Formulation And Optimization Of Lipid-Polymer Hybrid Nanoparticles For Targeted Delivery Of Docetaxel: A Novel Approach In Cancer Therapy
DOI:
https://doi.org/10.63682/jns.v14i32S.8836Keywords:
Docetaxel, Lipid-polymer hybrid nanoparticles, Targeted delivery, PLGA, Nanoprecipitation, Anticancer drug deliveryAbstract
Docetaxel, a potent chemotherapeutic agent, is widely used for the treatment of solid tumors such as breast, prostate, and lung cancer. However, its clinical use is limited by poor aqueous solubility, systemic toxicity, and multidrug resistance. The current study aimed to formulate and optimize lipid-polymer hybrid nanoparticles (LPHNs) of Docetaxel for improved tumor targeting, enhanced bioavailability, and reduced systemic side effects. LPHNs were prepared using the nanoprecipitation method combining PLGA (poly(lactic-co-glycolic acid)) as the polymeric core and lecithin/cholesterol as the lipid shell. A Box-Behnken design was employed to optimize the formulation parameters including lipid-to-polymer ratio, drug loading, and surfactant concentration. The optimized formulation exhibited a particle size of 145.3 ± 4.5 nm, PDI of 0.174, zeta potential of -22.6 ± 1.3 mV, and encapsulation efficiency of 89.6 ± 2.1%. In vitro drug release studies revealed a biphasic release profile with sustained release over 72 hours. Cytotoxicity studies on MCF-7 (breast cancer) cells showed significantly higher anticancer activity for LPHNs compared to free drug. These findings indicate that Docetaxel-loaded LPHNs offer a promising nanocarrier system for targeted cancer therapy
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World Health Organization. (2021). Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer
Danhier, F., Feron, O., & Préat, V. (2010). To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. Journal of Controlled Release, 148(2), 135–146. https://doi.org/10.1016/j.jconrel.2010.08.027
Baker, S. D., et al. (2004). Docetaxel-related toxicities: current management strategies. The Oncologist, 9(6), 556–564. https://doi.org/10.1634/theoncologist.9-6-556
de Sousa Cavalcante, L., & Monteiro, G. (2014). Docetaxel: a review of its pharmacology, efficacy and toxicity. Cancer Chemotherapy and Pharmacology, 73(5), 953–964. https://doi.org/10.1007/s00280-014-2400-5
Marupudi, N. I., et al. (2007). Taxanes: an update on new analogs, delivery strategies, and molecular targets. Cancer Chemotherapy and Pharmacology, 59(5), 531–552. https://doi.org/10.1007/s00280-006-0380-5
Clarke, S. J., et al. (1999). Hypersensitivity reactions to docetaxel: proposals for the use of premedication regimens. British Journal of Cancer, 81(5), 944–947. https://doi.org/10.1038/sj.bjc.6690799
Yadav, H. K. S., et al. (2020). Nanoparticles-based drug delivery systems for treatment of neurodegenerative diseases. Current Pharmaceutical Design, 26(25), 2976–2985. https://doi.org/10.2174/1381612826666200317145009
Torchilin, V. P. (2006). Multifunctional nanocarriers. Advanced Drug Delivery Reviews, 58(14), 1532–1555. https://doi.org/10.1016/j.addr.2006.09.009
Mitragotri, S., Burke, P. A., & Langer, R. (2014). Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nature Reviews Drug Discovery, 13(9), 655–672. https://doi.org/10.1038/nrd4363
Zhang, L., et al. (2008). Lipid–polymer hybrid nanoparticles: synthesis, characterization and applications. Nature Nanotechnology, 3(8), 443–448. https://doi.org/10.1038/nnano.2008.147
Khan, I., Saeed, K., & Khan, I. (2019). Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry, 12(7), 908–931. https://doi.org/10.1016/j.arabjc.2017.05.011
Yu, B., et al. (2012). Lipid-polymer hybrid nanoparticles for siRNA delivery: characterization and efficacy in cancer therapy. Biomaterials, 33(13), 4296–4305. https://doi.org/10.1016/j.biomaterials.2012.02.038
Xiong, M. H., et al. (2013). Nanoparticles for tumor-targeted delivery of anticancer drugs. Journal of Drug Targeting, 21(1), 1–26. https://doi.org/10.3109/1061186X.2012.716840Fessi, H., et al. (1989). Nanocapsule formation by interfacial polymer deposition following solvent displacement. International Journal of Pharmaceutics, 55(1), R1–R4.
Danaei, M., et al. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 10(2), 57. https://doi.org/10.3390/pharmaceutics10020057
Montgomery, D. C. (2017). Design and Analysis of Experiments. John Wiley & Sons.
Costa, C., et al. (2019). Optimization of nanoparticles using Box-Behnken design: a review. International Journal of Pharmaceutics, 566, 641–656. https://doi.org/10.1016/j.ijpharm.2019.06.024
Danaei, M., et al. (2021). The role of particle size on the cytotoxicity and cellular uptake of polymeric nanoparticles. Journal of Biomedical Materials Research Part A, 109(9), 1483–1495.
Honary, S., & Zahir, F. (2013). Effect of zeta potential on the properties of nano-drug delivery systems: a review. Tropical Journal of Pharmaceutical Research, 12(2), 255–264.
Duan, X., & Li, Y. (2013). Physicochemical characteristics of nanoparticles affecting their fate and biodistribution. Drug Delivery, 20(2), 63–73.
Ramasamy, T., et al. (2014). Design and evaluation of lipid–polymer hybrid nanoparticles for oral delivery of celecoxib: pharmacokinetic and pharmacodynamic studies. International Journal of Nanomedicine, 9, 63–76.
Bhatt, P., & Madhav, S. (2011). A detailed review on nanoemulsion drug delivery system. International Journal of Pharmaceutical Sciences and Research, 2(10), 2482–2489
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