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INVESTIGATION OF THE STABILIZATION OF CAMPTOTHECIN ANTICANCER DRUG VIA PSA-PEG POLYMERIC PARTICLES

Year 2016, Volume: 17 Issue: 1, 221 - 231, 25.04.2016
https://doi.org/10.18038/btda.87862

Abstract

Nano ve mikro taşıyıcı oluşumu için biyolojik olarak parçalanabilen PSA:PEG kopolimerlerinin sentezleri gerçekleştirilmiştir. Kamptotesin (CPT), antikanser ilaç olarak seçilmiştir. CPT fizyolojik koşullar altında kolay hidrolize olabilir (pH=7.4). Bu aktivite kaybına yol açar ve ilaç aktif lakton formundan aktif olmayan zehirli karboksilat forma dönüşür. Bu çalışmada anti kanser ilacı lakton formunda tutmak için, CPT etkili bir şekilde PSA:PEG nanopartikül ve mikropartiküllere yüklenmiştir ve taşıyıcı içindeki CPT kararlılığı detaylı bir şekilde HPLC ile incelenmiştir. Nano ve mikro taşıyıcılar içinde ilacın yüksek derecede kararlı ve aktif biçimde olduğu bulunmuştur (> % 95). Son olarak parçacıklar konfokal, SEM ve optik mikroskoplar ile görüntülenmiştir

References

  • Hou S, McCauley L K, Ma P X. Synthesis and erosion properties of PEG-containing Polyanhydrides. Macromol Biosci 2007; 7: 620–628.
  • Shuai X, Tan H. Synthesis and properties of biodegradable copolymers based on polyether oligomers and fatty diacids. J Appl Polym Sci 1997; 66: 1891–1898.
  • Domb A J, Langer R. Polyanhydrides. I. Preparation of high molecular weight polyanhydrides. J Polym Sci A1 1987; 25: 3373-3386.
  • Kumara N, Langer R S, Domb A J. Polyanhydrides: an overview. Adv Drug Deliver Rev 2002; 54: 889– 910.
  • Fu J, Fiegel J, Hanes J. Synthesis and characterization of PEG-based ether−anhydride terpolymers:  novel polymers for controlled drug delivery. Macromolecules 2004; 37: 7174-7180.
  • Fu J, Fiegel J, Krauland E, Hanes J, New polymeric carriers for controlled drug delivery following inhalation or injection. Biomaterials 2002; 23: 4425–4433.
  • Lee J, Joo M K, Oh H, Sohn Y S, Jeong B. Injectable gel: poly(ethylene glycol)-sebacic acid polyester. Polymer 2006; 47: 3760–3766.
  • Tang BC, Dawson M, Lai S K, Wang Y Y, Zeitlin P, Boyle M P, Fu J, Hanes J. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Pro Natl Acad Sci USA 2009; 106: 19268-73.
  • Tang B C, Fu J, Watkins D N, Hanes J, Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo. Biomaterials 2010; 31: 339–44.
  • Wall M E, Wani M C, Cook C E, Palmer K H, McPhail A T, Sim G A. Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from camptotheca acuminata. J Am Chem Soc 1966; 88: 3888-90.
  • Hsiang Y H, Hertzberg R, Hecht S, Liu L F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 1985; 260(27): 14873-14878.
  • Oberlies N H, Kroll D J, Camptothecin and taxol:  historic achievements in natural products research. J Nat Prod 2004; 67(2): 129-135.
  • Fassberg J, Stella V J, A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues. J Pharm Sci 1992; 81: 676-684.
  • Wani M C, Nicholas A W, Manikumar G, Wall M E. Plant antitumor agents. 25. Total synthesis and antileukemic activity of ring A substituted camptothecin analogs. structure-activity correlations. J Med Chem 1987; 30: 1774-1779.
  • Wani M C, Nicholas A W, Wall M E. Plant antitumor agents. 28. Resolution of a key tricyclic synthon, 5'(RS)-1,5-dioxo-5'-hydroxy-2'H,5'H,6'H-6'-oxopyrano[3',4'-f].delta.6,8-tetrahydroindolizine: total synthesis and antitumor activity of 20(S)- and 20(R)-camptothecin. J Med Chem 1987; 30: 2317-2319.
  • Jaxel C, Kohn K W, Wani M C, Wall M E. Pommier, Y. Structure-Activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res 1989; 49: 1465-1469.
  • Moertel C G, Schutt A J, Reitemeier R J, Hahn R G. Phase II study of camptothecin (NSC- 100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemoth Rep 1972; 56: 95-101.
  • Gottlieb J A, Luce J K. Treatment of malignant melanoma with camptothecin. Cancer Chemoth Rep 1972; 56: 103-105.
  • Dancey J, Eisenhauer E A. Current perspectives on camptothecins in cancer treatment. Br J Cancer 1996; 74: 327-338.
  • Pommier Y, Pourquier P, Fan Y, Strumberg D. Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme. Biochim Biophys Acta 1998; 1400: 83-106.
  • Shenderova A, Burke T G, Schwendeman S P. Stabilization of 10-Hydroxycamptothecin in poly(lactide-co-glycolide) microsphere delivery vehicles. Pharm Res 1997; 14: 1406-1414.
  • McCarron P A, Marouf W M, Quinn D J, Fay F, Burden R E, Olwill S A, Scott C J. Antibody targeting of camptothecin-loaded PLGA nanoparticles to tumor cells. Bioconjugate Chem 2008; 19: 1561-1569.
  • Tong R, Cheng J. Controlled Synthesis of Camptothecin−Polylactide Conjugates and Nanoconjugates. Bioconjugate Chem 2010; 21: 111-121.
  • Yang D, Strode J T, Spielmann H P, Wang A H-J, Burke T G. DNA Interactions of two clinical camptothecin drugs stabilize their active lactone forms. J Am Chem Soc 1998; 120: 2979-2980.
  • Liu J, Jiang Z, Zhang S, Saltzman W M. Poly(ω-pentadecalactone-co-butylene-co-succinate) nanoparticles as biodegradable carriers for camptothecin delivery. Biomaterials 2009; 30: 5707-5719.
  • Wani M C, Ronman P E, Lindley J T, Wall M E. Plant antitumor agents. 18. synthesis and biological activity of camptothecin analogs. J Med Chem 1980; 23: 554-560.
  • Mert O, Esendaglı G, Dogan A L, Demir A S. Injectable biodegradable polymeric system for preserving the active form and delayed-release of camptothecin anticancer drugs. RSC Adv 2012; 2: 176- 185.
  • Warner D L, Burke T G. Simple and versatile high-performance liquid chromatographic method for the simultaneous quantitation of the lactone and carboxylate forms of camptothecin anticancer drugs, J Chromatogr B Biomed Sci Appl 1997; 691: 161-171.

Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles

Year 2016, Volume: 17 Issue: 1, 221 - 231, 25.04.2016
https://doi.org/10.18038/btda.87862

Abstract

Syntheses of biodegradable PSA:PEG copolymers for the formation of nano and micro carriers were performed. Camptothecin (CPT) was selected as anti-cancer drug. CPT can easily hydrolyze at physiological conditions (pH=7.4). This causes the loss of its activity, and it turns into inactive toxic carboxylate form from active lactone state. To keep anti cancer drug in the lactone form, it was efficiently loaded into PSA:PEG nanoparticles and microparticles, and the stability of CPT in the carriers was fully examined with HPLC. It was found that the drug was highly stable and in active form in the prepared nano and microcarriers (>95 %). Particles were imaged with confocal, SEM, and optic microscopes.

References

  • Hou S, McCauley L K, Ma P X. Synthesis and erosion properties of PEG-containing Polyanhydrides. Macromol Biosci 2007; 7: 620–628.
  • Shuai X, Tan H. Synthesis and properties of biodegradable copolymers based on polyether oligomers and fatty diacids. J Appl Polym Sci 1997; 66: 1891–1898.
  • Domb A J, Langer R. Polyanhydrides. I. Preparation of high molecular weight polyanhydrides. J Polym Sci A1 1987; 25: 3373-3386.
  • Kumara N, Langer R S, Domb A J. Polyanhydrides: an overview. Adv Drug Deliver Rev 2002; 54: 889– 910.
  • Fu J, Fiegel J, Hanes J. Synthesis and characterization of PEG-based ether−anhydride terpolymers:  novel polymers for controlled drug delivery. Macromolecules 2004; 37: 7174-7180.
  • Fu J, Fiegel J, Krauland E, Hanes J, New polymeric carriers for controlled drug delivery following inhalation or injection. Biomaterials 2002; 23: 4425–4433.
  • Lee J, Joo M K, Oh H, Sohn Y S, Jeong B. Injectable gel: poly(ethylene glycol)-sebacic acid polyester. Polymer 2006; 47: 3760–3766.
  • Tang BC, Dawson M, Lai S K, Wang Y Y, Zeitlin P, Boyle M P, Fu J, Hanes J. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Pro Natl Acad Sci USA 2009; 106: 19268-73.
  • Tang B C, Fu J, Watkins D N, Hanes J, Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo. Biomaterials 2010; 31: 339–44.
  • Wall M E, Wani M C, Cook C E, Palmer K H, McPhail A T, Sim G A. Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from camptotheca acuminata. J Am Chem Soc 1966; 88: 3888-90.
  • Hsiang Y H, Hertzberg R, Hecht S, Liu L F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 1985; 260(27): 14873-14878.
  • Oberlies N H, Kroll D J, Camptothecin and taxol:  historic achievements in natural products research. J Nat Prod 2004; 67(2): 129-135.
  • Fassberg J, Stella V J, A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues. J Pharm Sci 1992; 81: 676-684.
  • Wani M C, Nicholas A W, Manikumar G, Wall M E. Plant antitumor agents. 25. Total synthesis and antileukemic activity of ring A substituted camptothecin analogs. structure-activity correlations. J Med Chem 1987; 30: 1774-1779.
  • Wani M C, Nicholas A W, Wall M E. Plant antitumor agents. 28. Resolution of a key tricyclic synthon, 5'(RS)-1,5-dioxo-5'-hydroxy-2'H,5'H,6'H-6'-oxopyrano[3',4'-f].delta.6,8-tetrahydroindolizine: total synthesis and antitumor activity of 20(S)- and 20(R)-camptothecin. J Med Chem 1987; 30: 2317-2319.
  • Jaxel C, Kohn K W, Wani M C, Wall M E. Pommier, Y. Structure-Activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res 1989; 49: 1465-1469.
  • Moertel C G, Schutt A J, Reitemeier R J, Hahn R G. Phase II study of camptothecin (NSC- 100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemoth Rep 1972; 56: 95-101.
  • Gottlieb J A, Luce J K. Treatment of malignant melanoma with camptothecin. Cancer Chemoth Rep 1972; 56: 103-105.
  • Dancey J, Eisenhauer E A. Current perspectives on camptothecins in cancer treatment. Br J Cancer 1996; 74: 327-338.
  • Pommier Y, Pourquier P, Fan Y, Strumberg D. Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme. Biochim Biophys Acta 1998; 1400: 83-106.
  • Shenderova A, Burke T G, Schwendeman S P. Stabilization of 10-Hydroxycamptothecin in poly(lactide-co-glycolide) microsphere delivery vehicles. Pharm Res 1997; 14: 1406-1414.
  • McCarron P A, Marouf W M, Quinn D J, Fay F, Burden R E, Olwill S A, Scott C J. Antibody targeting of camptothecin-loaded PLGA nanoparticles to tumor cells. Bioconjugate Chem 2008; 19: 1561-1569.
  • Tong R, Cheng J. Controlled Synthesis of Camptothecin−Polylactide Conjugates and Nanoconjugates. Bioconjugate Chem 2010; 21: 111-121.
  • Yang D, Strode J T, Spielmann H P, Wang A H-J, Burke T G. DNA Interactions of two clinical camptothecin drugs stabilize their active lactone forms. J Am Chem Soc 1998; 120: 2979-2980.
  • Liu J, Jiang Z, Zhang S, Saltzman W M. Poly(ω-pentadecalactone-co-butylene-co-succinate) nanoparticles as biodegradable carriers for camptothecin delivery. Biomaterials 2009; 30: 5707-5719.
  • Wani M C, Ronman P E, Lindley J T, Wall M E. Plant antitumor agents. 18. synthesis and biological activity of camptothecin analogs. J Med Chem 1980; 23: 554-560.
  • Mert O, Esendaglı G, Dogan A L, Demir A S. Injectable biodegradable polymeric system for preserving the active form and delayed-release of camptothecin anticancer drugs. RSC Adv 2012; 2: 176- 185.
  • Warner D L, Burke T G. Simple and versatile high-performance liquid chromatographic method for the simultaneous quantitation of the lactone and carboxylate forms of camptothecin anticancer drugs, J Chromatogr B Biomed Sci Appl 1997; 691: 161-171.
There are 28 citations in total.

Details

Journal Section Articles
Authors

Dilay Kizisar This is me

N. Tuna Subasi

Serap Eroksuz This is me

Ayhan S. Demir This is me

Olcay Mert

Publication Date April 25, 2016
Published in Issue Year 2016 Volume: 17 Issue: 1

Cite

APA Kizisar, D., Subasi, N. T., Eroksuz, S., Demir, A. S., et al. (2016). Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles. Anadolu University Journal of Science and Technology A - Applied Sciences and Engineering, 17(1), 221-231. https://doi.org/10.18038/btda.87862
AMA Kizisar D, Subasi NT, Eroksuz S, Demir AS, Mert O. Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles. AUJST-A. June 2016;17(1):221-231. doi:10.18038/btda.87862
Chicago Kizisar, Dilay, N. Tuna Subasi, Serap Eroksuz, Ayhan S. Demir, and Olcay Mert. “Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles”. Anadolu University Journal of Science and Technology A - Applied Sciences and Engineering 17, no. 1 (June 2016): 221-31. https://doi.org/10.18038/btda.87862.
EndNote Kizisar D, Subasi NT, Eroksuz S, Demir AS, Mert O (June 1, 2016) Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles. Anadolu University Journal of Science and Technology A - Applied Sciences and Engineering 17 1 221–231.
IEEE D. Kizisar, N. T. Subasi, S. Eroksuz, A. S. Demir, and O. Mert, “Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles”, AUJST-A, vol. 17, no. 1, pp. 221–231, 2016, doi: 10.18038/btda.87862.
ISNAD Kizisar, Dilay et al. “Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles”. Anadolu University Journal of Science and Technology A - Applied Sciences and Engineering 17/1 (June 2016), 221-231. https://doi.org/10.18038/btda.87862.
JAMA Kizisar D, Subasi NT, Eroksuz S, Demir AS, Mert O. Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles. AUJST-A. 2016;17:221–231.
MLA Kizisar, Dilay et al. “Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles”. Anadolu University Journal of Science and Technology A - Applied Sciences and Engineering, vol. 17, no. 1, 2016, pp. 221-3, doi:10.18038/btda.87862.
Vancouver Kizisar D, Subasi NT, Eroksuz S, Demir AS, Mert O. Investigation of The Stabilization of Camptothecin Anticancer Drug via PSA-PEG Polymeric Particles. AUJST-A. 2016;17(1):221-3.