaporation method with three PLGA microspheres (PLGA 50:50, PLGA 75:25 and PLGA 85:15) and two surface modified microspheres by chitosan and sodium dodecyl sulfate (SDS). Physicochemical properties were evaluated in terms of size, zeta potential, encapsulation efficiency, different scanning calorimeter (DSC), x-ray diffraction, morphology, and OVA release test from microspheres. Phagocytic activity was estimated using dendritic cells and analyzed by fluorescence activated cell sorter (FACS). The result showed that zeta potential of PLGA particles was changed to positive by the chitosan modification. The release profile of chitosan modified PLGA microspheres exhibited sustained release after initial burst. The chitosan modified microspheres had higher phagocytic uptake than the other microspheres. Such physicochemical properties and phagocytic uptake studies lead us to conclude that chitosan modified microspheres is more suitable formulation for the targeted delivery of antigens to APC compared with the other microspheres.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.98-103
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• 2009

Superparamagnetic iron oxide nanoparticles (SPIOs)-embedded chitosan microspheres were developed for magnetic resonance (MR)-traceable embolotherapy. SPIOs-loaded chitosan microspheres were prepared by emulsion and cross-linking technique and 100-200 ${\mu}m$ sized spherical microsparticles were obtained. Loading efficacy and loading amount of SPIOs in microspheres were about 40% and 0.26-0.32%, respectively, when measured by inductively coupled plasma atomic emission spectroscopy. Within 30 days, about 60% of the incorporated SPIOs were released from low cross-linked microspheres, whereas only about 40% of SPIOs was released from highly cross-linked microspheres. Highly cross-linked microspheres were more efficient for lower degree of swelling leading to secure entrapment of SPIOs in matrix. Prepared novel embolic microspheres are expected to be practically applicable for traceable embolotherapy with high resolution and sensitivity through magnetic resonance imaging (MRI).

• Journal of the Korean Chemical Society
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• v.57 no.4
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• pp.439-446
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• 2013

Chitosan (CS) and hydroxypropylmethyl cellulose (HPMC) blend microspheres were prepared by water-in-oil emulsion technique and were loaded with an anti-cancer drug 5-fluorouracil (5-FU). CS-HPMC microspheres were characterized by Fourier transform infrared spectroscopy to confirm the cross-linking reaction. Scanning electron microscopy (SEM) was also used to assess the surface morphology of particles prepared. The quantity of release of 5-FU from the microspheres have been studied in terms of blend composition and amount of cross-linking agent. Differential scanning calorimetry and X-ray diffraction techniques indicated a uniform distribution of 5-FU particles in microspheres, whereas SEM suggested the spherical structure of the microspheres with slight rough surface. The in vitro drug release indicated that the particle size and release kinetics depend upon blend composition, amount of cross-linking agent used and amount of 5-FU present in the microspheres.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.241-256
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• 2001

Alginate microspheres, containing fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) or green fluorescent protein (GFP) were prepared and used as a model drug to develop the oral vaccine delivery system. The alginate microspheres were coated with poly-L-lysine or chitosan. Two methods, w/o-emulsion and spray, were used to prepare alginate microspheres. To optimize preparation conditions, effects of several factors on the particle size and particle morphology of microsphere, and loading efficiency of model antigen were investigated. In both preparation methods, the particle size and the loading efficiency were enhanced when the concentration of sodium alginate increased. In the w/o-emulsion preparation method, as the concentration of Span 80 was increased from 0.5% to 2%, the particle size was decreased, but the loading efficiency was increased. The higher the emulsification speed was, the smaller the particle size and loading efficiency were. The concentration of calcium chloride did not show any effect on the particle size and loading efficiency. In the spray preparation method, the particle size was increased as the nozzle pressure $(from\;1\;kgf/m^2\;to\;3\;kgf/m^2)$ and spray rate was raised. Increasing calcium chloride concentration (<7%) decreased the particle size, in contrast to no effect of calcium chloride concentration on the w/o-emulsion preparation method. Alginate microspheres prepared by two methods were different in the particle size and loading efficiency, the particle size of microspheres prepared by the spray method was about $2-6\;{\mu}m$, larger than that prepared by the w/o emulsion method $(about\;2{\mu}m)$, and the loading efficiency was also higher with spray method. Furthermore, drying process for the microspheres prepared by the spray was simpler and easier, compared with the w/o emulsion preparation. Therefore, the spray method was chosen to prepare alginate microspheres for further experiments. Release pattern of FITC-BSA in alginate microspheres was evaluated in simulated intestinal fluid and PBS (phosphate buffered saline). Dissolution rate of FITC-BSA from alginate/chitosan microsphere was lower than that from alginate microsphere and alginate/poly-L-lysine microsphere. By confocal laser scanning microscope, it was revealed that alginate/FITC-poly-L-lysine microspheres were present in close apposition epithelium of the Peyer's patches of rabbits following inoculation into lumen of intestine, which proved that microspheres could be taken up by Peyer's patch. In conclusion, it is suggested that alginate microsphere prepared by spray method, showing a particle size of & $10\;{\mu}m$ and a high loading efficiency, can be used as a model drug for the development of oral vaccine delivery system.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.279-288
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• 2011

The Dexamethasone (DEX) loaded chitosan microspheres were prepared by thermal denaturation and chemical cross-linking method using a dierent concentration of glutaraldehyde as chemical cross-linking agent. The prepared microspheres were evaluated for the percentage of Drug Loading (DL), Encapsulation Efficiency (EE) and surface morphology by Scanning Electron Microscopy (SEM). DL and EE were found to be maximum range of 10.0 to 10.79 % and 58.19 to 64.73 % respectively. The SEM Photographs of the resultant microspheres exhibited fairly smooth surfaces and predominantly spherical in appearance. In addition, Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) shown that there was no interaction between the drug and polymer. In vitro and in vivo release studies revealed that the release of dexamethasone was sustained and extended up to 63 days and effectively controlled by the extent of cross-linking agent. Non-clinical parameters such as paw volume, hematological parameters like Erythrocyte Sedimentation Rate (ESR), Paced Cell Volume (PCV), Total Leucocytes Count (TLC), Hemoglobin (Hb), Differential Cell Count (DCC) were investigated in Fruend's Complete Adjuvant (FCA) induced arthritic rats. Radiology and histopathological studies were also performed in order to evaluate the therapeutic efficacy of the DEX-loaded microspheres in extenuating the rat arthritic model.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.4
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• pp.543-547
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• 2004

Newcastle disease vaccine (NDV)-loaded chitosan microspheres (NDV-CM) were prepared. Stimulatory effects of these NDV-CM on antibody response compared to free NDV were examined in vitro and in vivo. In vitro stimulation of macrophages with virus vaccine resulted in higher number of cells compared to saline-treated control. Both NDV and NDV-CM induced secretion of interleukin-1 (IL-1) in dose dependent manner and the secretion of IL-1 by NDV-CM was delayed compared to free NDV. Irrespective of vaccine formulation, NDV subunit antigen was not effective in preventing mortality of the birds after challenge. However, CM loaded with NDV made of whole viron had antibody responses and protection similar to those shown by ND-K, a commercial inactivated oilemulsion vaccine.