Volume : 09, Issue : 08, August – 2022

Title:

38.CHARACTERIZATION AND EVALUATION OF BIO-COMPATIBLE EUDRAGIT-S-100 NANOPARTICLE LOADED WITH CLOFARABINE AS POTENTIAL ANTI-TUMOR DRUG DELIVERY SYSTEM

Authors :

Bodige Mounika*, Tadaka Shirisha,N.Jhancy, Dr.N. Sandeepthi

Abstract :

Clofarabine is a second-generation purine nucleoside analog that has been synthesized to overcome the limitations and incorporate the best qualities of fludarabine and cladribine. Clofarabine acts by inhibiting ribonucleotide reductase and DNA polymerase, thereby depleting the amount of intracellular deoxynucleoside triphosphates available for DNA replication. Compared to its precursors, clofarabine has an increased resistance to deamination and phosphorolysis, and hence better stability as well as higher affinity to deoxycytidine kinase (dCyd), the rate-limiting step in nucleoside phosphorylation. Since the initiation of the first phase I study of clofarabine in 1993 in patients with hematologic and solid malignancies, clofarabine has demonstrated single-agent antitumor activity in adult acute leukemia, including acute myeloid leukemia (AML). Due to its unique properties of biochemical modulation when used in combination with other chemotherapy drugs, mainly cytarabine, combination regimens containing clofarabine have been evaluated. The treatment of acute leukaemias, which are the most common paediatric cancers, has improved considerably in recent decades, with complete response rates approaching ~90% in some cases. However, there remains a major need for treatments for patients who do not achieve or maintain complete remission, for whom the prognosis is very poor. In this article, we describe the challenges involved in the discovery and development of clofarabine, a second-generation nucleoside analogue that received accelerated approval from the US FDA at the end of 2004 for the treatment of paediatric patients 1–21 years old with relapsed or refractory acute lymphoblastic leukaemia after at least two prior regimens. It is the first such drug to be approved for paediatric leukaemia in more than a decade, and the first to receive approval for paediatric use before adult use.

Cite This Article:

Please cite this article in press Bodige Mounika et al, Characterization And Evaluation Of Bio-Compatible Eudragit-S-100 Nanoparticle Loaded With Clofarabine As Potential Anti-Tumor Drug Delivery System., Indo Am. J. P. Sci, 2022; 09(8).

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References:

1. Schiffer, C. A. Acute myeloid leukemia in adults: where do we go from here? Cancer Chemother. Pharmacol. 48 (Suppl.): S45–S52, 2001.
2. Plunkett, W., and Gandhi, V. Purine and pyrimidine nucleoside analogs. In: G.Giaccone, R. Schilsky, and P. Sondel (eds.), Cancer Chemotherapy and Biological Response Modifiers, Annual, Vol. 19, pp. 21–45. Amsterdam: Elsevier Science Publishers, B. V., 2001.
3. Gandhi, V., Plunkett, W., Du, M., Ayres, M., and Estey, E. Prolonged infusion of gemcitabine: clinical and pharmacodynamic studies during a Phase I trial in relapsed acute myelogenous leukemia. J. Clin. Oncol., 20: 665–673, 2002.
4. Silverman, L. R., Demakos, E. P., Bercedis, L., Kornblith, A. B., Holland, J. C., Odchimar-Reissig, R., Stone, R. M., Nelson, D., Powell, B. L., DeCastro, C. M.,et al. A randomized controlled trial of azacytidine in patients with myelodysplastic syndrome: a study of the cancer and leukemia group B. J. Clin. Oncol., 20: 2429–2440, 2002.
5. Wijermans, P., Lu ̈bbert, M., Verhoef, G., Bosly, A., Ravoet, C., Andre, M., Ferrant, A. Low-dose 5-aza-2-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter Phase II study in elderly patients. J. Clin. Oncol., 18: 956–962, 2000.
6. Piro, L. D., Carrera, C. J., Carson, D. A., and Beutler, E. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N.Engl. J. Med., 322: 1117–1121, 1990.
7. Montgomery, J. A., Shortnacy-Fowler, A. T., Clayton, S. D., Riordan, J. M., and Secrist, J. A., III. Synthesis and biologic activity of 2-fluoro-2-halo derivatives of
9. D-arabinofuranosyladenine. J. Med. Chem., 35: 397–401, 1992.
8. Parker, W. B., Allan, P. W., Hassan, A. E., Secrist, J. A., III, Sorscher, E. J., and Waud, W. R. Antitumor activity of 2-fluoro-2- deoxyadenosine against tumors that express Escherichia coli purine nucleoside phosphorylase. Cancer Gene Ther., 10: 23–29, 2003.
9. Carson, D. A., Wasson, D. B., Esparza, L. M., Carrera, C. J., Kipps, T. J., and Cottam, H. B. Oral antilymphocyte activity and induction of apoptosis by 2-chloro-2-arabino-fluoro-2deoxyadenosine. Proc. Natl. Acad. Sci. USA, 89: 2970–2974, 1992.
10. Parker, W. B., Shaddix, S. C., Rose, L. M., Shewach, D. S., Hertel, L. W., Secrist, J. A., III, Montgomery, J. A., and Bennett, L. L., Jr. Comparison of the mechanism of cytotoxicity of 2-chloro-9-(2-deoxy2-fluoro–D-arabinofuranosyl) adenine, 2-chloro-9-(2-deoxy-2-fluoro- -D-ribofuranosyl)adenine 2-chloro-9-(2-deoxy-2, 2-difluoro–D-ribofuranosyl)adenine in CEM cells. Mol. Pharmacol., 55:515–520, 1999.