FORMULATION AND OPTIMIZATION OF HYDROXYUREA LOADED NANOSTRUCTURED LIPID CARRIERS USING DESIGN OF EXPERIMENT FOR THE EFFECTIVE TREATMENT OF OVARIAN CANCER

Authors

  • PRAHARSH KUMAR MANDADHI RAJENDRA Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India
  • ANJALI PUTHUSSERIKKUNNU BALAN Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India https://orcid.org/0000-0002-6984-4346
  • JUBIE SELVARAJ Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India
  • NATARAJAN JAWAHAR Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India https://orcid.org/0000-0003-0737-1237

DOI:

https://doi.org/10.22159/ijap.2022v14i5.45464

Keywords:

Ovarian cancer, Hydroxyurea, Nanostructured lipid carriers, Optimization

Abstract

Objective: Ovarian cancer is the most deadly cancer in women, ranking fourth among all fatal diseases in women. Conventional chemotherapy has its own plethora of challenges, such as side effects and disease relapse. Hydroxyurea is a type of anticancer drug that is commonly used to treat malignancies. This study aims to develop and optimize hydroxyurea nanostructured lipid carriers (NLCs) to improve the therapeutic index and reduce its side effects in the effective treatment of OC.

Methods: NLCs were prepared by microemulsion technique. They were prepared and optimized using the design of experiment for particle size and drug entrapment efficiency. Particle size, polydispersity index, zeta potential, morphology, in vitro release, and stability were all examined in the optimized formulation.

Results: The results showed that the particle size of the NLCs was in the range of 224 nm to 634 nm. The drug entrapment efficiency of the NLCs was in the range of 46.33 % to 70.43 %. The optimized NLCs had a particle size of 237 nm, a polydispersity index of 26.9%, and a zeta potential of-29.7 mV. These NLCs were spherical, showed in vitro drug release of 92.21% up to 48 h, and were found to be stable from the stability studies.

Conclusion: This approach could be used as a better drug delivery platform to improve the drug's therapeutic index, reduce its side effects, and be feasible in the effective management of ovarian cancer.

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References

Wright AA, Cronin A, Milne DE, Bookman MA, Burger RA, Cohn DE. Use and effectiveness of intraperitoneal chemotherapy for treatment of ovarian cancer. J Clin Oncol. 2015 Sep 10;33(26):2841-7. doi: 10.1200/JCO.2015.61.4776, PMID 26240233.

Tewari D, Java JJ, Salani R, Armstrong DK, Markman M, Herzog T. Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2015 May 1;33(13):1460-6. doi: 10.1200/ JCO.2014.55.9898, PMID 25800756.

Jaaback K, Johnson N, Lawrie TA. Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev. 2016 Jan 12;2016(1):pub4:CD005340:CD005340. doi: 10.1002/14651858.CD005340.pub4.

Chandra A, Pius C, Nabeel M, Nair M, Vishwanatha JK, Ahmad S. Ovarian cancer: current status and strategies for improving therapeutic outcomes. Cancer Med. 2019 Nov;8(16):7018-31. doi: 10.1002/cam4.2560, PMID 31560828.

Pantshwa JM, Kondiah PPD, Choonara YE, Marimuthu T, Pillay V. Nanodrug delivery systems for the treatment of ovarian cancer. Cancers (Basel). 2020 Jan 15;12(1):213. doi: 10.3390/cancers12010213, PMID 31952210.

Napoletano C, Ruscito I, Bellati F, Zizzari IG, Rahimi H, Gasparri ML. Bevacizumab-based chemotherapy triggers immunological effects in responding to multi-treated recurrent ovarian cancer patients by favoring the recruitment of effector T cell subsets. J Clin Med. 2019 Mar 18;8(3):380. doi: 10.3390/jcm8030380, PMID 30889935.

Chishti N, Jagwani S, Dhamecha D, Jalalpure S, Dehghan MH. Preparation, optimization, and in vivo evaluation of nanoparticle-based formulation for pulmonary delivery of an anticancer drug. Medicina (Kaunas). 2019 Jun 20;55(6):294. doi: 10.3390/medicina55060294, PMID 31226865.

Azemati F, Jalali Kondori B, Esmaeili Gouvarchin Ghaleh H. Therapeutic potential of nanoparticle-loaded hydroxyurea on the proliferation of human breast adenocarcinoma cell line. Iran J Pharm Res. 2020;19(1):271-81. doi: 10.22037/ijpr.2020.1100921, PMID 32922486.

Thiele J, Kvasnicka HM, Schmitt Graeff A, Bundschuh S, Biermann T, Roessler G. Effects of chemotherapy (busulfan-hydroxyurea) and interferon-alfa on bone marrow morphologic features in chronic myelogenous leukemia. Histochemical and morphometric study on sequential trephine biopsy specimens with special emphasis on dynamic features. Am J Clin Pathol. 2000 Jul;114(1):57-65. doi: 10.1309/XMGX-7HQ8-7PLU-LQ9M, PMID 10884800.

Thang LQ, Hanh ND, Duong DQ. Study on cause-effect relations and optimization of exemestane-loaded nanostructured lipid carriers. Int J Pharm Pharm Sci. 2017 May;9(5):68-74. doi: 10.22159/ijpps.2017v9i5.17354.

Hashem F, Nasr M, Ahmed Y. Preparation and evaluation of iron oxide nanoparticles for treatment of iron deficiency anemia. Int J Pharm Pharm Sci. 2018 Jan 1;10(1):142-6. doi: 10.22159/ijpps.2018v10i1.22686.

Beloqui A, Solinis MA, Rodriguez Gascon A, Almeida AJ, Preat V. Nanostructured lipid carriers: promising drug delivery systems for future clinics. Nanomedicine. 2016 Jan;12(1):143-61. doi: 10.1016/j.nano.2015.09.004. PMID 26410277.

Awotwe Otoo D, Zidan AS, Rahman Z, Habib MJ. Evaluation of anticancer drug-loaded nanoparticle characteristics by nondestructive methodologies. AAPS PharmSciTech. 2012 Jun;13(2):611-22. doi: 10.1208/s12249-012-9782-7, PMID 22535519.

Sabzichi M, Mohammadian J, Yari Khosroushahi A, Bazzaz R, Hamishehkar H. Folate-targeted nanostructured lipid carriers (NLCs) enhance (letrozol) efficacy in MCF-7 breast cancer cells. Asian Pac J Cancer Prev. 2016 Dec 1;17(12):5185-8. doi: 10.22034/APJCP.2016.17.12.5185, PMID 28124885.

Shah J, Patel S, Bhairy S, Hirlekar R. Formulation optimization, characterization and in vitro anti-cancer activity of curcumin loaded nanostructured lipid carriers. Int J Curr Pharm Sci. 2022 Jan 15;14(1):31-43. doi: 10.22159/ijcpr.2022v14i1.44110.

Cirri M, Maestrini L, Maestrelli F, Mennini N, Mura P, Ghelardini C. Design, characterization and in vivo evaluation of nanostructured lipid carriers (NLC) as a new drug delivery system for oral hydrochlorothiazide administration in pediatric therapy. Drug Deliv. 2018 Nov;25(1):1910-21. doi: 10.1080/10717544.2018.1529209, PMID 30451015.

Xia D, Shrestha N, van de Streek J, Mu H, Yang M. Spray drying of fenofibrate loaded nanostructured lipid carriers. Asian J Pharm Sci. 2016;11(4):507-15. doi: 10.1016/ j.ajps.2016.01.001.

Noori Siahdasht F, Farhadian N, Karimi M, Hafizi L. Enhanced delivery of melatonin-loaded nanostructured lipid carriers during in vitro fertilization: NLC formulation, optimization and IVF efficacy. RSC Adv. 2020 Mar 4;10(16):9462-75. doi: 10.1039/c9ra10867j, PMID 35497203.

Wang H, Hong W, Li X, Jin Q, Ye W, Feng Y. Optimization of nanostructured lipid carriers of fenofibrate using a Box-Behnken design for oral bioavailability enhancement. Curr Drug Deliv. 2022;19(7):773-87. doi: 10.2174/ 1567201818666210423110745, PMID 33902411.

Natarajan J, Baskaran M, Humtsoe LC, Vadivelan R, Justin A. Enhanced brain targeting efficacy of olanzapine through solid lipid nanoparticles. Artif Cells Nanomed Biotechnol. 2017 Mar;45(2):364-71. doi: 10.3109/21691401.2016.1160402, PMID 27002542.

Asadi A. Streptomycin-loaded PLGA-alginate nanoparticles: preparation, characterization, and assessment. Appl Nanosci. 2014;4(4):455-60. doi: 10.1007/s13204-013-0219-8.

Seju U, Kumar A, Sawant KK. Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies. Acta Biomater. 2011 Dec;7(12):4169-76. doi: 10.1016/j.actbio.2011.07.025, PMID 21839863.

Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of state of the art. Eur J Pharm Biopharm. 2000 Jul;50(1):161-77. doi: 10.1016/s0939-6411(00)00087-4, PMID 10840199.

Huang W, Dou H, Wu H, Sun Z, Wang H, Huang L. Preparation and characterization of nobiletin-loaded nanostructured lipid carriers. J Nanomater. 2017 Jan 1;2017:1-10. doi: 10.1155/2017/2898342.

Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015 Sep;33(9):941-51. doi: 10.1038/nbt.3330, PMID 26348965.

Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001 May;13(2):123-33. doi: 10.1016/s0928-0987(01)00095-1, PMID 11297896.

Venkateswarlu V, Manjunath K. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J Control Release. 2004 Mar 24;95(3):627-38. doi: 10.1016/j.jconrel.2004.01.005. PMID 15023472.

Ye J, Wang Q, Zhou X, Zhang N. Injectable actarit-loaded solid lipid nanoparticles as passive targeting therapeutic agents for rheumatoid arthritis. Int J Pharm. 2008 Mar 20;352(1-2):273-9. doi: 10.1016/j.ijpharm.2007.10.014. PMID 18054182.

Yazdani Ashtiani S, Ahmad Nasrollahi S, Naeimifar A, Nassiri Kashani A, Samadi A, Yadangi S. Preparation and safety evaluation of topical simvastatin loaded NLCs for vitiligo. Adv Pharm Bull. 2021 Jan;11(1):104-10. doi: 10.34172/ apb.2021.011, PMID 33747857.

Published

07-09-2022

How to Cite

RAJENDRA, P. K. M., BALAN, A. P., SELVARAJ, J., & JAWAHAR, N. (2022). FORMULATION AND OPTIMIZATION OF HYDROXYUREA LOADED NANOSTRUCTURED LIPID CARRIERS USING DESIGN OF EXPERIMENT FOR THE EFFECTIVE TREATMENT OF OVARIAN CANCER. International Journal of Applied Pharmaceutics, 14(5), 137–143. https://doi.org/10.22159/ijap.2022v14i5.45464

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