Size-controlled Microbeads through the Influence of the Coalescence Effect in the Emulsification Solvent Evaporation Method

Syed Izhar Haider Abdi; Sing Muk Ng; Jeong Yeon Choi; Ji Min Seo; Jeong Ok Lim

Macromolecular Research, Vol.18, No.7, 668-673, July, 2010

DOI10.1007/s13233-010-0706-7 Export Citation

Size-controlled Microbeads through the Influence of the Coalescence Effect in the Emulsification Solvent Evaporation Method

Syed Izhar Haider Abdi^{1, 2}, Sing Muk Ng^{1, 3}, Jeong Yeon Choi^{1, 2}, Ji Min Seo^{1, 2}, and Jeong Ok Lim^{1, 2, †}

¹Biomedical Research Institute, Kyungpook National University, School of Medicine, Daegu, 702-701, Korea
²Joint Institute for Regenerative Medicine, Kyungpook National University, Hospital, Daegu, 700-721, Korea
³Department of Materials Science and Metallurgy, Kyungpook National University, Daegu, 702-701, Korea

E-mail:

This paper reports a novel, simple, repeatable and cost-effective protocol for producing Ca-alginate beads with controlled sizes ranging from 50-250 μm with a narrow size distribution. The characteristics of the beads depend on the emulsion droplets formed, and the size of the beads can be controlled by manipulating the coalescence factor and the applied mechanical energy, which will also reduce the cost and overall time of the procedure. These results suggest that beads with diameters of 58±5, 69±7, 80±8, 145±11, 195±12 and 225±15 μm (mean diameter ± standard deviation) were easily produced. This was achieved simply by adding a minor amount of Pluronic F-127 (i.e., 0.03%) and controlling the coalescence effect to reduce the stabilization of the emulsion. Therefore, the method has strong potential for mass production on an industrial scale. Furthermore, the solvent evaporation technique successfully evaporated the volatile organic solvent used for emulsification. The beads were proven to be safe via a cell culture study and might be suitable for use in the medical, pharmaceutical and bioengineering field.

Keywords:size control;microbeads;Ca-alginate;emulsification solvent evaporation;coalescence;drug delivery

[References]

Callewaert M, Millot JM, Lesage J, Maquin DL, Levy FE, Int. J. Pharm., 366, 103 (2009)
Sezer AD, Akbuga J, J. Microencapsul., 16(6), 687 (1999)
Wang X, Wenk E, Hu X, Castro GR, Meinel L, Wang X, Li C, Merkle H, Kaplan DL, Biomaterials, 28, 4161 (2007)
Park KS, Jin CM, Kim SH, Rhee JM, Khang G, Han CW, Yang YS, Kim MS, Lee HB, Macromol. Res., 13(4), 285 (2005)
Quong D, Neufeld RJ, Biotechnol. Bioeng., 60, 134 (2000)
Desai KGH, Liu C, Park HJ, J. Microencapsul., 22(4), 363 (2005)
Grant GT, Morris ER, Rees DA, Smith PJC, FEBS Letters, 32, 195 (1973)
Lee SM, Yoo ES, Ghim HD, Lee SJ, Macromol. Res., 17(3), 168 (2009)
Berkland C, Kim K, Pack DW, Pharm. Res., 20, 1055 (2003)
Berkland C, Pollauf E, Pack DW, Kim K, J. Control. Release, 96, 101 (2004)
Chicheportiche D, Reach G, Diabetologia, 31, 54 (1988)
Jalenjak I, Kondo T, J. Pharm. Sci., 70, 456 (2006)
Fundueanu G, Nastruzzi C, Carpov A, Desbrieres J, Rinaudo M, Biomaterials, 20, 1427 (1999)
Sugiura TOS, Izumida Y, Aoyagi Y, Satake M, Ochiai A, Ohkohchi N, Nakajima M, Biomaterials, 16, 3327 (2005)
Chuah AM, Kuroiwa T, Kobayashi I, Zhang X, Nakajima M, Colloids Surf. A: Physicochem. Eng. Asp., 351, 9 (2009)
Tu J, Bolla S, Barr J, Miedema J, Li X, Jasti B, Int. J. Pharm., 30, 171 (2005)
Capretto L, Mazzitelli S, Tosi A, Nastruzzi C, J. Control. Release, 132, 55 (2008)
Poncelet D, Ann. Acad. Sci., 944, 74 (2001)
Fundueanu G, Esposito E, Mihai D, Carpov A, Desbrieres J, Rinaudo M, Nastruzzi C, Int. J. Pharm., 170, 11 (1998)
You JO, Park SB, Park HY, Haam S, Chung CH, Kim WS, J. Microencapsul., 18(4), 521 (2001)
Reis CP, Neufeld RJ, Vilela S, Ribeiro AJ, Veiga F, J. Microencapsul., 23(3), 245 (2006)
Wei Q, Wei W, Tian R, Wang LY, Su ZG, Ma GH, J. Colloid Interface Sci., 323(2), 267 (2008)
Bodmeier R, Ginity RWM, Pharm. Res., 4, 465 (1987)
Thu PB, Bruheim P, Espevik T, Smidsrd O, Shiong PS, Brek GS, Biomaterials, 17, 1069 (1997)
Nilkumhang S, Basit AW, Int. J. Pharm., 377, 135 (2009)
Fu Y, Jin Z, Liu G, Yin Y, Synth. Met., 159, 1744 (2009)
Iwata M, Ginity JWM, J. Microencapsul., 9, 201 (1992)
Mofidi N, Aghai-Moghadam M, Sarbolouki MN, Process Biochem., 35(9), 885 (2000)
Tonga Y, Lib C, Liangc F, Chend J, Zhanga H, Liua G, Suna H, Luonge JHT, Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms, 266, 5041 (2008)
Office of environmental Health Hazard Assessment (www.oehha.ca.gov/water/phg/pdf/dcm.pdf).

[1] Callewaert M, Millot JM, Lesage J, Maquin DL, Levy FE, Int. J. Pharm., 366, 103 (2009)

[2] Sezer AD, Akbuga J, J. Microencapsul., 16(6), 687 (1999)

[3] Wang X, Wenk E, Hu X, Castro GR, Meinel L, Wang X, Li C, Merkle H, Kaplan DL, Biomaterials, 28, 4161 (2007)

[4] Park KS, Jin CM, Kim SH, Rhee JM, Khang G, Han CW, Yang YS, Kim MS, Lee HB, Macromol. Res., 13(4), 285 (2005)

[5] Quong D, Neufeld RJ, Biotechnol. Bioeng., 60, 134 (2000)

[6] Desai KGH, Liu C, Park HJ, J. Microencapsul., 22(4), 363 (2005)

[7] Grant GT, Morris ER, Rees DA, Smith PJC, FEBS Letters, 32, 195 (1973)

[8] Lee SM, Yoo ES, Ghim HD, Lee SJ, Macromol. Res., 17(3), 168 (2009)

[9] Berkland C, Kim K, Pack DW, Pharm. Res., 20, 1055 (2003)

[10] Berkland C, Pollauf E, Pack DW, Kim K, J. Control. Release, 96, 101 (2004)

[11] Chicheportiche D, Reach G, Diabetologia, 31, 54 (1988)

[12] Jalenjak I, Kondo T, J. Pharm. Sci., 70, 456 (2006)

[13] Fundueanu G, Nastruzzi C, Carpov A, Desbrieres J, Rinaudo M, Biomaterials, 20, 1427 (1999)

[14] Sugiura TOS, Izumida Y, Aoyagi Y, Satake M, Ochiai A, Ohkohchi N, Nakajima M, Biomaterials, 16, 3327 (2005)

[15] Chuah AM, Kuroiwa T, Kobayashi I, Zhang X, Nakajima M, Colloids Surf. A: Physicochem. Eng. Asp., 351, 9 (2009)

[16] Tu J, Bolla S, Barr J, Miedema J, Li X, Jasti B, Int. J. Pharm., 30, 171 (2005)

[17] Capretto L, Mazzitelli S, Tosi A, Nastruzzi C, J. Control. Release, 132, 55 (2008)

[18] Poncelet D, Ann. Acad. Sci., 944, 74 (2001)

[19] Fundueanu G, Esposito E, Mihai D, Carpov A, Desbrieres J, Rinaudo M, Nastruzzi C, Int. J. Pharm., 170, 11 (1998)

[20] You JO, Park SB, Park HY, Haam S, Chung CH, Kim WS, J. Microencapsul., 18(4), 521 (2001)

[21] Reis CP, Neufeld RJ, Vilela S, Ribeiro AJ, Veiga F, J. Microencapsul., 23(3), 245 (2006)

[22] Wei Q, Wei W, Tian R, Wang LY, Su ZG, Ma GH, J. Colloid Interface Sci., 323(2), 267 (2008)

[23] Bodmeier R, Ginity RWM, Pharm. Res., 4, 465 (1987)

[24] Thu PB, Bruheim P, Espevik T, Smidsrd O, Shiong PS, Brek GS, Biomaterials, 17, 1069 (1997)

[25] Nilkumhang S, Basit AW, Int. J. Pharm., 377, 135 (2009)

[26] Fu Y, Jin Z, Liu G, Yin Y, Synth. Met., 159, 1744 (2009)

[27] Iwata M, Ginity JWM, J. Microencapsul., 9, 201 (1992)

[28] Mofidi N, Aghai-Moghadam M, Sarbolouki MN, Process Biochem., 35(9), 885 (2000)

[29] Tonga Y, Lib C, Liangc F, Chend J, Zhanga H, Liua G, Suna H, Luonge JHT, Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms, 266, 5041 (2008)

[30] Office of environmental Health Hazard Assessment (www.oehha.ca.gov/water/phg/pdf/dcm.pdf).