PEGylated poly(lactide-co-glycolide) (PLGA) nanoparticulate delivery of docetaxel: Synthesis of diblock copolymers, optimization of preparation variables on formulation characteristics and in vitro release studies

S. Murugesan, S. Ganesan, R.K. Averineni, M. Nahar, P. Mishra, N.K. Jain

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

This study investigates the synthesis of diblock copolymers, the effects of preparation variables on formulation characteristics and the release rate of docetaxel loaded nanoparticles. PLGA-mPEG diblock copolymers were synthesized by ring opening polymerization reactions using stannous octoate as a catalyst and characterized by 1H NMR, FT-IR, and GPC. Docetaxel (antineoplastic) loaded nanoparticles were prepared by the emulsion solvent evaporation technique (o/w emulsification) using sodium cholate as a surfactant. To optimize the preparation conditions of the nanoparticles, the effects of preparation variables such as amount of polymer, organic to aqueous phase ratio, surfactant concentration and drug loading on the formulation characteristics were studied and evaluated in terms of particle size and drug entrapment efficiency (DEE). The nanoparticles were characterized for their size, DEE, surface charge, and surface morphology. Further, effects of the mPEG chain length (mPEG 2 and 5 KDa) in synthesis and nanoparticles formulation were examined. The results showed that the mPEG chain affected the yield and molecular weight of the copolymer substantially, whereas, least on the drug loading and nanoparticles size. The release behavior of docetaxel from the polymer matrix exhibited a biphasic pattern that is characterized by an initial burst, followed by a slower sustained release in all formulations. Copyright © 2007 American Scientific Publishers All rights reserved.
Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalJournal of Biomedical Nanotechnology
Volume3
Issue number1
DOIs
Publication statusPublished - 2007
Externally publishedYes

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docetaxel
Polyglactin 910
Nanoparticles
Block copolymers
Surface-Active Agents
Pharmaceutical Preparations
Polymers
Surface active agents
Sodium Cholate
Emulsification
Organic polymers
Ring opening polymerization
Surface charge
Emulsions
Polymer matrix
Chain length
Particle Size
Polymerization
Antineoplastic Agents
Surface morphology

Cite this

@article{c45b6bb8632944aaa9ee68eddc7822cc,
title = "PEGylated poly(lactide-co-glycolide) (PLGA) nanoparticulate delivery of docetaxel: Synthesis of diblock copolymers, optimization of preparation variables on formulation characteristics and in vitro release studies",
abstract = "This study investigates the synthesis of diblock copolymers, the effects of preparation variables on formulation characteristics and the release rate of docetaxel loaded nanoparticles. PLGA-mPEG diblock copolymers were synthesized by ring opening polymerization reactions using stannous octoate as a catalyst and characterized by 1H NMR, FT-IR, and GPC. Docetaxel (antineoplastic) loaded nanoparticles were prepared by the emulsion solvent evaporation technique (o/w emulsification) using sodium cholate as a surfactant. To optimize the preparation conditions of the nanoparticles, the effects of preparation variables such as amount of polymer, organic to aqueous phase ratio, surfactant concentration and drug loading on the formulation characteristics were studied and evaluated in terms of particle size and drug entrapment efficiency (DEE). The nanoparticles were characterized for their size, DEE, surface charge, and surface morphology. Further, effects of the mPEG chain length (mPEG 2 and 5 KDa) in synthesis and nanoparticles formulation were examined. The results showed that the mPEG chain affected the yield and molecular weight of the copolymer substantially, whereas, least on the drug loading and nanoparticles size. The release behavior of docetaxel from the polymer matrix exhibited a biphasic pattern that is characterized by an initial burst, followed by a slower sustained release in all formulations. Copyright {\circledC} 2007 American Scientific Publishers All rights reserved.",
author = "S. Murugesan and S. Ganesan and R.K. Averineni and M. Nahar and P. Mishra and N.K. Jain",
note = "Cited By :17 Export Date: 10 November 2017 Correspondence Address: Jain, N.K.; Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar 470003, India Chemicals/CAS: cholic acid, 32500-01-9, 361-09-1, 81-25-4; docetaxel, 114977-28-5; polyglactin, 26780-50-7, 34346-01-5 Manufacturers: Cipla, India References: Hans, M.L., Lowman, A.M., Biodegradable nanoparticles for drug delivery and targeting (2002) Curr Opin. Solid State Mater Sci, 6, p. 319; Jain, R.A., The manufacturing techniques of various drug loaded biodegradable poly(lactic-co-glycolide) (PLGA) devices (2000) Biomaterials, 21, p. 2475; Vert, M., Schwach, G., Engel, R., Coudane, J., Something new in the field of PLA/GA bioresobable polymers? (1998) J Control Release, 53, p. 85; Illum, L., Davis, S.S., Muller, R.H., Mark, E., West, P., The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with block-copolymer-polaxamine 908 (1987) Life Sci, 40, p. 367; Illum, L., Davis, S.S., The effect of hydrophilic coatings on the uptake of colloidal particles with mouse peritoneal macrophages (1986) Int. J. Pharm, 29, p. 53; Porter, C.J., Moghimi, S.M., Illum, L., Davis, S.S., The polyoxyethylene/polyoxypropylene block co-polymer polaxamer-407 selectively redirects intravenously injected microspheres to sinusoidal endothelial cells of rabbit bone marrow (1992) FEBS Lett, 305, p. 62; Avgoustakis, K., Preparation, properties and possible applications in drug delivery (2004) Curr Drug Deliv, 1, p. 321. , Pegylated Poly(Lactide) and Poly(Lactide-Co-Glycolide) nanoparticles; Gref, R., Domp, A., Quellec, P., Blunk, T., Muller, R.H., Verbavatz, J.M., Langer, R., The controlled intravenous delivery of drugs using PEG coated sterically stabilized nanospheres (1995) Adv. Drug Deliv. Rev, 16, p. 215; Beletsi, A., Leotiadis, L., Klepetsanis, P., Ithakissios, D.S., Avgoustakis, K., Effect of preparative variables on the properties of poly(dl-lactide-co-glycolide) methoxy poly(ethylene glycol) copolymers related to their application in controlled drug delivery (1999) Int. J Pharm, 192, p. 187; Qin, L.Y., Bae, Y.H., Polymer architecture and drug delivery (2006) Pharm. Res, 23, p. 1; Gref, R., Minamitake, Y., Perachia, M.T., Trubetskoy, V., Torchilin, V., Langer, R., Biodegradable long circulating polymeric nanospheres (1994) Science, 263, p. 1600; Stolink, S., Illium, L., Davis, S.S., Long circulating micro particulate drug carriers (1995) Adv. Drug Deliv. Rev, 16, p. 195; Bazile, D., Prudhomme, C., Bassoullet, M.T., Marlard, A., Spenlenhauer, G., veillard, M., Stealth Me-PEG-PLA nanoparticles avoid uptake by the mononuclear phagocyte system (1995) J. Pharm. Sci, 84, p. 493; m. T. Peracchia, R. Gref, Y. Minamitake, A. Domb, N. Lotan, and R. Langer, PEG coated nanospheres from amphilic diblock and multiblock copolymer; investigation of their drug encapsulation and release characteristics. J. Control Release 46, 223 (1997); Strom, G., Beliot, S.O., Daemen, T., Lasic, D.D., Surface modification of nanoparticies to oppose uptake by the mononuclear phagocyte system (1995) Adv. Drug Deliv. Rev, 17, p. 191; Rowinsky, E.K., The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents (1997) Ann. Rev. Med, 48, p. 353; Capri, G., Tarenzi, E., Fulfaro, F., Gianni, L., The role of taxanes in the treatment of breast cancer (1996) Semin. Oncol, 23, p. 68; Kaye, S.B., (1995) Taxoids. Eur. J. Cancer, 31 A, p. 824; Immordino, M.L., Brusa, P., Arpicco, S., Stella, B., Dosio, F., Cattel, L., Preparation, characterization, cytotoxicity, and pharmacokinetics of liposomes containing docetaxel (2003) J. Control Release, 91, p. 417; Grosse, P.Y., Bressolle, F., Pinguet, F., In vitro modulation of doxorubicin and docetaxel antitumoral activity by methyl-β-cyclodextrin (1998) Eur. J. Cancer, 34, p. 168; Nahar, M., Dutta, T., Senthilkumar, M., Asthana, A., Mishtra, D., Rajkumar, V., Tare, M., Jain, N.K., Functional polymeric nanoparticles: Efficient and promising tool for active delivery of bioactives Crit. Rev. Ther. Drug Carr. Syst, , in press; Li, Y.P., Pei, Y.Y., Zhang, X.Y., Gu, Z.H., Zhou, Z.H., Yuan, W.F., Zhou, J.J., Gan, X.J., PEGylated PLGA nanoparticles as protein carrier; synthesis, preparation and bio distribution in rats (2001) J. Control Release, 71, p. 203; Jeong, B., Bae, Y.H., Kim, S.W., Biodegradable thermosensitive micelles of PEG-PLGA-PEG triblock copolymers (1999) Colloids Surf. B Biointerfaces, 16, p. 185; Dorta, M.J., Munguia, O., Llabres, M., Molecular weight, composition, and chain structure (1993) Int. J. Pharm, 100, p. 9. , Effects of polymerization variables on PLGA properties; Dong, Y., Feng, S.S., Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticies for controlled delivery of anticancer drugs (2004) Biomaterials, 25, p. 2843; Rubiana, M.M., Raul, C.E., Effect of formulation variables on size distribution (2005) Int. J. Pharm, 290, p. 137. , PLGA nanoparticles containing praziquantel; Sahoo, S.K., Panyam, J., Prabha, S., Labhasetwar, V., Residual polyvinyl alcohol associated with poly(lactic-co-glycolide) nanoparticles affects their physical properties and cellular uptake (2002) J. Control Release, 82, p. 105; Avgoustakis, K., Beletsi, A., Panagi, Z., Klepetsanis, P., Karydas, A.G., Ithakissios, D.S., PLGA-mPEG nanoparticles of cisplatin in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties (2002) J. Control Release, 79, p. 123",
year = "2007",
doi = "10.1166/jbn.2007.012",
language = "English",
volume = "3",
pages = "52--60",
journal = "Journal of Biomedical Nanotechnology",
issn = "1550-7033",
publisher = "American Scientific Publishers",
number = "1",

}

PEGylated poly(lactide-co-glycolide) (PLGA) nanoparticulate delivery of docetaxel: Synthesis of diblock copolymers, optimization of preparation variables on formulation characteristics and in vitro release studies. / Murugesan, S.; Ganesan, S.; Averineni, R.K.; Nahar, M.; Mishra, P.; Jain, N.K.

In: Journal of Biomedical Nanotechnology, Vol. 3, No. 1, 2007, p. 52-60.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PEGylated poly(lactide-co-glycolide) (PLGA) nanoparticulate delivery of docetaxel: Synthesis of diblock copolymers, optimization of preparation variables on formulation characteristics and in vitro release studies

AU - Murugesan, S.

AU - Ganesan, S.

AU - Averineni, R.K.

AU - Nahar, M.

AU - Mishra, P.

AU - Jain, N.K.

N1 - Cited By :17 Export Date: 10 November 2017 Correspondence Address: Jain, N.K.; Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar 470003, India Chemicals/CAS: cholic acid, 32500-01-9, 361-09-1, 81-25-4; docetaxel, 114977-28-5; polyglactin, 26780-50-7, 34346-01-5 Manufacturers: Cipla, India References: Hans, M.L., Lowman, A.M., Biodegradable nanoparticles for drug delivery and targeting (2002) Curr Opin. Solid State Mater Sci, 6, p. 319; Jain, R.A., The manufacturing techniques of various drug loaded biodegradable poly(lactic-co-glycolide) (PLGA) devices (2000) Biomaterials, 21, p. 2475; Vert, M., Schwach, G., Engel, R., Coudane, J., Something new in the field of PLA/GA bioresobable polymers? (1998) J Control Release, 53, p. 85; Illum, L., Davis, S.S., Muller, R.H., Mark, E., West, P., The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with block-copolymer-polaxamine 908 (1987) Life Sci, 40, p. 367; Illum, L., Davis, S.S., The effect of hydrophilic coatings on the uptake of colloidal particles with mouse peritoneal macrophages (1986) Int. J. Pharm, 29, p. 53; Porter, C.J., Moghimi, S.M., Illum, L., Davis, S.S., The polyoxyethylene/polyoxypropylene block co-polymer polaxamer-407 selectively redirects intravenously injected microspheres to sinusoidal endothelial cells of rabbit bone marrow (1992) FEBS Lett, 305, p. 62; Avgoustakis, K., Preparation, properties and possible applications in drug delivery (2004) Curr Drug Deliv, 1, p. 321. , Pegylated Poly(Lactide) and Poly(Lactide-Co-Glycolide) nanoparticles; Gref, R., Domp, A., Quellec, P., Blunk, T., Muller, R.H., Verbavatz, J.M., Langer, R., The controlled intravenous delivery of drugs using PEG coated sterically stabilized nanospheres (1995) Adv. Drug Deliv. Rev, 16, p. 215; Beletsi, A., Leotiadis, L., Klepetsanis, P., Ithakissios, D.S., Avgoustakis, K., Effect of preparative variables on the properties of poly(dl-lactide-co-glycolide) methoxy poly(ethylene glycol) copolymers related to their application in controlled drug delivery (1999) Int. J Pharm, 192, p. 187; Qin, L.Y., Bae, Y.H., Polymer architecture and drug delivery (2006) Pharm. Res, 23, p. 1; Gref, R., Minamitake, Y., Perachia, M.T., Trubetskoy, V., Torchilin, V., Langer, R., Biodegradable long circulating polymeric nanospheres (1994) Science, 263, p. 1600; Stolink, S., Illium, L., Davis, S.S., Long circulating micro particulate drug carriers (1995) Adv. Drug Deliv. Rev, 16, p. 195; Bazile, D., Prudhomme, C., Bassoullet, M.T., Marlard, A., Spenlenhauer, G., veillard, M., Stealth Me-PEG-PLA nanoparticles avoid uptake by the mononuclear phagocyte system (1995) J. Pharm. Sci, 84, p. 493; m. T. Peracchia, R. Gref, Y. Minamitake, A. Domb, N. Lotan, and R. Langer, PEG coated nanospheres from amphilic diblock and multiblock copolymer; investigation of their drug encapsulation and release characteristics. J. Control Release 46, 223 (1997); Strom, G., Beliot, S.O., Daemen, T., Lasic, D.D., Surface modification of nanoparticies to oppose uptake by the mononuclear phagocyte system (1995) Adv. Drug Deliv. Rev, 17, p. 191; Rowinsky, E.K., The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents (1997) Ann. Rev. Med, 48, p. 353; Capri, G., Tarenzi, E., Fulfaro, F., Gianni, L., The role of taxanes in the treatment of breast cancer (1996) Semin. Oncol, 23, p. 68; Kaye, S.B., (1995) Taxoids. Eur. J. Cancer, 31 A, p. 824; Immordino, M.L., Brusa, P., Arpicco, S., Stella, B., Dosio, F., Cattel, L., Preparation, characterization, cytotoxicity, and pharmacokinetics of liposomes containing docetaxel (2003) J. Control Release, 91, p. 417; Grosse, P.Y., Bressolle, F., Pinguet, F., In vitro modulation of doxorubicin and docetaxel antitumoral activity by methyl-β-cyclodextrin (1998) Eur. J. Cancer, 34, p. 168; Nahar, M., Dutta, T., Senthilkumar, M., Asthana, A., Mishtra, D., Rajkumar, V., Tare, M., Jain, N.K., Functional polymeric nanoparticles: Efficient and promising tool for active delivery of bioactives Crit. Rev. Ther. Drug Carr. Syst, , in press; Li, Y.P., Pei, Y.Y., Zhang, X.Y., Gu, Z.H., Zhou, Z.H., Yuan, W.F., Zhou, J.J., Gan, X.J., PEGylated PLGA nanoparticles as protein carrier; synthesis, preparation and bio distribution in rats (2001) J. Control Release, 71, p. 203; Jeong, B., Bae, Y.H., Kim, S.W., Biodegradable thermosensitive micelles of PEG-PLGA-PEG triblock copolymers (1999) Colloids Surf. B Biointerfaces, 16, p. 185; Dorta, M.J., Munguia, O., Llabres, M., Molecular weight, composition, and chain structure (1993) Int. J. Pharm, 100, p. 9. , Effects of polymerization variables on PLGA properties; Dong, Y., Feng, S.S., Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticies for controlled delivery of anticancer drugs (2004) Biomaterials, 25, p. 2843; Rubiana, M.M., Raul, C.E., Effect of formulation variables on size distribution (2005) Int. J. Pharm, 290, p. 137. , PLGA nanoparticles containing praziquantel; Sahoo, S.K., Panyam, J., Prabha, S., Labhasetwar, V., Residual polyvinyl alcohol associated with poly(lactic-co-glycolide) nanoparticles affects their physical properties and cellular uptake (2002) J. Control Release, 82, p. 105; Avgoustakis, K., Beletsi, A., Panagi, Z., Klepetsanis, P., Karydas, A.G., Ithakissios, D.S., PLGA-mPEG nanoparticles of cisplatin in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties (2002) J. Control Release, 79, p. 123

PY - 2007

Y1 - 2007

N2 - This study investigates the synthesis of diblock copolymers, the effects of preparation variables on formulation characteristics and the release rate of docetaxel loaded nanoparticles. PLGA-mPEG diblock copolymers were synthesized by ring opening polymerization reactions using stannous octoate as a catalyst and characterized by 1H NMR, FT-IR, and GPC. Docetaxel (antineoplastic) loaded nanoparticles were prepared by the emulsion solvent evaporation technique (o/w emulsification) using sodium cholate as a surfactant. To optimize the preparation conditions of the nanoparticles, the effects of preparation variables such as amount of polymer, organic to aqueous phase ratio, surfactant concentration and drug loading on the formulation characteristics were studied and evaluated in terms of particle size and drug entrapment efficiency (DEE). The nanoparticles were characterized for their size, DEE, surface charge, and surface morphology. Further, effects of the mPEG chain length (mPEG 2 and 5 KDa) in synthesis and nanoparticles formulation were examined. The results showed that the mPEG chain affected the yield and molecular weight of the copolymer substantially, whereas, least on the drug loading and nanoparticles size. The release behavior of docetaxel from the polymer matrix exhibited a biphasic pattern that is characterized by an initial burst, followed by a slower sustained release in all formulations. Copyright © 2007 American Scientific Publishers All rights reserved.

AB - This study investigates the synthesis of diblock copolymers, the effects of preparation variables on formulation characteristics and the release rate of docetaxel loaded nanoparticles. PLGA-mPEG diblock copolymers were synthesized by ring opening polymerization reactions using stannous octoate as a catalyst and characterized by 1H NMR, FT-IR, and GPC. Docetaxel (antineoplastic) loaded nanoparticles were prepared by the emulsion solvent evaporation technique (o/w emulsification) using sodium cholate as a surfactant. To optimize the preparation conditions of the nanoparticles, the effects of preparation variables such as amount of polymer, organic to aqueous phase ratio, surfactant concentration and drug loading on the formulation characteristics were studied and evaluated in terms of particle size and drug entrapment efficiency (DEE). The nanoparticles were characterized for their size, DEE, surface charge, and surface morphology. Further, effects of the mPEG chain length (mPEG 2 and 5 KDa) in synthesis and nanoparticles formulation were examined. The results showed that the mPEG chain affected the yield and molecular weight of the copolymer substantially, whereas, least on the drug loading and nanoparticles size. The release behavior of docetaxel from the polymer matrix exhibited a biphasic pattern that is characterized by an initial burst, followed by a slower sustained release in all formulations. Copyright © 2007 American Scientific Publishers All rights reserved.

U2 - 10.1166/jbn.2007.012

DO - 10.1166/jbn.2007.012

M3 - Article

VL - 3

SP - 52

EP - 60

JO - Journal of Biomedical Nanotechnology

JF - Journal of Biomedical Nanotechnology

SN - 1550-7033

IS - 1

ER -