Exploring an interesting dual functionality of anacardic acid for efficient paclitaxel delivery in breast cancer therapy
Abstract
Aim: To explore the potential of paclitaxel (PTX)-loaded anacardic acid conjugated hydrophobized gelatin nanoparticles. Materials & methods: Nanoparticles prepared by nanoprecipitation technique were evaluated for various quality attributes (particle size, % entrapment efficiency) in vitro drug release, MCF-7 cell uptake, cell cytotoxicity, in vivo pharmacokinetics, antitumor efficacy and toxicity. Results: The nanoparticles (250–300 nm, 74% entrapment efficiency) showed approximately 2.26-fold higher apoptosis index and approximately 5.86-fold reduction in IC50 value compared with PTX in MCF-7 cells. Also, approximately 3.51- and 1.36-fold increase in area under the curve compared with Intaxel® and Nanoxel™ (both from Fresenius Kabi, Gurugram, India) was achieved. Significant tumor burden reduction (∼60%) and reduced toxicity was observed compared with marketed formulations. Conclusion: The hydrophobized gelatin nanoparticles displayed promising therapeutic potential, paving a new path for efficient PTX delivery.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1 . Hyaluronan oligomers-HPMA copolymer conjugates for targeting paclitaxel to CD44-overexpressing ovarian carcinoma. Pharm. Res. 29(4), 1121–1133 (2012).
- 2 Overview of taxol safety. J. Natl Cancer Inst. Monogr. (15), 131–139 (1993).
- 3 Hypersensitivity reactions from taxol. J. Clin. Oncol. 8(7), 1263–1268 (1990).
- 4 . Paclitaxel and its formulations. Int. J. Pharm. 235(1), 179–192 (2002). • The hurdles and challenges of the current marketed paclitaxel formulations are highlighted.
- 5 . Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur. J. Cancer 37(13), 1590–1598 (2001). • The problems associated with the current solvent system employed for paclitaxel formulation are highlighted.
- 6 . BCS class IV drugs: highly notorious candidates for formulation development. J. Control. Rel. 248, 71–95 (2017).
- 7 Anti-tumor activity of paclitaxel-loaded chitosan nanoparticles: an in vitro study. Mater. Sci. Eng. C. 29(8), 2392–2397 (2009).
- 8 Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel. J. Control. Rel. 111(1), 228–234 (2006).
- 9 . Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J. Control. Rel. 83(2), 273–286 (2002).
- 10 . A novel controlled release formulation for the anticancer drug paclitaxel (Taxol®): PLGA nanoparticles containing vitamin E TPGS. J. Control. Rel. 86(1), 33–48 (2003).
- 11 Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. J. Control. Rel. 133(1), 11–17 (2009).
- 12 . PLGA/TPGS nanoparticles for controlled release of paclitaxel: effects of the emulsifier and drug loading ratio. Pharm. Res. 20(11), 1864–1872 (2003).
- 13 . method poly (ethylene glycol)-poly (lactide)(MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials 25(14), 2843–2849 (2004).
- 14 . Long-circulating poly (ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharm. Res. 19(7), 1061–1067 (2002).
- 15 Development of gelatin nanoparticles with biotinylated EGF conjugation for lung cancer targeting. Biomaterials 28(27), 3996–4005 (2007).
- 16 . Adenosine conjugated lipidic nanoparticles for enhanced tumor targeting. Int. J. Pharm. 486(1–2), 287–296 (2015).
- 17 . Lactoferrin bioconjugated solid lipid nanoparticles: a new drug-delivery system for potential brain targeting. J. Drug Target. 24(3), 212–223 (2016).
- 18 . Novel multifunctional biocompatible gelatin-oleic acid conjugate: self-assembled nanoparticles for drug delivery. J. Biomed. Nanotechnol. 9(8), 1416–1431 (2013). • The potential of hydrophobized gelatin conjugates to form self-assembled nanoparticles is highlighted.
- 19 . Biodistribution and pharmacokinetics in rats and antitumor effect in various types of tumor-bearing mice of novel self-assembled gelatin-oleic acid nanoparticles containing paclitaxel. J. Biomed. Nanotechnol. 10(1), 154–165 (2014).
- 20 . New method and characterization of self-assembled gelatin–oleic nanoparticles using a desolvation method via carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction. Eur. J. Pharm. Biopharm. 89, 365–373 (2015). • The various techniques employed for characterization of hydrophobized gelatin nanoparticles are highlighted.
- 21 . Improved stability and enhanced oral bioavailability of atorvastatin-loaded stearic acid-modified gelatin nanoparticles. Pharm. Res. 34(7), 1505–1516 (2017). • The potential of hydrophobized gelatin nanoparticles for improving stability and oral bioavailability is showcased.
- 22 . Emerging roles of anacardic acid and its derivatives: a pharmacological overview. Basic Clin. Pharmacol. Toxicol. 110(2), 122–132 (2012). •• The role and various pharmacological actions of anacardic acid (AA) are highlighted.
- 23 . Development and characterization of self-aggregated nanoparticles from anacardoylated chitosan as a carrier for insulin. Carbohydr. Polym. 80(1), 285–290 (2010).
- 24 Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-κB–regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-κBα kinase, leading to potentiation of apoptosis. Blood 111(10), 4880–4891 (2008).
- 25 Anacardic acid inhibits estrogen receptor α–DNA binding and reduces target gene transcription and breast cancer cell proliferation. Mol. Cancer Ther. 9(3), 594–605 (2010).
- 26 . Anti-metastatic action of anacardic acid targets VEGF-induced signalling pathways in epithelial to mesenchymal transition. Drug Discov. Ther. 9(1), 53–65 (2015). • The potential of AA for targeting VEGF receptors is highlighted.
- 27 Co-delivery of docetaxel and gemcitabine by anacardic acid modified self-assembled albumin nanoparticles for effective breast cancer management. Acta Biomater. 73, 424–436 (2018). •• The potential role of AA for targeting nuclear and perinuclear region of cancer cells is highlighted.
- 28 . Gelatin nanoparticles by two step desolvation a new preparation method, surface modifications and cell uptake. J. Microencapsul. 17(2), 187–193 (2000).
- 29 . Enhanced antitumor efficacy and reduced toxicity of docetaxel-loaded estradiol-functionalized stealth polymeric nanoparticles. Mol. Pharm. 12(11), 3871–3884 (2015).
- 30 Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway. Biomaterials 28(18), 2876–2884 (2007).
- 31 . Improved oral bioavailability, therapeutic efficacy, and reduced toxicity of tamoxifen-loaded liquid crystalline nanoparticles. AAPS PharmSciTech 19(1), 460–469 (2018).
- 32 . Polyelectrolyte stabilized multilayered liposomes for oral delivery of paclitaxel. Biomaterials 33(28), 6758–6768 (2012).
- 33 . Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy. Clin. Cancer Res. 10(22), 7677–7684 (2004).
- 34 Layer-by-layer-coated gelatin nanoparticles as a vehicle for delivery of natural polyphenols. ACS Nano 3(7), 1877–1885 (2009).
- 35 . Beyond the ligand-binding pocket: targeting alternate sites in nuclear receptors. Med. Res. Rev. 33(5), 1081–1118 (2013).
- 36 . Cell proliferation inhibitory and apoptosis-inducing properties of anacardic acid and lunasin in human breast cancer MDA-MB-231 cells. Food Chem. 125(2), 630–636 (2011).
- 37 . An inside view: VEGF receptor trafficking and signaling. Physiology 27(4), 213–222 (2012).