Freezing/Thawing Processing of PVA in the Preparation of Structured Microspheres for Protein Drug Delivery

MinKyung Lee; Harim Bae; Sona Lee; Nae-oh Chung; Hyeseung Lee; Soyoung Choi; Sunae Hwang; Jonghwi Lee

Macromolecular Research, Vol.19, No.2, 130-136, February, 2011

DOI10.1007/s13233-011-0203-7 Export Citation

Freezing/Thawing Processing of PVA in the Preparation of Structured Microspheres for Protein Drug Delivery

MinKyung Lee, Harim Bae, Sona Lee, Nae-oh Chung, Hyeseung Lee, Soyoung Choi, Sunae Hwang, and Jonghwi Lee^†

Department of Chemical Engineering and Materials Science, Chung-Ang University, Seoul, 156-756, Korea

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Drug stability and sustained release issues are important areas in drug-delivery research. The sustained release of proteins can be achieved by their encapsulation with a hydrophobic polymer, but this requires the proteins to be protected from the harsh processing environments of organic solvents and mechanical force. Preencapsulation with poly(vinyl alcohol) (PVA) using a freeze/thaw method has been shown to allow successful protection and sustained release. This study examined the effects of freezing/thawing on PVA encapsulation in the preparation of PVA-PLGA composite particles. Freezing/thawing slightly improved the crystalline peaks and the heat of fusion of PVA, but more distinct differences were observed when the properties of the surface layers were probed by AFM. The hardness of particles’ surfaces increased with increasing number of freezing/thawing cycles, whereas the adhesion force with an AFM cantilever tip decreased. The mean particle size and entrapment efficiency decreased. These results suggest that surface hardening is the major mechanism responsible for the sustained release characteristics.

Keywords:nanoparticles;particle size;protein drug;dispersion;particle engineering.

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[Referenced By]

[Related Articles]

[1] Sinha V, Trehan A, J. Control. Release, 90, 261 (2003)

[2] Cleland J, Protein Delivery, 10, 1 (2002)

[3] Herrmann J, Bodmeier R, J. Control. Release, 36, 63 (1995)

[4] Zhao H, Saatchi K, Hafeli U, J. Magn. Magn. Mater., 321, 1356 (2009)

[5] Farokhzad O, Expert Opin. Drug. Del., 5, 927 (2008)

[6] Putney S, Burke P, Nat. Biotechnol., 16, 153 (1998)

[7] Li J, Wang N, Wu X, J. Control. Release, 56, 117 (1998)

[8] Wang N, Wu X, Li J, Pharm. Res., 16, 1430 (1999)

[9] Hong KH, Sun G, J. Appl. Polym. Sci., 116(4), 2418 (2010)

[10] Vrana N, et al., J. Tissue Eng. Regen. M., 3, 567 (2009)

[11] Simoes MM, de Oliveira MG, J. Biomed. Mater. Res. Part B: Appl. Biomater., 93B, 416 (2010)

[12] Szucs A, Haraszti T, Dekany I, Fendler JH, J. Phys. Chem. B, 105(43), 10579 (2001)

[13] Beach ER, Tormoen GW, Drelich J, Han R, J. Colloid Interface Sci., 247(1), 84 (2002)

[14] Tortonese M, Kirk M, Proceeding of International Society for Optics and Photonics, 1997, vol. 3009, p53-60.

[15] Sindel U, Zimmermann I, Powder Technol., 117(3), 247 (2001)

[16] Fuji M, Machida K, Takei T, Watanabe T, Chikazawa M, Langmuir, 15(13), 4584 (1999)

[17] Xiao XD, Qian LM, Langmuir, 16(21), 8153 (2000)

[18] Berard V, Lesniewska E, Andres C, Pertuy D, Laroche C, Pourcelot Y, Int. J. Pharm., 232, 213 (2002)

[19] Ducker W, Senden T, Pashley R, Nature, 353, 239 (1991)

[20] Larson I, Drummond CJ, Chan DYC, Grieser F, J. Am. Chem. Soc., 115, 11885 (1993)

[21] Villarrubia J, Surf. Sci., 321, 287 (1994)

[22] Louey M, Mulvaney P, Stewart P, J. Pharmaceut. Biomed. Anal., 25, 559 (2001)

[23] Eve JK, Patel N, Luk SY, Ebbens SJ, Roberts CJ, Int. J. Pharm., 238, 17 (2002)

[24] Sader JE, Larson I, Mulvaney P, White LR, Rev. Sci. Instrum., 66, 3789 (1995)

[25] Cleveland JP, Manne S, Bocek D, Hansma PK, Rev. Sci. Instrum., 64, 403 (1993)

[26] Hassan C, Stewart J, Peppas N, Eur. J. Pharm. Biopharm., 49, 161 (2000)

[27] Hassan CM, Peppas NA, Macromolecules, 33(7), 2472 (2000)