유화법과 분무법에 의해 제조된 경구백신용 알긴산 마이크로스피어의 평가

장혁,지웅길,맹필재,황성주 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.4

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/㎡ to 3 kgf/㎡) 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 μm, larger than that prepared by the w/o emulsion method (about 2 μm), 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 Peyei 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 μm and a high loading efficiency, can be used as a model drug for the development of oral vaccine delivery system.

펠로디핀이 함유된 미립구의 생체이용률

양재헌(Jae Heon Yang),나성범(Sung Bum La),김영일(Young Il Kim),김남순(Nam Soon Kim) 대한약학회 2000 약학회지 Vol.44 No.5

Microspheres of felodipine, which is one of the calcium channel blocker, using a mixture of Eudragit(R) RL, L, E, and cellulose on the base of Eudragit(R) RS were investigated. Cremophor(R) was added to each preparation of polymers in order to increase the release of felodipine from microspheres. Felodipine-loaded microspheres were prepared by a solvent evaporation method, which is based on dispersion of methylene chloride containing felodipine and polymers in 0.5 w/v% polyvinyl alcohol solution. The average diameter based on the size distribution of the felodipine-loaded microspheres was observed to be ca. 40-55mcm. A good and smooth surface were showed in all types of the microspheres. The amount of felodipine loaded was over 90 w/w% in all types of microspheres. The dissolution profiles of felodipine from microspheres were similar with each type of polymer, and about a 60 w/w% of the total amount of felodipine loaded to microsphere was released within 7 hours. Dissolution rate of felodipine from the microsphere was increased by addition of Cremophor(R). After oral administration of the felodipine-loaded microspheres in PVA solution and felodipine alone in PEG solution to rats, respectively, the pharmacokinetic study revealed that (R)the Tmax values of the microspheres were observed in the range of 0.67-1.0hr while that of the felodipine solution was obtained 0.33hr. In addition, the AUC of the microspheres at 0 to 7hr was remarkably increased in comparison to that of felodipine solution. These results revealed that the microspheres based on Eudragit(R) RS could be a good candidate for the controlled release drug delivery system for felodipine.

PLGA 미립구를 이용한 새로운 단회 접종 항원 전달 시스템의 개발

윤미경,최영욱 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.1

A promising approach to the development of a new single-step vaccine, which would eliminate the requirement for multiple injections, involves the encapsulation of antigens into microspheres. Biodegradable poly (lactide-co-gly-colide) (PLGA) microspheres gave us a bright insight for controlling antigen release in a pulsatile fashion, thereby mimicking two or three boosting injections. However, in spite of the above merits, the level of immunization induced by a single-shot vaccination is often lower than two doses of alum-adsorbed antigen. Therefore, optimal modification of the micorsphere is essential for the development of single-step vaccines. In this review, we discuss the stability of antigen in microsphere, safety and non-toxic in human and encapsulation technology. Also, we attempted to outline relevant physicochemical properties on the immunogenicity of microsphere vaccine and attainment of pulsatile release pattern by combination of different microsphere, as well as to analyze immunological data associated with antigen delivery by microsphere. Although a lot of variables are related to the optimized micorsphere formulation, we could conclude that judicious choice of proper polymer type, adjustment of particles size, and appropriate immunization protocol along with a suitable adjuvant might be a crucial factor for the generation of long-lasting immune response from a single-step vaccine formulation employing PLGA microsphere.

Biodegradable uniform microspheres based on solid-in-oil-in-water emulsion for drug delivery: A comparison of homogenization and fluidic device

Ryu, Tae-Kyung,Kim, Sung Eun,Kim, Joo-Hwan,Moon, Seung-Kwan,Choi, Sung-Wook Technomic Pub. Co 2014 Journal of bioactive and compatible polymers Vol.29 No.5

<P>Based on solid-in-oil-in-water emulsification, we fabricated biodegradable poly(ϵ-caprolactone) microspheres containing gentamicin using conventional homogenization and a fluidic device. The feasibility of the poly(ϵ-caprolactone) microspheres as drug carriers was evaluated in terms of encapsulation efficiency, release behavior of gentamicin, and antimicrobial activity. The poly(ϵ-caprolactone) microspheres prepared using a fluidic device (fluidic device microspheres) had a uniform diameter and a smooth surface, whereas the poly(ϵ-caprolactone) microspheres prepared using conventional homogenization (conventional homogenization microspheres) exhibited polydisperse and a porous structure. At 0.3 wt% of gentamicin concentration, the encapsulation efficiencies of the conventional homogenization and fluidic device microspheres were 39.5% and 72.0%, respectively. In addition, a significant amount of gentamicin was only released initially from the conventional homogenization microspheres, whereas the fluidic device microspheres released gentamicin in a sustained manner for 28 days. These results confirmed the superior performances of the uniform fluidic device microspheres for drug delivery system. We further proposed a model for microsphere formation to explain the difference in performance of the conventional homogenization and fluidic device microspheres.</P>

Investigation of the strontium (Sr(II)) adsorption of an alginate microsphere as a low-cost adsorbent for removal and recovery from seawater

Hong, H.J.,Ryu, J.,Park, I.S.,Ryu, T.,Chung, K.S.,Kim, B.G. Academic Press 2016 Journal of environmental management Vol.165 No.-

<P>In this paper, we investigated alginate microspheres as a low-cost adsorbent for strontium (Sr(II)) removal and recovery from seawater. Alginate microspheres have demonstrated a superior adsorption capacity for Sr(II) ions (approximate to 110 mg/g). A Freundlich isotherm model fits well with the Sr(II) adsorption of an alginate microsphere. The mechanism of Sr(II) adsorption is inferred as an ion exchange reaction with Ca(II) ions. The effects of the solution pH and co-existing ions in seawater are also investigated. Except for a pH of 1-2, Sr(II) adsorption capacity is not affected by pH. However, increasing the seawater concentration of metal cations seriously decreases Sr(II) uptake. In particular, highly concentrated (15,000 mg/L) Na(I) ions significantly interfere with Sr(II) adsorption. Sr(II) desorption was performed using 0.1 M HCl and CaCl2. Both regenerants show an excellent desorption efficiency, but the FTIR spectrum reveals that the chemical structure of the microsphere is destroyed after repeated use of HCl. Conversely, CaCl2 successfully desorbed Sr(II) without damage, and the Sr(II) adsorption capacity does not decrease after three repeated uses. The alginate microsphere was also applied to the adsorption of Sr(II) in a real seawater medium. Because of inhibition by co-existing ions, the Sr(II) adsorption capacity was decreased and the adsorption rate was retarded compared with DJ. water. Although the Sr(II) adsorption capacity was decreased, the alginate microsphere still exhibited 17.8 mg/g of Sr(II) uptake in the seawater medium. Considering its excellent Sr(II) uptake in seawater and its reusability, an alginate microsphere is an appropriate cost-effective adsorbent for the removal and recovery of Sr(II) from seawater. (C) 2015 Elsevier Ltd. All rights reserved.</P>

Gold-Decorated Block Copolymer Microspheres with Controlled Surface Nanostructures

Kim, Minsoo P.,Kang, Dong Jin,Jung, Dae-Woong,Kannan, Aravindaraj G.,Kim, Ki-Hyun,Ku, Kang Hee,Jang, Se Gyu,Chae, Weon-Sik,Yi, Gi-Ra,Kim, Bumjoon J. American Chemical Society 2012 ACS NANO Vol.6 No.3

<P>Gold-decorated block copolymer microspheres (BCP-microspheres) displaying various surface morphologies were prepared by the infiltration of Au precursors into polystyrene-<I>b</I>-poly(4-vinylpyridine) (PS-<I>b</I>-P4VP) microspheres. The microspheres were fabricated by emulsifying the PS-<I>b</I>-P4VP polymers in chloroform into a surfactant solution in water, followed by the evaporation of chloroform. The selective swelling of the P4VP domains in the microspheres by the Au precursor under acidic conditions resulted in the formation of Au-decorated BCP-microspheres with various surface nanostructures. As evidenced by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) measurements, dotted surface patterns were formed when microspheres smaller than 800 nm were synthesized, whereas fingerprint-like surface patterns were observed with microspheres larger than 800 nm. Au nanoparticles (NPs) were located inside P4VP domains near the surfaces of the prepared microspheres, as confirmed by TEM. The optical properties of the BCP-microspheres were characterized using UV–vis absorption spectroscopy and fluorescence lifetime measurements. A maximum absorption peak was observed at approximately 580 nm, indicating that Au NPs are densely packed into P4VP domains on the microspheres. Our approach for creating Au-NP-hybrid BCP-microspheres can be extended to other NP systems such as iron-oxide or platinum NPs. These precursors can also be selectively incorporated into P4VP domains and induce the formation of hybrid BCP-microspheres with controlled surface nanostructures.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2012/ancac3.2012.6.issue-3/nn300194z/production/images/medium/nn-2012-00194z_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn300194z'>ACS Electronic Supporting Info</A></P>

Fabrication of covered porous PLGA microspheres using hydrogen peroxide for controlled drug delivery and regenerative medicine

Bae, S.E.,Son, J.S.,Park, K.,Han, D.K. Elsevier Science Publishers 2009 Journal of controlled release Vol.133 No.1

Poly(lactic-co-glycolic acid) (PLGA) microsphere has been a useful tool in delivering therapeutic drugs and biologically active proteins. In this study, a covered porous PLGA microsphere was manufactured using W<SUB>1</SUB>/O/W<SUB>2</SUB> double emulsion solvent evaporation method, utilizing hydrogen peroxide as a novel porogen. An enzymatic reaction between hydrogen peroxide and catalase produced oxygen bubbles and thus many internal pores within microsphere were naturally developed. When different molar ratios between lactide and glycolide in PLGA were examined, the ratio, 50:50 showed the most organized porous microstructure. Higher molecular weight of PLGA seemed to be favorable in creating a porous structure. By testing various concentrations of hydrogen peroxide, it was found that rather concentrated one was more efficient in developing a porous network in the microspheres. The source of the skin layer that covers the whole surface of the microsphere was found to be PLGA, not polyvinyl alcohol (PVA). The residual amount of hydrogen peroxide was negligible after a thorough evaporation of PLGA microsphere. When release profiles of dexamethasone (Dex) with morphologically different microspheres such as, nonporous, covered porous, and porous, were investigated for up to 28 days in vitro, their release patterns were found to be significantly different on a temporal basis. The present work demonstrated that the covered porous PLGA microspheres could be successfully fabricated using hydrogen peroxide and that the covered skin layer on the PLGA microsphere played an important role in determining the characteristic release profiles of Dex.

닥나무 뿌리 추출물을 함유하는 고분자 마이크로입자 제조 및 평가

임형준 ( Hyung Jun Lim ),이진영 ( Jin Young Lee ),김한별 ( Han Byul Kim ),김도훈 ( Do-hoon Kim ),신송석 ( Song Seok Shin ) 대한화장품학회 2013 대한화장품학회지 Vol.39 No.2

본 연구에서는 폴리에틸렌아디페이트와 폴리메틸메타크릴레이트로 구성된 고분자 마이크로입자에 닥나무 뿌리 추출물을 함유시켜 닥나무 뿌리 추출물의 안정도와 상용성을 성공적으로 향상시켰다. 마이크로입자를 구성하는 고분자의 비율에 따라 마이크로입자에 함유된 닥나무 뿌리 추출물의 장기안정도에 미치는 영향을 평가하였다. 폴리에틸렌아디페이트 마이크로입자의 물리적 강도를 높여주기 위하여 폴리메틸메타크릴레이트를 도입하였으며, 이는 마이크로입자에 안정화시킨 닥나무 뿌리 추출물의 안정도에는 큰 영향이 없었다. 광학현미경, 편광현미경, 주사전자현미경을 이용하여 고분자 마이크로입자의 물리적 안정도를 관찰하였고, in vitro 실험을 통하여 고분자 마이크로입자로 안정화된 닥나무 뿌리 추출물의 미백 효과도 잘 유지되고 있음을 확인하였다. This study demonstrate that polymeric microspheres composed of poly (ethylene adipate) (PEA) and poly (methyl methacrylate) (PMMA) can encapsulate and remarkably stabilize Broussonetia kazinoki root extract. We compared the long-term stability and the activity of Broussonetia kazinoki root extract in polymeric microspheres fabricated with different polymer ratio of PEA and PMMA. PMMA was incorporated to the PEA microsphere in order to reinforce the physical strength of microsphere, and there was no noticeable negative effect on the activity of Broussonetia kazinoki root extract. Optical microscope (OM), polarized microscope (PM), and scanning electron microscope (SEM) results showed that PMMA incorporated microspheres were very spherical and had smoothsurface. On the other hand, PEA microspheres showed relatively irregular morphology due to the low physical strength of microspheres. Moreover, the mushroom tyrosinase activities were measured for testing the inhibitory activity of Broussonetia kazinoki root extract encapsulated in polymeric microspheres, and these microspheres showed the effective suppression of mushroom tyrosinase activity. Consequently, polymeric microspheres produced in this study may be beneficial for the research of improving stability and protecting labile substances incorporated into the polymeric microspheres.

Study of comparative aspects of gastroretentive delivery of cefixime trihydrate from microspheres and microsphere based tablets

Brahmeshwar Mishra,Alok Kumar Singh,Sarita Kumari Yadav 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.6

The research was performed to develop and evaluate floating gastroretentive microsphere based tablets of cefixime trihydrate (CFT) which shows poor oral bioavailability (40–50 %) due to narrow absorption window. The microspheres were prepared by varying ratios of hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose using non-aqueous solvent evaporation method. Fourier transform infrared analysis of prepared microspheres demonstrated the compatibility of drug and polymers. Differential scanning calorimetric and X-ray diffraction studies confirmed changes in crystalline structure of CFT within the formulation. Scanning electron microscopy showed spherical and porous nature of microspheres. Microspheres were characterized for particle sizes (70–160 lm), percentage yield (84–95 %), and encapsulation efficiencies (35–80 %). Micrometric parameters such as angle of repose, Carr’s index were in acceptable limit and indicated microsphere elicited free flowing behaviour. Tableted microspheres illustrated buoyancy for more than 12 h as compared to drug tablets. In vitro release of drug was more controlled and prolonged on tableting the microspheres exhibiting biphasic pattern. Kinetically, microspheres followed Fickian (case I) diffusion mechanism while tableted microspheres followed non-Fickian diffusion (anomalous) mechanism for CFT release. Conclusively, tableting of microsphere into swellable and controlled release polymers like HPMC are expected to enhance gastric retention and bioavailability of CFT due to small particle size, changes in crystallinity of CFT, prolonged floating behavior and controlled release profile.

Poly(BMA-co-PEGMA) Microsphere의 합성 및 특성

전용진(Chun, Yong-Jin),조석형(Cho, Suk-Hyung),이건직(Lee, Gun Jik) 한국산학기술학회 2013 한국산학기술학회논문지 Vol.14 No.10

Poly(butyl methacrylate-co-polyethyleneglycol methacrylate)(Poly(BMA-co-PEGMA)) microsphere은 침전중합법 으로 에탄올 용액에서 제조하였으며 마이크로스페어의 입자 크기는 모노머인 BMA와 PEGMA의 농도조건에 따라 140-210nm까지 조절 할 수 있었다. PEGMA의 농도가 증가할 수록 마이크로스페어의 크기가 작아지는 반면 BMA의 농도가 증가하면 마이크로스페어의 입자크기가 증가하였다. Poly(butyl methacrylate-co-polyethyleneglycol methacrylate) (Poly(BMA-co-PEGMA)) microsphere was prepared by precipitation copolymerization of PEGMA and butyl methacrylate in ethanol solution. Microspheres were controlled by experimantal conditions 140nm to 210nm. The particle size of Poly(BMA-co-PEGMA) microspheres was decreased with increasing the concentration of PEGMA and increased with BMA of monomer.