Effects of nanocapsules containing all-trans-retinoic acid under hemolytic and coagulation activity

Keywords: Coagulation cascade, Hemolysis, Leukemia

Abstract

The chemotherapeutic all-trans retinoic acid (ATRA) used in the treatment of Acute Promyelocytic Leukemia has adverse effects on its oral administration, with which we incorporated a system of drugs, the nanocapsules, in order to have a possible improvement in solubility, photosensitivity, lower toxicity, generating pharmacological efficacy. The objective was to evaluate and compare the hemolytic and coagulation activity of the free drug (AL), nanoencapsulated (NA) and the white nanocapsules (NB) by analyzing the results of hemolysis, Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). We developed a prospective study of treatments at different concentrations of 0.25; 0.5; 1.0; 1.5; 2.0; 2.5 μg/mL. For the first test, all concentrations showed hemolytic activity, but when compared to NA with ATRA it is observed that these carriers induced lower hemolytic toxicity. In the PT test the nanoparticles at the two lowest concentrations remained in the physiological range (12 - 15 seconds). For the APTT test the three lowest concentrations remained within the control (25 - 35 seconds). Thus, we believe there is a promising benefit of using these nanoparticles developed and no doubt further studies will be performed to confirm the responses obtained here.

Downloads

Download data is not yet available.

Author Biography

Michele Rorato Sagrillo, Centro Universitário Franciscano/Docente

Centro de Ciências da Saúde - Curso de Biomedicina

Programa de Pós-Graduação em Nanociências

References

Craig SK, Barbara K, Craig MK. Consultative hemostasis and thrombosis. 2nd ed. Rio de Janeiro: Saunders; 2007.

Levi M, Ten CH. Disseminated intravascular coagulation. N Engl J Med. 1999; 341:586-92.

Asou N. All-trans retinoic acid in the treatment of acute promyelocytic leukemia. Intern Med. 2007; 46(2):91-3.

Marshall JC. Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit CareMed. 2001; 29:S99-106.

Fachinetto JM, Ourique AF, Lubini G, Tedesco SB, Silva ACF, Beck RCR. Tretinoin-loaded polymeric nanocapsules: evaluation of the potential to improve the antiproliferative activities on Allium ceparoot-tip compared to the free drug. Lat Am J Pharm. 2008; 27(5):668-73.

Ourique AF, Azoubel S, Ferreira CV, Silva CB, Marchiori MCL, Pohlmann AR, et al. Lipid-core nanocapsules as a nanomedicine for parenteral administration of tretinoin: development and in vitro antitumor activity on human myeloid leukaemia cells. J. Biomed. Nanotechnol. 2010; 6:214-23.

Fessi H, Puisieux F, Devissaguet JPh. Ammoury N, Benita S. Nanocapsule formation by interfacial Polymer deposition following solvent displacement. Internacional J pharm; 1989:R1-R4.

Dobrovolskaia MA, Patri AK, Zheng J, Clogston JD, Ayub N, Aggarwal P, et al. Interaction of colloidal gold nanoparticles with human blood: effects on particle size and analysis of plasma protein binding profiles. Nanomedicine; 2009; 5:106-17.

Salvador-Morales C, Zhang L, Langer R, Farokhzad OC. Immunocompatibility properties of lipid–polymer hybrid nanoparticles with heterogeneous surface functional groups. Biomaterials; 2009; 30:2231-40.

Adamson PC, Pitot HC, Balis FM, Rubin J, Murphy RF, Poplack DG. Variability in the oral bioavailability of all-trans-retinoic acid. J Natl Cancer Inst; 1993; 85(12):993-6.

Auffan M, Rose J, Bottero JY, Lowry GV, Jolivet JP, Wiesner MR. Toward a definition of inorganic nanoparticles from an enviromental, health and safety perspective. Nat Nanotechnol. 2009; 4.

Jácomo RH, Figueiredo-Pontes LL, Rego EM. From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukimia. Rev. Assoc. Med. Bras. 2008; 54(1):82-9.

Koziara JM, Oh JJ, Akers WS, Ferraris SP, Mumper RJ. Blood compatibility of cetyl alcohol/polysorbate-based nanoparticles. Pharm. Res. 2005; 22(11): 1821-28.

Tallman MS. Therapy of acute promyelocytic leukemia: all-trans retinoic acid and beyond. Leukemia; 1999; 12:37-40.

Ten CH, Timmerman JJ, Levi M. The pathophysiology of disseminated intravascular coagulation. Thromb Haemost. 1999; 82:713-7.

Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001; 86:1327-30.

Choudhry A, Deloughery TG. Bleeding and thrombosis in acute promyelocytic leukemia. Am J hematol. 2012; 87(6):596-603.

Lim SJ, Lee MK, Kim CK. Altered chemical and biological activities of all-trans retinoic acid incorporated in solid lipid nanoparticle powders. J Control Release. 2004; 100(1):53-61.

Hogan CJ, Wiley JS, Billington T. Intravascular haemolysis complicating treatment of acute promyelocytic leukaemia wih all-trans retinoic acid(ATRA). Aust. N.Z.J. Med. 1997; 27:450-1.

Sultana S, Khan MR, Kumar M, Kumar S, Ali M. Nanoparticles-mediated drug delivery approaches for cancer targeting: a review. J. Drug Target. 2012.

Hunt RL. Evaluation of the prothrombin time, a PTT, and platelet count in the bleeding infant. Neonatal Netw. 2011; 30:253-6.

Published
28-06-2019
How to Cite
Sousa Filho, W. P. de, Homrich, S. S., Copetti, P. M., Peres, D. S., Souza, D. V. de, Riéffel, R. C., Machado, A. K., Ourique, A. F., & Sagrillo, M. R. (2019). Effects of nanocapsules containing all-trans-retinoic acid under hemolytic and coagulation activity. Archives in Biosciences & Health, 1(1), 125-138. https://doi.org/10.18593/abh.16726
Section
Articles - Original research