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Paklitaksel yüklü nanopartiküllerin formülasyonu ve in vitro incelenmesi

Year 2013, Issue: 1, 25 - 40, 01.01.2013

Abstract

Bu çalışmada, paklitaksel yüklü PLGA nanopartikülleri emülsifikasyon-solvent difüzyon metodu kullanılarak hazırlanmış ve polimer ve yüzey aktif madde konsantrasyonunun paklitaksel yüklenmiş PLGA nanopartiküllerini partikül büyüklüğü, zeta potansiyel, enkapsülasyon etkinliği ve in vitro salım oranı üzerine etkisi incelenmiştir. Hazırlanan nanopartiküllerin ortalama partikül büyüklüğünün 190 ve 235 nm arasında olduğu gözlemlenmiştir. Paklitakselin nanopartiküllerin içine ankapsülasyon etkinliği %53-89 arasında bulunmuş olup nanopartiküllerin salım profillerinde başlangıçta patlama etkisini takiben 7 günlük kontrollü salım gözlemlenmiştir. In vitro sitotoksisite çalışmaları ilaç yüklü nanopartikül formülasyonlarının yüklenmemiş olanlara kıyasla daha sitotoksik olduğunu göstermiştir. Yapılan çalışmalar sonucunda, hazırlanan formülasyonun paklitaksel taşınmasında kullanılabileceği bulunmuştur.

References

  • Bayındır ZS, Yuksel N. Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery, J Pharm Sci, 99,2049-60. (2009)
  • Budhian A, Winey KI, Siegel SJ. Production of haloperidol loaded PLGA nanoparticles for extended controlled drug release of haloperidol, J Microencapsulation, 22,773-85. (2005)
  • Byrne JD, Betancourt T, Brannon-Peppas L.: Active targeting schemes for nanoparticle systems in cancer therapeutics, Adv Drug Deliv Rev, 60,1615-26. (2008)
  • Chakravarthi SS, Robinson DH. Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles, Int J Pharm, 409,111-20. (2011)
  • Chawla JS, Amiji MM. Biodegradable poly(o-caprolactone) nanoparticles for tumor tar- geted delivery of tamoxifen, Int J Pharm, 249,127-38. (2002)
  • Dinarvand R, Sepehri N, Manoochehri S, Rouhani H, Atyabi F. Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents, Int J Nanomedicine, 6,877- 95. (2011)
  • Feng S, Chien S. Chemotherapeutic engineering: application and further development of chemical engineering principles for chemotherapy of cancer and other diseases, Chem Eng Sci, 4087 – 114. (2003)
  • Feng S, Huang G. Effects of emulsifiers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymers, J Control Release, 71,53-69. (2001)
  • Gursoy N, Garrigue JS, Razafindratsita A, Lambert G, Benita S. Excipient effects on in vitro cytotoxicity of a novel paclitaxel self-emulsifying drug delivery system, J Pharm Sci, 92,2411-8. (2003)
  • Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment, Urol Oncol, 26,57-64. (2008)
  • ICH. Q2(R1) Validation of Analytical Procedures: Text and Methodology. (2005)
  • Jackson JK, Hung T, Letchford K, Burt HM. The characterization of paclitaxel-loaded microspheres manufactured from blends of poly(lactic-co-glycolic acid) (PLGA) and low molecular weight diblock copolymers, Int J Pharm, 342,6-17. (2007)
  • Jin C, Bai L, Wu H, Song W, Guo G, Dou K. Cytotoxicity of paclitaxel incorporated in PLGA nanoparticles on hypoxic human tumor cells, Pharm Res, 26,1776-84. (2009)
  • Knowles MA, Selby P, New York: Oxford University Press. (2005)
  • Lu JM, Wang X, Marin-Muller C, Wang H, Lin PH, et al. Current advances in research and clinical applications of PLGA-based nanotechnology, Expert Rev Mol Diagn, 9,325- 41. (2009)
  • Lundberg BB, Risovic V, Ramaswamy M, Wasan KM. A lipophilic paclitaxel deriva- tive incorporated in a lipid emulsion for parenteral administration, J Control Release, 86,93-100. (2003)
  • Mainardes RM, Evangelista RC. PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution, Int J Pharm, 290,137-44. (2005)
  • Mukherjee B, Santra K, Pattnaik G, Ghosh S. Preparation, characterization and in- vitro evaluation of sustained release protein-loaded nanoparticles based on biodegrad- able polymers, Int J Nanomedicine, 3,487-96. (2008)
  • Murakami H, Kobayashi M, Takeuchi H, Kawashima Y. Preparation of poly(DL-lactide- co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method, Int J Pharm, 187,143-52. (1999)
  • Ooya T, Lee J, Park K.: Effects of ethylene glycol-based graft, star-shaped, and den- dritic polymers on solubilization and controlled release of paclitaxel, J Control Release, 93,121-7. (2003)
  • Ozturk K, Caban S, Kozlu S, Kadayifci E, Yerlikaya F, Capan Y. The influence of tech- nological parameters on the physicochemical properties of blank PLGA nanoparticles, Pharmazie, 65,665-9. (2010)
  • Panchagnula R. Pharmaceutical aspects of paclitaxel, Int J Pharm, 1-15. (1998)
  • Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy, Nature Nanotech, 2,751 - 60. (2007)
  • Sharma A, Sharma US, Straubinger RM. Paclitaxel-liposomes for intracavitar therapy of intraperitoneal P388 leukemia, Cancer Lett, 107,265-72. (1996)
  • Songa KC, Lee HS, Chounga Y, In Choa K, Ahn Y, Choi EJ. The effect of type of organic phase solvents on the particle size of poly(d,l-lactide-co-glycolide) nanoparticles, Col- loid Surface A, 276,162–7. (2006)
  • Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices, J Control Release, 70,1-20. (2001)
  • Sparreboom A, Scripture CD, Trieu V, Williams PJ, De T, et al. Comparative preclini- cal and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol), Clin Cancer Res, 11,4136-43. (2005)
  • Twentyman PR, Luscombe M. A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity, Br J Cancer, 56,279-85. (1987)
  • Vicari L, Musumeci T, Giannone I, Adamo L, Conticello C, et al. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity, BMC Cancer, 8,212. (2008)
  • Yang Q, Owusu-Ababio G. Biodegradable progesteronemicrosphere delivery system for osteoporosis therapy, Drug Dev Ind Pharm, 26, 61–70. (2000)
  • Yerlikaya F, Ozgen A, Vural I, Guven O, Karaagaoglu E, Khan MA, Capan Y. Develop- ment and evaluation of paclitaxel nanoparticles using a quality-by-design approach, J Pharm Sci., 102, 3748-61. (2013)
  • Zambaux MF, Bonneaux F, Gref R, Maincent P, Dellacherie E, et al. Influence of experi- mental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method, J Control Release, 50,31-40. (1998)
  • Zhang L, He Y, Ma G, Song C, Sun H. Paclitaxel-loaded polymeric micelles based on poly(varepsilon-caprolactone)-poly(ethylene glycol)-poly(varepsilon-caprolactone) tri- block copolymers: in vitro and in vivo evaluation, Nanomedicine, 8,925-34. (2012)

Formulation and in Vitro Evaluation of Paclitaxel Loaded Nanoparticles

Year 2013, Issue: 1, 25 - 40, 01.01.2013

Abstract

In this study, paclitaxel loaded PLGA nanoparticles were prepared using emulsification-solvent diffusion method and the influences of polymer and emulsifier concentrations on particle size, zeta potential, encapsulation efficiency and in vitro release rate of the paclitaxel loaded PLGA nanoparticles were evaluated. It was observed that average particle size of the prepared nanoparticles were between 190 and 235 nm. The encapsulation efficiency of paclitaxel into the nanoparticles was between 53-89% and the release profiles of the nanoparticles exhibited an initial burst effect followed by a controlled release for 7 days. In vitro cytotoxicity studies showed that drug loaded nanoparticle formulation was more cytotoxic than the blank nanoparticle formulation. According to the results of the studies performed, it can be concluded that prepared nanoparticle formulations may be a considerable approach for paclitaxel delivery.

References

  • Bayındır ZS, Yuksel N. Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery, J Pharm Sci, 99,2049-60. (2009)
  • Budhian A, Winey KI, Siegel SJ. Production of haloperidol loaded PLGA nanoparticles for extended controlled drug release of haloperidol, J Microencapsulation, 22,773-85. (2005)
  • Byrne JD, Betancourt T, Brannon-Peppas L.: Active targeting schemes for nanoparticle systems in cancer therapeutics, Adv Drug Deliv Rev, 60,1615-26. (2008)
  • Chakravarthi SS, Robinson DH. Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles, Int J Pharm, 409,111-20. (2011)
  • Chawla JS, Amiji MM. Biodegradable poly(o-caprolactone) nanoparticles for tumor tar- geted delivery of tamoxifen, Int J Pharm, 249,127-38. (2002)
  • Dinarvand R, Sepehri N, Manoochehri S, Rouhani H, Atyabi F. Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents, Int J Nanomedicine, 6,877- 95. (2011)
  • Feng S, Chien S. Chemotherapeutic engineering: application and further development of chemical engineering principles for chemotherapy of cancer and other diseases, Chem Eng Sci, 4087 – 114. (2003)
  • Feng S, Huang G. Effects of emulsifiers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymers, J Control Release, 71,53-69. (2001)
  • Gursoy N, Garrigue JS, Razafindratsita A, Lambert G, Benita S. Excipient effects on in vitro cytotoxicity of a novel paclitaxel self-emulsifying drug delivery system, J Pharm Sci, 92,2411-8. (2003)
  • Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment, Urol Oncol, 26,57-64. (2008)
  • ICH. Q2(R1) Validation of Analytical Procedures: Text and Methodology. (2005)
  • Jackson JK, Hung T, Letchford K, Burt HM. The characterization of paclitaxel-loaded microspheres manufactured from blends of poly(lactic-co-glycolic acid) (PLGA) and low molecular weight diblock copolymers, Int J Pharm, 342,6-17. (2007)
  • Jin C, Bai L, Wu H, Song W, Guo G, Dou K. Cytotoxicity of paclitaxel incorporated in PLGA nanoparticles on hypoxic human tumor cells, Pharm Res, 26,1776-84. (2009)
  • Knowles MA, Selby P, New York: Oxford University Press. (2005)
  • Lu JM, Wang X, Marin-Muller C, Wang H, Lin PH, et al. Current advances in research and clinical applications of PLGA-based nanotechnology, Expert Rev Mol Diagn, 9,325- 41. (2009)
  • Lundberg BB, Risovic V, Ramaswamy M, Wasan KM. A lipophilic paclitaxel deriva- tive incorporated in a lipid emulsion for parenteral administration, J Control Release, 86,93-100. (2003)
  • Mainardes RM, Evangelista RC. PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution, Int J Pharm, 290,137-44. (2005)
  • Mukherjee B, Santra K, Pattnaik G, Ghosh S. Preparation, characterization and in- vitro evaluation of sustained release protein-loaded nanoparticles based on biodegrad- able polymers, Int J Nanomedicine, 3,487-96. (2008)
  • Murakami H, Kobayashi M, Takeuchi H, Kawashima Y. Preparation of poly(DL-lactide- co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method, Int J Pharm, 187,143-52. (1999)
  • Ooya T, Lee J, Park K.: Effects of ethylene glycol-based graft, star-shaped, and den- dritic polymers on solubilization and controlled release of paclitaxel, J Control Release, 93,121-7. (2003)
  • Ozturk K, Caban S, Kozlu S, Kadayifci E, Yerlikaya F, Capan Y. The influence of tech- nological parameters on the physicochemical properties of blank PLGA nanoparticles, Pharmazie, 65,665-9. (2010)
  • Panchagnula R. Pharmaceutical aspects of paclitaxel, Int J Pharm, 1-15. (1998)
  • Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy, Nature Nanotech, 2,751 - 60. (2007)
  • Sharma A, Sharma US, Straubinger RM. Paclitaxel-liposomes for intracavitar therapy of intraperitoneal P388 leukemia, Cancer Lett, 107,265-72. (1996)
  • Songa KC, Lee HS, Chounga Y, In Choa K, Ahn Y, Choi EJ. The effect of type of organic phase solvents on the particle size of poly(d,l-lactide-co-glycolide) nanoparticles, Col- loid Surface A, 276,162–7. (2006)
  • Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices, J Control Release, 70,1-20. (2001)
  • Sparreboom A, Scripture CD, Trieu V, Williams PJ, De T, et al. Comparative preclini- cal and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol), Clin Cancer Res, 11,4136-43. (2005)
  • Twentyman PR, Luscombe M. A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity, Br J Cancer, 56,279-85. (1987)
  • Vicari L, Musumeci T, Giannone I, Adamo L, Conticello C, et al. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity, BMC Cancer, 8,212. (2008)
  • Yang Q, Owusu-Ababio G. Biodegradable progesteronemicrosphere delivery system for osteoporosis therapy, Drug Dev Ind Pharm, 26, 61–70. (2000)
  • Yerlikaya F, Ozgen A, Vural I, Guven O, Karaagaoglu E, Khan MA, Capan Y. Develop- ment and evaluation of paclitaxel nanoparticles using a quality-by-design approach, J Pharm Sci., 102, 3748-61. (2013)
  • Zambaux MF, Bonneaux F, Gref R, Maincent P, Dellacherie E, et al. Influence of experi- mental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method, J Control Release, 50,31-40. (1998)
  • Zhang L, He Y, Ma G, Song C, Sun H. Paclitaxel-loaded polymeric micelles based on poly(varepsilon-caprolactone)-poly(ethylene glycol)-poly(varepsilon-caprolactone) tri- block copolymers: in vitro and in vivo evaluation, Nanomedicine, 8,925-34. (2012)
There are 33 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Gözde Aygül This is me

Fırat Yerlikaya This is me

Secil Caban This is me

İmran Vural This is me

Yılmaz Çapan This is me

Publication Date January 1, 2013
Published in Issue Year 2013 Issue: 1

Cite

Vancouver Aygül G, Yerlikaya F, Caban S, Vural İ, Çapan Y. Formulation and in Vitro Evaluation of Paclitaxel Loaded Nanoparticles. HUJPHARM. 2013(1):25-40.