Design, Development and Characterization of Nanostructure Lipid Carriers (NLCs) by HPH Method Loaded with Anticancer Drug
The Nanostructured Lipid Carriers (NLCs) was formulated with the aim to improve the aqueous solubility and thus ultimately oral bioavailability of Axitinib. Axitinib loaded NLCs were formulated using Compritol ATO 888 as solid-lipid, Oleic acid as liquid-lipid and Tween 80 as surfactant by the High-Pressure Homogenization technique. A full 23 factorial design was utilized to study the effect of the independent parameters, solid-lipid to the liquid-lipid ratio (6:4) and surfactant, on the dependent variables such as Mean Particle Size (MPS) and Entrapment Efficiency (%EE). Optimized formulation showed 202.2 nm MPS, -21.5 mV zeta-potential and 0.44 PDI, and 88% EE, which imparts good stability of developed NLCs. The physicochemical characterization of AXT loaded NLCs was done by examining the results of Differential Scanning Calorimetry, Fourier transform infrared spectroscopy study. The stability study of optimized formulation was found to be stable with no significant change in particle size, and drug content. In vitro release profiles of NLCs indicated a burst release for the first 2 hrs followed by a prolonged-release profile for AXT until about more than 10 hrs. The Axitinib NLCs may provide a better bioavailability, reduction in dose, dosing frequency, dose-related side effects and better control of the disease. A foresaid results showed the potential of NLCs for significant improvement in oral bioavailability of poorly soluble Axitinib in cancer treatment.
Keywords: NLCs, full factorial design, high-pressure homogenization, in-vitro release
2. Petejova N, Martinek A, Renal cell carcinoma: Review of etiology, pathophysiology and risk factors. Biomedical Papers, 2016; 160(2):183-194. https://doi.org/10.5507/bp.2015.050
3. Nabi S, Kessler ER, Bernard B, Flaig TW, Lam ET. Renal cell carcinoma: a review of biology and pathophysiology. F1000Research, 2018; 7:307. https://doi.org/10.12688/f1000research.13179.1
4. Choi JY, Ramasamy T, Kim SY, Kim J, Ku SK, Youn YS, Kim JR, Jeong JH, Choi HG, Yong CS, Kim JO, PEGylated lipid bilayer-supported mesoporous silica nanoparticle composite for synergistic co-delivery of axitinib and celastrol in multi-targeted cancer therapy, Acta Biomaterialia, 2016; 39:94-105. https://doi.org/10.1016/j.actbio.2016.05.012
5. Sonpavde G, Hutson TE, Rini BI, Axitinib for renal cell carcinoma. Expert Opinion on Investigational Drugs, 2008; 17(5):741-748. https://doi.org/10.1517/13543718.104.22.1681
6. Narayan, V., & Haas, N. B. Axitinib in the treatment of renal cell carcinoma: Patient selection and perspectives. International Journal of Nephrology and Renovascular Disease, 2016; 9:65-72. https://doi.org/10.2147/IJNRD.S83874
7. Akaza H, Fukuyama T, Axitinib for the treatment of advanced renal cell carcinom, Expert Opinion, 2014; 15(2):283-297. https://doi.org/10.1517/14656566.2014.868436
8. Yu G, Ali Z, Khan AS, Ullah K, Jamshaid H, Zeb A, Imran M, Sarwar S, Choi H G, Ud DinF, Preparation, pharmacokinetics, and antitumor potential of miltefosine-loaded nanostructured lipid carriers. International Journal of Nanomedicine, 2021;16:3255-3273. https://doi.org/10.2147/IJN.S299443
9. Beloqui A, Solinís MÁ, Rodríguez-Gascón A, Almeida AJ, Préat V, Nanostructured lipid carriers: Promising drug delivery systems for future clinics, Nanomedicine: Nanotechnology, Biology, and Medicine, 2016; 12(1):143-161. https://doi.org/10.1016/j.nano.2015.09.004
10. Nagaich U, Gulati N, Nanostructured lipid carriers (NLC) based controlled release topical gel of clobetasol propionate: design and in vivo characterization. Drug Delivery and Translational Research, 2016; 6(3):289-298. https://doi.org/10.1007/s13346-016-0291-1
11. Tamjidi F, Shahedi M, Varshosaz J, Nasirpour A, Design and characterization of astaxanthin-loaded nanostructured lipid carriers. Innovative Food Science and Emerging Technologies, 2014; 26:366-374. https://doi.org/10.1016/j.ifset.2014.06.012
12. Thakkar HP, Desai JL, Parmar MP, Application of Box-Behnken design for optimization of formulation parameters for nanostructured lipid carriers of candesartan cilexetil. Asian Journal of Pharmaceutics, 2014; 8(2):81-89. https://doi.org/10.4103/0973-8398.134921
13. Araújo J, Gonzalez-Mira E, Egea MA, Garcia ML, Souto EB, Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications, International Journal of Pharmaceutics, 2010; 393(1-2):168-176. https://doi.org/10.1016/j.ijpharm.2010.03.034
14. Chalikwar SS, Belgamwar VS, Talele VR, Surana SJ, Patil MU, Formulation and evaluation of Nimodipine-loaded solid lipid nanoparticles delivered via lymphatic transport system. Colloids and Surfaces B: Biointerfaces, 2012; 97:109-116. https://doi.org/10.1016/j.colsurfb.2012.04.027
15. Obeidat WM, Schwabe K, Müller RH, Keck CM, Preservation of nanostructured lipid carriers (NLC). European Journal of Pharmaceutics and Biopharmaceutics, 2010; 76(1):56-67. https://doi.org/10.1016/j.ejpb.2010.05.001
16. Varshosaz J, Ghaffari S, Khoshayand MR, Atyabi F, Azarmi S, Kobarfard F, Development and optimization of solid lipid nanoparticles of amikacin by central composite design. Journal of Liposome Research, 2010; 20(2):97-104. https://doi.org/10.3109/08982100903103904
17. Panda C, Chauhan SP, Balamurugan K, Formulation and in vitro characterization of raloxifene nanostructured lipid carriers for oral delivery with full factorial design-based studies using quality by design (Qbd) approach. International Journal of Research in Pharmaceutical Sciences, 2020; 11(4):6417-6427. https://doi.org/10.26452/ijrps.v11i4.3434
18. Jores K, Mehnert W, Drechsler M, Bunjes H, Johann C, Mäder K, Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. Journal of Controlled Release, 2004; 95(2):217-227. https://doi.org/10.1016/j.jconrel.2003.11.012
19. Serpe L, Catalano MG, Cavalli R, Ugazio E, Bosco O, Canaparo R, Muntoni E, Frairia R, Gasco MR, Eandi M, Zara GP, Cytotoxicity of anticancer drugs incorporated in solid lipid nanoparticles on HT-29 colorectal cancer cell line. European Journal of Pharmaceutics and Biopharmaceutics, 2004; 58(3):673-680. https://doi.org/10.1016/j.ejpb.2004.03.026
20. Dudhipala N, Veerabrahma K, Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. Drug Development and Industrial Pharmacy, 2015; 41(12):1968-1977. https://doi.org/10.3109/03639045.2015.1024685
21. Mathur P, Sharma S, Rawal S, Patel B, Patel MM, Fabrication, optimization, and in vitro evaluation of docetaxel-loaded nanostructured lipid carriers for improved anticancer activity. Journal of Liposome Research, 2020; 30(2):182-196. https://doi.org/10.1080/08982104.2019.1614055
22. Dangre PV, Godbole MD, Ingale PV, Mahapatra DK, Improved dissolution and bioavailability of eprosartan mesylate formulated as solid dispersions using conventional methods. Indian Journal of Pharmaceutical Education and Research, 2016; 50(3):S209-S217. https://doi.org/10.5530/ijper.50.3.31
23. Chen ND, Chen NF, Li J, Cao CY, Wang JM, Rapid authentication of different ages of tissue-cultured and wild Dendrobium huoshanense as well as wild Dendrobium henanense using FTIR and 2D-COS IR. Journal of Molecular Structure, 2015; 1101:101-108. https://doi.org/10.1016/j.molstruc.2015.08.011
24. Wang W, Chen L, Huang X, Shao A, Preparation and Characterization of Minoxidil Loaded Nanostructured Lipid Carriers. AAPS PharmSciTech, 2017; 18(2):509-516. https://doi.org/10.1208/s12249-016-0519-x
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).