Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
REVIEWS   (Open Access)

Advancements in Nanotechnology-Based Paclitaxel Delivery Systems: Systematic Review on Overcoming Solubility, Toxicity, and Drug Resistance Challenges in Cancer Therapy

Balisa Mosisa Ejeta1*, Malay K Das1, Sanjoy Das1

+ Author Affiliations

Journal of Angiotherapy 8(10) 1-7 https://doi.org/10.25163/angiotherapy.88109973

Submitted: 13 August 2024  Revised: 16 October 2024  Published: 18 October 2024 

Abstract

Background: Paclitaxel (PTX) is a potent chemotherapeutic widely used to treat cancers, including breast and ovarian cancer. However, its poor water solubility, severe side effects, and susceptibility to multidrug resistance (MDR) limit its clinical effectiveness. Recent research focuses on nanotechnology-based delivery systems, such as nanoparticles, liposomes, and dendrimers, to enhance PTX solubility, bioavailability, and targeted delivery. This systematic review analyzed studies from 2019 to 2023 that explore advancements in PTX delivery, focusing on improving therapeutic outcomes and reducing toxicity. Methods: A systematic search was conducted using PubMed, Scopus, Google Scholar, and Web of Science. Forty-five primary research studies meeting inclusion criteria for nanotechnology-based systems, targeted delivery, and MDR strategies were analyzed for improvements in PTX delivery efficacy. Results: The review identified significant advancements in PTX delivery through nanoparticle and targeted systems. Polymer-based nanoparticles, ligand-conjugated carriers,

and co-delivery systems with MDR inhibitors showed improved PTX solubility, stability, and selective targeting. Theragnostic platforms combining diagnostics and therapy offered real-time tracking, enhancing personalized treatment. Conclusion: While nanotechnology-based PTX delivery shows promise in overcoming PTX's limitations, challenges remain, particularly in nanoparticle stability, tumor microenvironment barriers, and regulatory hurdles. Future research should address these challenges to enable the clinical translation of PTX systems, providing more effective, accessible cancer treatments worldwide.

Keywords: Paclitaxel delivery systems, Nanotechnology-based chemotherapy, Targeted drug delivery, Multidrug resistance (MDR), Cancer Nanomedicine

References

Alexis, F., Pridgen, E. M., Langer, R., & Farokhzad, O. C. (2010). Nanoparticle technologies for cancer therapy. In Handbook of Experimental Pharmacology (pp. 55–86). https://doi.org/10.1007/978-3-642-00477-3_2

Berg, S. L., Tolcher, A., O’Shaughnessy, J. A., Denicoff, A. M., Noone, M., et al. (1995). Effect of R-verapamil on the pharmacokinetics of paclitaxel in women with breast cancer. Journal of Clinical Oncology, 13, 2039–2042. https://doi.org/10.1200/JCO.1995.13.8.2039

Bhardwaj, V., Ankola, D. D., Gupta, S., Schneider, M., Lehr, C. M., et al. (2009). PLGA nanoparticles stabilized with cationic surfactant: Safety studies and application in oral delivery of paclitaxel to treat chemical-induced breast cancer in rat. Pharmaceutical Research, 26, 2495–2503. https://doi.org/10.1007/s11095-009-9965-4

Chakravarthi, S. S., & Robinson, D. H. (2011). Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles. International Journal of Pharmaceutics, 409, 111–120. https://doi.org/10.1016/j.ijpharm.2011.02.034

Chen, G., Roy, I., Yang, C., & Prasad, P. (2020). Nanochemistry and nanomedicine for nanoparticle-based targeted drug delivery. Chemical Reviews, 120(5), 8814-8872. https://doi.org/10.1021/acs.chemrev.9b00881

Danhier, F., Lecouturier, N., Vroman, B., Jérôme, C., Marchand-Brynaert, J., et al. (2009). Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation. Journal of Controlled Release, 133, 11–17. https://doi.org/10.1016/j.jconrel.2008.09.086

Dong, Y., & Feng, S. S. (2007). Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles prepared by high pressure homogenization for paclitaxel chemotherapy. International Journal of Pharmaceutics, 342, 208–214. https://doi.org/10.1016/j.ijpharm.2007.04.031

Fonseca, C., Simões, S., & Gaspar, R. (2002). Paclitaxel-loaded PLGA nanoparticles: Preparation, physicochemical characterization and in vitro anti-tumoral activity. Journal of Controlled Release, 83, 273–286. https://doi.org/10.1016/s0168-3659(02)00212-2

Fracasso, P. M., Westervelt, P., Fears, C. L., Rosen, D. M., Zuhowski, E. G., et al. (2000). Phase I study of paclitaxel in combination with a multidrug resistance modulator, PSC 833 (Valspodar), in refractory malignancies. Journal of Clinical Oncology, 18, 1124–1134. https://doi.org/10.1200/JCO.2000.18.5.1124

Gallo, J. M., Li, S., Guo, P., Reed, K., & Ma, J. (2003). The effect of P-glycoprotein on paclitaxel brain and brain tumor distribution in mice. Cancer Research, 63, 5114–5117.

Gelderblom, H., Verweij, J., Nooter, K., & Sparreboom, A. (2001). Cremophor EL: The drawbacks and advantages of vehicle selection for drug formulation. European Journal of Cancer, 37, 1590–1598. https://doi.org/10.1016/s0959-8049(01)00171-x

Haley, B., & Frenkel, E. (2008). Nanoparticles for drug delivery in cancer treatment. Urology Oncology, 26, 57–64. https://doi.org/10.1016/j.urolonc.2007.03.015

Jain, R. K., & Stylianopoulos, T. (2010). Delivering nanomedicine to solid tumors. Nature Reviews Clinical Oncology, 7, 653–664. https://doi.org/10.1038/nrclinonc.2010.139

Jiang, X., Liu, L., & Guo, X. (2020). Overcoming the tumor microenvironment: Paclitaxel nanoparticles with penetration capabilities. Advanced Drug Delivery Reviews, 159, 28-41. https://doi.org/10.1016/j.addr.2020.03.007

Jin, C., Bai, L., Wu, H., Liu, J., Guo, G., et al. (2008). Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro. Cancer Biology & Therapy, 7, 911–916. https://doi.org/10.4161/cbt.7.6.5912

Jin, C., Bai, L., Wu, H., Song, W., Guo, G., et al. (2009). Cytotoxicity of paclitaxel incorporated in PLGA nanoparticles on hypoxic human tumor cells. Pharmaceutical Research, 26, 1776–1784. https://doi.org/10.1007/s11095-009-9889-z

Jin, C., Wu, H., Liu, J., Bai, L., & Guo, G. (2007). The effect of paclitaxel-loaded nanoparticles with radiation on hypoxic MCF-7 cells. Journal of Clinical Pharmacy and Therapeutics, 32, 41–47. https://doi.org/10.1111/j.1365-2710.2007.00796.x

Jordan, M. A., & Wilson, L. (2004). Microtubules as a target for anticancer drugs. Nature Reviews Cancer, 4, 253–265. https://doi.org/10.1038/nrc1317

Kim, B. S., Kim, C. S., & Lee, K. M. (2008). The intracellular uptake ability of chitosan-coated poly(D,L-lactide-co-glycolide) nanoparticles. Archives of Pharmacal Research, 31, 1050–1054. https://doi.org/10.1007/s12272-001-1267-5

Kumar, A., Jena, S., & Khan, F. (2022). Biocompatible and biodegradable nanoparticles for paclitaxel delivery: Advances and challenges. Journal of Pharmaceutical Sciences, 111(3), 892-907. https://doi.org/10.1016/j.xphs.2021.12.025

Li, H., Zhang, M., & Wang, Y. (2019). Nanoparticle delivery systems for paclitaxel: A comprehensive review. Journal of Controlled Release, 310, 73-89. https://doi.org/10.1016/j.jconrel.2019.08.009

Shen, Z., Chen, T., & Shi, Y. (2021). Overcoming multidrug resistance in cancer therapy: Current strategies and emerging trends. Cancer Letters, 512, 20-34. https://doi.org/10.1016/j.canlet.2021.07.010

Sparreboom, A., van Tellingen, O., Nooijen, W. J., & Beijnen, J. H. (1996). Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Cancer Research, 56, 2112–2115.

Storm, G., Belliot, S. O., Daemen, T., & Lasic, D. D. (1995). Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system. Advanced Drug Delivery Reviews, 17, 31–48.

Sun, T., Zhang, L., & Wang, C. (2020). Theranostic applications of nanoparticles in cancer treatment. Molecular Pharmaceutics, 17(6), 1878-1894. https://doi.org/10.1021/acs.molpharmaceut.0c00075

Suri, S. S., Fenniri, H., & Singh, B. (2007). Nanotechnology-based drug delivery systems. Journal of Occupational Medicine and Toxicology, 2, 16. https://doi.org/10.1186/1745-6673-2-16

Wang, J., Sui, M., & Fan, W. (2010). Nanoparticles for tumor targeted therapies and their pharmacokinetics. Current Drug Metabolism, 11, 129–141. https://doi.org/10.2174/138920010791110827

Wang, Z., Zhang, Q., & He, X. (2021). Nanoparticle stability and drug release mechanisms in paclitaxel delivery. Drug Delivery and Translational Research, 11(2), 298-307. https://doi.org/10.1007/s13346-020-00799-3

Zhang, Z., Liu, H., & Li, J. (2020). Targeted delivery of paclitaxel using ligand-conjugated nanoparticles: An update. Journal of Nanobiotechnology, 18, 123. https://doi.org/10.1186/s12951-020-00762-4

Zhou, X., Wang, Y., & Li, W. (2021). Drug resistance in cancer: Current approaches and challenges in paclitaxel delivery. Advanced Drug Delivery Reviews, 170, 174-195. https://doi.org/10.1016/j.addr.2021.05.007

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