CHITOSAN NANOBUBBLES DEVELOPMENT AND EVALUATION FOR THE DELIVERY OF SUNITINIB-AN ANTICANCER AGENT
DOI:
https://doi.org/10.22159/ijap.2022v14i6.45821Keywords:
Sunitinib, Anti-tumor agent, Chitosan shelled nanobubbles, Perfluoropentane, Definitive screening design (DSD)Abstract
Objective: In the current study, we introduced a novel method for creating Sunitinib nanobubbles by incorporating it into chitosan-shelled nanobubbles.
Methods: The Design Expert® programme randomly assigned around 13 experiments, and multiple regression analysis was used to statistically examine the data. The effect of the amount of sunitinib, amount of chitosan, amount of Epikuron 200, amount of palmitic acid and stirring speed, on percent encapsulation efficiency and drug load while maintain minimum particle size of nanobubbles as considered through a definitive screening plan. By placing limitations on the response parameters, the optimum formulation was created using a numerical optimization approach. The three improved formulations (Batch1 through Batch3) were assessed.
Results: The findings show that the nanobubbles particle size of 78.56-82.42 nm with an encapsulation efficiency of 68.48-69.56 % and loading capacity of 23.88-25.02%. The quantity of sunitinib released from nanobubbles was much larger (96.52 percent) than that from the sunitinib solution within 24 h, according to an in vitro release profile of the medication using ultrasonography. The hemolytic activity of the blank nanobubbles and sunitinib-loaded nanobubbles was measured to assess their safety up to a concentration of 10 mg/ml. With erythrocytes, drug-loaded nanobubbles had a good safety profile. FTIR, DSC studies indicated no chemical interactions, TEM images revealed nanobubbles size of 70-100 nm and stability studies shows no significant changes.
Conclusion: For contrast-enhanced tumour imaging and subsequent therapeutic administration, nanobubbles were found to be superior.
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Le Tourneau C, Raymond E, Faivre S. Sunitinib: a novel tyrosine kinase inhibitor. A brief review of its therapeutic potential in the treatment of renal carcinoma and gastrointestinal stromal tumors (GIST). Ther Clin Risk Manag. 2007 Jun;3(2):341-8. doi: 10.2147/tcrm.2007.3.2.341, PMID 18360643.
Kassem MG, Motiur Rahman AF, Korashy HM. Sunitinib malate. Profiles Drug Subst Excip Relat Methodol. 2012;37:363-88. doi: 10.1016/B978-0-12-397220-0.00009-X. PMID 22469323.
Ramazani F, Hiemstra C, Steendam R, Kazazi Hyseni F, Van Nostrum CF, Storm G. Sunitinib microspheres based on [PDLLA-PEG-PDLLA]-b-PLLA multi-block copolymers for ocular drug delivery. Eur J Pharm Biopharm. 2015 Sep 1;95(B):368-77. doi: 10.1016/j.ejpb.2015.02.011, PMID 25701807.
Joseph JJ, Sangeetha D, Gomathi T. Sunitinib loaded chitosan nanoparticles formulation and its evaluation. Int J Biol Macromol. 2016 Jan 1;82:952-8. doi: 10.1016/ j.ijbiomac.2015.10.079, PMID 26522243.
Nazari Vanani R, Azarpira N, Heli H, Karimian K, Sattarahmady N. A novel self-nano emulsifying formulation for sunitinib: evaluation of anticancer efficacy. Colloids Surf B Biointerfaces. 2017 Dec 1;160:65-72. doi: 10.1016/j.colsurfb.2017.09.008, PMID 28917151.
Leggio L, Arrabito G, Ferrara V, Vivarelli S, Paterno G, Marchetti B. Mastering the tools: natural versus artificial vesicles in nanomedicine. Adv Healthc Mater. 2020 Sep;9(18):e2000731. doi: 10.1002/adhm.202000731, PMID 32864899.
Bhowmik H, Nagasamy Venkatesh D, Kuila A, Kammari Harish Kumar N. A review. Int J Appl Pharm. 2018;10(4):207-1.
Zhang CB, Cao HL, Li Q, Tu J, Guo X, Liu Z. Enhancement effect of ultrasound-induced microbubble cavitation on branched polyethylenimine-mediated VEGF(165) transfection with varied N/P ratio. Ultrasound Med Biol. 2013;39(1):161-71. doi: 10.1016/j.ultrasmedbio.2012.08.025, PMID 23141903.
Van den Broek LA, Knoop RJ, Kappen FH, Boeriu CG. Chitosan films and blends for packaging material. Carbohydr Polym. 2015;116:237-42. doi: 10.1016/j.carbpol.2014.07.039, PMID 25458295.
Candioti LV, De Zan MM, Camara MS, Goicoechea HC. Experimental design and multiple response optimization. Using the desirability function in analytical methods development. Talanta. 2014 Jun 15;124:123-38. doi: 10.1016/ j.talanta.2014.01.034, PMID 24767454.
Cavalli R, Bisazza A, Trotta M, Argenziano M, Civra A, Donalisio M. New chitosan nanobubbles for ultrasound-mediated gene delivery: preparation and in vitro characterization. Int J Nanomedicine. 2012;7:3309-18. doi: 10.2147/IJN.S30912, PMID 22802689.
Babu Dr. Preparation, characterization and evaluation of chitosan nanobubbles for the targeted delivery of ibrutinib. Nat Phenom. 2021.
Alshetaili AS, Ansari MJ, Anwer MdK, Ganaie MA, Iqbal M, Alshahrani SM. Enhanced oral bioavailability of ibrutinib encapsulated poly (Lactic-co-glycolic acid) nanoparticles: pharmacokinetic evaluation in rats. Curr Pharm Anal. 2019;15(6):661-8. doi: 10.2174/1573412915666190314124932.
Hwang TL, Lin YK, Chi CH, Huang TH, Fang JY. Development and evaluation of perfluorocarbon nanobubbles for apomorphine delivery. J Pharm Sci. 2009;98(10):3735-47. doi: 10.1002/jps.21687, PMID 19156914.
Takano S, Kondo H. Quantitative method for determination of hemolytic activity of Clostridium septicum toxin. Japan J Med Sci Biol. 1987;40(2):47-59. doi: 10.7883/yoken1952.40.47, PMID 3430819.
Jones B, Nachtsheim CJ. A class of three-level designs for definitive screening in the presence of second-order effects. J Qual Technol. 2011 Jan 1;43(1):1-15. doi: 10.1080/ 00224065.2011.11917841.
Maherani B, Arab Tehrany E, Kheirolomoom A, Reshetov V, Stebe MJ, Linder M. Optimization and characterization of liposome formulation by mixture design. Analyst. 2012;137(3):773-86. doi: 10.1039/c1an15794a, PMID 22158519.
Derringer G, Suich R. Simultaneous optimization of several response variables. J Qual Technol. 1980 Oct 1;12(4):214-9. doi: 10.1080/00224065.1980.11980968.
Dhiman S, Verma S. Optimization of melt-in-mouth tablets of levocetirizine dihydrochloride using response surface methodology. Int J Pharm Pharm Sci. 2012;4.
Hoven VP, Tangpasuthadol V, Angkitpaiboon Y, Vallapa N, Kiatkamjornwong S. Surface-charged chitosan: preparation and protein adsorption. Carbohydr Polym. 2007 Mar 1;68(1):44-53. doi: 10.1016/j.carbpol.2006.07.008.
Natarajan, Satheesh, Rajan D, Prabakaran L, Meka Venkata, Perumal Chandran S. Formulation optimization, scale up technique and stability analysis of naproxen loaded lipospheres. Asian J Pharm Clin Res. 2014;7:121-6.
Manisha Bhoskar, Priyanka Patil. Development and evaluation of paclitaxel loaded nanoparticles using 24factorial design. Int J Curr Pharm Res. 2015;7(2):64-72.
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