Variables Affecting the Preparation and Characterization of Axitinib as Oral Niosmoes
DOI:
https://doi.org/10.31351/vol33iss3pp115-127Abstract
Axitinib is anticancer drug act on different solid tumors by inhibtion protein kinase enzyme which is responsible for support the tumors with blood demand. Due to its low solubility, it has low bioavailability when given orally also it is affected by liver metabolism. Axitinib formulated as non-ionic vesicles (niosomes) for the first time to study the effect of different variables on the in vitro behaviour of vesicles in a hope to improve drug oral bioavailability.
Niosomal dispersion formulas were formulated by diverse techniques via multiple kinds of surface-active agent (tween also span), cholesterol and dicetyl phosphate then evaluated for visual appearance, efficiency of drug entrapment (EE%), size of the vesicles, poly dispersity index, zetapotential, viscosity, invitro drug release and study the vesicles morphology by FE-SEM. Many variables effect on EE% were studied such as effect of surfactant amount and type, effect of surfactant combination, impact of various ratios of cholesterol, impact of DCP in various amount , effect of preparation method and effect of sonication time.
The results showed that the EE% between (50.97%-98.24%), the particle size was found within the range (64.5 nm - 530.79 nm), zeta potential which was between ( -16.6 to -31 mV), polydispersity index (PDI) <1 and viscosity between (584 – 889.6) centipoise. The niosomal dispersion F1 which contained 1:1 weight ratio (span60: cholesterol) was found with high EE% (96.5±0.16%), smallest particle size (64.5±0.5 nm), highest drug release (100%) of drug released at the end of 4 hours and FE-SEM photograph showed that niosomes were spherical with no aggregation and had a smooth surface.
The results showed that thin film hydration method with sonication for four minutes was the best method for preparation of axitinib niosomes, the type and amount of surfactants used, cholesterol ratio, stabilizer and the time of sonication had a substantial effect on EE%, the size of the vesicles as well as drug release; which were investigated so as to optimize the niosomal dispersion of anti-tumour drug reaching to an optimum formula that may improve drug bioavailability.
Key words: Axitinib, Anticancer, Vesicles, Surfactants, Invitro behaviour, Entrapment efficiency.
Received 21/6/2023
Accepted 12/9/2023
Published 15/9/2024
How to Cite
Publication Dates
References
Majidpoor J, Mortezaee K. Angiogenesis as a hallmark of solid tumors - clinical perspectives. Cell Oncol. 2021;44(4):715–37.
Lizárraga-Verdugo E, Avendaño-Félix M, Bermúdez M, Ramos-Payán R, Pérez-Plasencia C, Aguilar-Medina M. Cancer Stem Cells and Its Role in Angiogenesis and Vasculogenic Mimicry in Gastrointestinal Cancers. Front Oncol. 2020;10:1–8.
Paik ES, Kim TH, Cho YJ, Ryu J, Choi JJ, Lee YY, et al. Preclinical assessment of the VEGFR inhibitor axitinib as a therapeutic agent for epithelial ovarian cancer. Sci Rep. 2020;10(1):1–9.
Jiang H, Liao J, Wang L, Jin C, Mo J, Xiang S. The multikinase inhibitor axitinib in the treatment of advanced hepatocellular carcinoma: the current clinical applications and the molecular mechanisms. Front Immunol. 2023;14(May):1–11.
Meyo MT, Chen J, Goldwasser F, Hirsch L, Huillard O, Meyo MT, et al. A Profile of Avelumab Plus Axitinib in the Treatment of Renal Cell Carcinoma. Ther Clin Risk Manag. 2022;18(July):683–98.
Fink C, Sun D, Wagner K, Schneider M, Bauer H, Dolgos H, et al. Evaluating the sole of Solubility in oral absorption of poorly water-soluble drugs using physiologically-based pharmacokinetic modeling. Clin Pharmacol Ther. 2020;107(3):650–61.
Mahapatra APK, Patil V, Patil R. Solubility enhancement of poorly soluble drugs by using novel techniques : A comprehensive review. Int J PharmTech Res. 2020;13(2):80–93.
Mohamad EA, Fahmy HM. Niosomes and liposomes as promising carriers for dermal delivery of annona squamosa extract. Brazilian J Pharm Sci. 2020;56:1–8.
Momekova DB, Gugleva VE, Petrov PD. Nanoarchitectonics of multifunctional niosomes for advanced drug delivery. ACS Omega. 2021;6(49):33265–73.
1Aboubakr EM, Mohammed HA, Hassan AS, Mohamed HB, El Dosoky MI, Ahmad AM. Glutathione-loaded non-ionic surfactant niosomes: A new approach to improve oral bioavailability and hepatoprotective efficacy of glutathione. Nanotechnol Rev. 2021;11(1):117–37.
Arzani G, Haeri A, Daeihamed M, Bakhtiari-Kaboutaraki H, Dadashzadeh S. Niosomal carriers enhance oral bioavailability of carvedilol: Effects of bile salt-enriched vesicles and carrier surface charge. Int J Nanomedicine. 2015;10:4797–813.
Mohsen AM, AbouSamra MM, ElShebiney SA. Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation. Drug Dev Ind Pharm. 2017;43(8):1254–64.
Khan DH, Bashir S, Khan MI, Figueiredo P, Santos HA, Peltonen L. Formulation optimization and in vitro characterization of rifampicin and ceftriaxone dual drug loaded niosomes with high energy probe sonication technique. J Drug Deliv Sci Technol. 2020;58:101763.
Wang Z, Liu L, Xiang S, Jiang C, Wu W, Ruan S, et al. Formulation and Characterization of a 3D-Printed Cryptotanshinone-Loaded Niosomal Hydrogel for Topical Therapy of Acne. AAPS PharmSciTech. 2020;21(5):1–13.
Rupali S, Anupama D, Satish S, Shekhar S, Amisha V. Development and Evaluation of Niosomal Gel for TransdermalApplication of steroidal API. Int Res J Adv Sci Hub. 2020;2(8):1–18.
Ruckmani K, Sankar V. Formulation and optimization of zidovudine niosomes. AAPS PharmSciTech. 2010;11(3):1119–27.
Maraie NK, Neamah MJ. A newly modified HPLC method for estimation of dutasteride in prepared niosomes. Al Mustansiriyah J Pharm Sci. 2017;17(2):104–11.
Ghafelehbashi R, Akbarzadeh I, Tavakkoli Yaraki M, Lajevardi A, Fatemizadeh M, Heidarpoor Saremi L. Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes. Int J Pharm. 2019;569:118580.
Sankhyan A, Pawar PK. Metformin loaded non-ionic surfactant vesicles: Optimization of formulation, effect of process variables and characterization. DARU, J Pharm Sci. 2013;21(1):1–8.
Junyaprasert VB, Singhsa P, Suksiriworapong J, Chantasart D. Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of ellagic acid. Int J Pharm. 2012;423(2):303–11.
Kamali M, Noori A, Soufdoost RS. N-acetyl cysteine loaded-niosomes as a mucolytic agent for acute diseases and respiratory disorders. Biointerface Res Appl Chem. 2021;11(2):8957–68.
Mohamed MI, Kassem MA, Khalil RM, Younis MM, Darwish AB, Salama A, et al. Enhancement of the anti-inflammatory efficacy of betamethasone valerate via niosomal encapsulation. Biointerface Res Appl Chem. 2021;11(6):14640–60.
Etal L key yoe. effect of preparation methods on characteristics of niosomes. Br J Pharm. 2019;1(4):24–5.
Psimadas D, Georgoulias P, Valotassiou V, Loudos G. Molecular Nanomedicine Towards Cancer : J Pharm Sci. 2012;101(7):2271–80.
Nizamudeen ZA, Xerri R, Parmenter C, Suain K, Markus R, Chakrabarti L, et al. Low-Power Sonication Can Alter Extracellular Vesicle Size and Properties. cells J. 2021;10(2413):1–13.
Hardia A, Jamindar D, Mahajan A, Hardia A, Pradesh M. Formulation And In Vitro And Skin Permeability Evaluation of Dexamethasone Loaded Niosomal Gel. Asian J Pharm Res Dev. 2017;5(2):1–9.
Maraie NK, Neamah MJ. Application of proniosomal powder technology to prepare fast water dissolving tablets for dutasteride. J Glob Pharma Technol. 2018;10(3):916–27.
Rehman MU, Rasul A, Khan MI, Rasool M, Abbas G, Masood F, et al. Oral bioavailability studies of niosomal formulations of Cyclosporine A in albino rabbits. Pak J Pharm Sci. 2021;34(1):313–9.
Abbas MM, Rajab NA. Preparation and characterization of etodolac as a topical nanosponges hydrogel. Iraqi J Pharm Sci. 2019;28(1):64–74.
Abdelkader H, Wu Z, Al-Kassas R, Alany RG. Niosomes and discomes for ocular delivery of naltrexone hydrochloride: Morphological, rheological, spreading properties and photo-protective effects. Int J Pharm. 2012;433(1–2):142–8.
Hashim AA, Rajab NA. Anastrozole Loaded Nanostructured Lipid Carriers: Preparation and Evaluation. Iraqi J Pharm Sci. 2021;30(2):185–95.
Rasul A, Khan MI, Rehman MU, Abbas G, Aslam N, Ahmad S, et al. In vitro characterization and release studies of combined nonionic surfactant-based vesicles for the prolonged delivery of an immunosuppressant model drug. Int J Nanomedicine. 2020;15:7937–49.
Noor AH, Ghareeb MM. Formulation and evaluation of ondansetron HCl nanoparticles for transdermal delivery. Iraqi J Pharm Sci. 2020;29(2):70–9.
Sabry S, El hakim Ramadan A, Abd elghany M, Okda T, Hasan A. Formulation, characterization, and evaluation of the anti-tumor activity of nanosized galangin loaded niosomes on chemically induced hepatocellular carcinoma in rats. J Drug Deliv Sci Technol. 2021;61:102163.
Damera DP, Venuganti VVK, Nag A. Deciphering the Role of Bilayer of a Niosome towards Controlling the Entrapment and Release of Dyes. ChemistrySelect. 2018;3(14):3930–8.
Academy P, Rajput L, Pradesh U. To Investigate the Effect of Span 60 and Span 80 Polymer on Release Rate of Simvastatin Noisome in Comparison With Pure Simvastatin. Int J Pharm Sci Res. 2021;12(7):3799–804.
Sternberg B, Florence AT. Preparation and properties of vesicles ( niosomes ) and a sorbitan triester ( Span 85 ). Int J Pharm. 1994;105:1–6.
Chen S, Hanning S, Falconer J, Locke M, Wen J. Recent advances in non-ionic surfactant vesicles (niosomes): Fabrication, characterization, pharmaceutical and cosmetic applications. Eur J Pharm Biopharm. 2019;144:18–39.
Gharbavi M, Amani J, Kheiri-Manjili H, Danafar H, Sharafi A. Niosome: A Promising Nanocarrier for Natural Drug Delivery through Blood-Brain Barrier. Adv Pharmacol Sci. 2018;1–15.
Thabet Y, Elsabahy M, Eissa NG. Methods for preparation of niosomes: A focus on thin-film hydration method. Methods. 2022;199(2021):9–15.
Pardakhty A, Shakibaie M, Daneshvar H, Khamesipour A, Mohammadi-Khorsand T, Forootanfar H. Preparation and evaluation of niosomes containing autoclaved Leishmania major: A preliminary study. J Microencapsul. 2012;29(3):219–24.
Aboud HM, Ali AA, El-Menshawe SF, Elbary AA. Nanotransfersomes of carvedilol for intranasal delivery: formulation, characterization and in vivo evaluation. Drug Deliv. 2016;23(7):2471–81.
Arafa MG, Ayoub BM. DOE Optimization of Nano-based Carrier of Pregabalin as Hydrogel: New Therapeutic &chemometric Approaches for Controlled Drug Delivery Systems. Sci Rep. 2017;7:1–15.
Gulati, M., Grover, M., Singh, S., Singh M. Lipophilic drug derivatives in liposomes. Int J Pharm. 1998;165:129–68.
Pando D, Gutiérrez G, Coca J, Pazos C. Preparation and characterization of niosomes containing resveratrol. J Food Eng. 2013;117(2):227–34.
Ekambaram P, Abdul Hasan Sathali A. Formulation and evaluation of solid lipid nanoparticles of ramipril. J Young Pharm. 2011;3(3):216–20.
Fang JY, Yu SY, Wu PC et al. In vitro skin permeation of estradiol from various proniosome formulations. Int J Pharm. 2001;215:91–9.
Taymouri S, Varshosaz J. Effect of different types of surfactants on the physical properties and stability of carvedilol nano-niosomes. Adv Biomed Res. 2016;5(1):48.
Bala I, Bhardwaj V, Hariharan S, Kumar MNVR. Analytical methods for assay of ellagic acid and its solubility studies. J Pharm Biomed Anal. 2006;40(1):206–10.
Palozza P, Muzzalupo R, Trombino S, Valdannini A, Picci N. Solubilization and stabilization of β-carotene in niosomes: Delivery to cultured cells. Chem Phys Lipids. 2006;139(1):32–42.
Shilakari Asthana G, Asthana A, Singh D, Sharma PK. Etodolac Containing Topical Niosomal Gel: Formulation Development and Evaluation. J Drug Deliv. 2016;1–8.
Asthana GS, Sharma PK, Asthana A. In Vitro and in Vivo Evaluation of Niosomal Formulation for Controlled Delivery of Clarithromycin. Scientifica (Cairo). 2016;1–10.
Hnin HM, Stefánsson E, Loftsson T, Asasutjarit R, Charnvanich D, Jansook P. Physicochemical and Stability Evaluation of Topical Niosomal Encapsulating Fosinopril/γ-Cyclodextrin Complex for Ocular Delivery. Pharmaceutics. 2022;14(6):2–16.
Basiri L, Rajabzadeh G, Bostan A. Physicochemical properties and release behavior of Span 60/Tween 60 niosomes as vehicle for α-Tocopherol delivery. LWT - Food Sci Technol. 2017;84:471–8.
Gharbavi M, Amani J, Kheiri-Manjili H, Danafar H, Sharafi A. Niosome: A Promising Nanocarrier for Natural Drug Delivery through Blood-Brain Barrier. Adv Pharmacol Sci. 2018;2018:1–15.
El-Nesr OH, Yahiya SA, El-Gazayerly ON. Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes. Saudi Pharm J. 2010;18(4):217–24.
Mokhtar M, Sammour OA, Hammad MA, Megrab NA. Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes. Int J Pharm. 2008;361(1–2):104–11.
Tagrida M, Prodpran T, Zhang B, Aluko RE, Benjakul S. Liposomes loaded with betel leaf (Piper betle L.) ethanolic extract prepared by thin film hydration and ethanol injection methods: Characteristics and antioxidant activities. J Food Biochem. 2021;45(12).
Neamah WF, Maraie NK. Factors affecting preparation and evaluation of Kitorolac tromethamine microsponges for ocular use. Al Mustansiriyah J Pharm Sci. 2020;20(3):58–70.
Khan DH, Bashir S, Figueiredo P, Santos HA, Khan MI, Peltonen L. Process optimization of ecological probe sonication technique for production of rifampicin loaded niosomes. J Drug Deliv Sci Technol. 2019;50(2018):27–33.
Nowroozi F, Almasi A, Javidi J, Haeri A, Dadashzadeh S. Effect of surfactant type, cholesterol content and various downsizing methods on the particle size of niosomes. Iran J Pharm Res. 2018 Sep 1;17(2):1–11.
He Y, Luo L, Liang S, Long M, Xu H. Influence of probe-sonication process on drug entrapment efficiency of liposomes loaded with a hydrophobic drug. Int J Polym Mater Polym Biomater. 2019;68(4):193–7.
Jawad AQ, Maraie NK. Preparation and Evaluation of a Sustained Release Niosomal Dispersion Containing Niflumic Acid. Int J Drug Deliv Technol. 2022;12(3):1105–11.
Das MK, Palei NN. Sorbitan ester niosomes for topical delivery of rofecoxib. Indian J Exp Biol. 2011;49(6):438–45.
Nekkanti V, Vabalaboina V, Pillai R. Drug Nanoparticles - An Overview. Deliv Nanoparticles. 2012;111–32.
Sarheed O, Dibi M, Ramesh KVRNS. Studies on the effect of oil and surfactant on the formation of alginate-based O/W lidocaine nanocarriers using nanoemulsion template. Pharmaceutics. 2020;12(12):1–21.
Ray S, Mishra A, Mandal TK, Sa B, Chakraborty J. Optimization of the process parameters for the fabrication of a polymer coated layered double hydroxide-methotrexate nanohybrid for the possible treatment of osteosarcoma. J RSC Adv. 2015;5(124):102574–92.
Alkwak RSY, Rajab NA. Lornoxicam-Loaded Cubosomes : - Preparation and In vitro Characterization. Iraqi J Pharm Sci. 2022;31(1):144–53.
Witika BA, Bassey KE, Demana PH, Siwe-Noundou X, Poka MS. Current Advances in Specialised Niosomal Drug Delivery: Manufacture, Characterization and Drug Delivery Applications. Int J Mol Sci. 2022;23(17):2–26.
Khademi M, Wang W, Reitinger W, Barz DPJ. Zeta Potential of Poly(methyl methacrylate) (PMMA) in Contact with Aqueous Electrolyte-Surfactant Solutions. Langmuir. 2017;33(40):10473–82.
Ibrahim MMA, Sammour OA, Hammad MA, Megrab NA. In vitro evaluation of proniosomes as a drug carrier for flurbiprofen. AAPS PharmSciTech. 2008;9(3):782–90.
Akbari V, Abedi D, Pardakhty A, Sadeghi-Aliabadi H. Release studies on ciprofloxacin loaded non-ionic surfactant vesicles. Avicenna J Med Biotechnol. 2015;7(2):69–75.
Keservani RK, Gautam SP. Skeletal muscle relaxant activity of different formulation of span 60 niosomes. Ars Pharm. 2021;63(1):32–44.
Hasan AA, Madkor H, Wageh S. Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system. J Drug Deliv. 2013;7544:120–6.
Kamboj S, Saini V, Bala S. Formulation and characterization of drug loaded nonionic surfactant vesicles (Niosomes) for oral bioavailability enhancement. Sci World J. 2014;1–8.
Hemati M, Haghiralsadat F, Yazdian F, Jafari F, Moradi A, Malekpour-Dehkordi Z. Development and characterization of a novel cationic PEGylated niosome-encapsulated forms of doxorubicin, quercetin and siRNA for the treatment of cancer by using combination therapy. Artif Cells, Nanomedicine Biotechnol. 2019;47(1):1295–311.
Elfadl AA, Boughdady M, Meshali M. New peceolTM/spanTM 60 niosomes coated with chitosan for candesartan cilexetil: Perspective increase in absolute bioavailability in rats. Int J Nanomedicine. 2021;16:5581–601.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Iraqi Journal of Pharmaceutical Sciences( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512)
This work is licensed under a Creative Commons Attribution 4.0 International License.
