STM Journals Peer-reviewed research from Consortium e-Learning Network

Journal of Polymer & Composites Original Research

Engineering of PEG-b-PCL/Pluronic F127 Polymeric Composite Micelles for Controlled Co-Delivery of Docetaxel and Curcumin in Prostate Cancer Therapy

  1. Mahesh M. Nosenoor Department of Pharmacy Practice, KLE College of Pharmacy, Bengaluru, KLE Academy of Higher Education and Research, Belagavi
  2. Sunil Kumar Singh Department of Pharmacology, United Institute of Pharmacy (Affiliated to Dr. APJ Abdul Kalam Technical University, Lucknow), A-31/1, UPSIDC Industrial Area, Naini, Prayagraj
  3. Anubi Badhani Department of Pharmacognosy, Shri Guru Ram Rai University, Dehradun
  4. Raj K. Keservani Laboratory of Pharmaceutics, Faculty of B. Pharmacy, CSM Group of Institutions, Prayagraj
  5. Sujit Appasaheb Jadhav Department of Pharmaceutics, KCT’S R G Sapkal College of Pharmacy, Anjaneri, Nashik
  6. Sachin Nathu Kapse Department of Pharmaceutical Chemistry, SES Matoshri College of Pharmacy, Mhasrul, Nashik
  7. Saurabh Das Vaishnaw Department of Pharmacognosy, Tagore Institute of Pharmacy and Research Sakri, Bilaspur (C.G.), Bilaspur

Abstract

Polymeric composite nanocarriers made from amphiphilic block copolymers are popular for their customisable architecture, self-assembly behaviour, and drug release control. A PEG-b-PCL/Pluronic F127 micellar composite was developed and tested as a multifunctional nanocarrier for docetaxel and curcumin administration.

The amphiphilic block copolymers Pluronic® F127 and PEG-b-PCL were employed to generate polymeric micelles using solvent evaporation-assisted self-assembly. The optimised polymer composite showed good colloidal stability and uniform size distribution with a zeta potential of -21.4 ± 2.1 mV, polydispersity index of 0.172 ± 0.014, and particle size of 118.6 ± 4.3 nm. Both DTX and CUR achieved encapsulation efficiencies of 91.8 ± 2.4% and 88.5 ± 1.9%, respectively.The polymeric core successfully contained both drugs, resulting in an amorphous distribution within the matrix, as confirmed by FTIR, DSC, and XRD examinations. The micellar composite showed sustained and pH-responsive drug release, with DTX release of 82.9 ± 2.8% and CUR of 82.7 ± 3.1% over 72 hours at pH 5.5. A 3.8-fold increase in intracellular drug accumulation was seen in PC-3 prostate cancer cells compared to free medicines. The co-loaded micelles showed greater cytotoxicity, as indicated by an IC50 value of 1.84 ± 0.12 µg/mL. Low systemic toxicity and 74.3% tumour inhibition were seen in in vivo tests on mice with tumours. Results indicate that the PEG-b-PCL/Pluronic F127 polymeric composite is promising as a prostate cancer nanocarrier.

Keywords

References (32)

  1. Alven S, Aderibigbe BA. Efficacy of polymer-based nanocarriers for co-delivery of curcumin and selected anticancer drugs. Nanomaterials (Basel). 2020;10(8):1556. doi:10.3390/nano10081556.
  2. Yan J, Wang Y, Zhang X, Liu S, Tian C, Wang H. Targeted nanomedicine for prostate cancer therapy: docetaxel and curcumin co-encapsulated lipid-polymer hybrid nanoparticles for enhanced anti-tumor activity in vitro and in vivo. Drug Deliv. 2016;23(5):1757-1762. https://doi.org/10.3109/10717544.2015.1069423
  3. Eftekhari RB, Maghsoudnia N, Samimi S, Zamzami A, Dorkoosh FA. Co-delivery nanosystems for cancer treatment: a review. Pharm Nanotechnol. 2019;7(2):90-112. doi:10.2174/2211738507666190321112237.
  4. Afsharzadeh M, Hashemi M, Mokhtarzadeh A, Abnous K, Ramezani M. Recent advances in co-delivery systems based on polymeric nanoparticles for cancer treatment. Artif Cells Nanomed Biotechnol. 2018;46(6):1095-1110. https://doi.org/10.1080/21691401.2017.1376675
  5. Dian C, Qian Z, Ran M, Yan X, Dian L. Co-delivery of docetaxel and curcumin functionalized mixed micelles for the treatment of drug-resistant breast cancer by oral administration. Int J Nanomedicine. 2024;19:8603-8620. doi:10.2147/IJN.S472445.
  6. Yan J, Wang Y, Jia Y, Liu S, Tian C, Pan W, et al. Co-delivery of docetaxel and curcumin prodrug via dual-targeted nanoparticles with synergistic antitumor activity against prostate cancer. Biomed Pharmacother. 2017;88:374-383. doi:10.1016/j.biopha.2016.12.138.
  7. Chen Y, Deng Y, Zhu C, Xiang C. Anti-prostate cancer therapy: aptamer-functionalized, curcumin and cabazitaxel co-delivered, tumor-targeted lipid-polymer hybrid nanoparticles. Biomed Pharmacother. 2020;127:110181. doi:10.1016/j.biopha.2020.110181.
  8. Ding Y, Ding Y, Wang Y, Wang C, Gao M, Xu Y, et al. Soluplus®/TPGS mixed micelles for co-delivery of docetaxel and piperine for combination cancer therapy. Pharm Dev Technol. 2020;25(1):107-115. doi:10.1080/10837450.2019.1679834.
  9. Ma W, Guo Q, Li Y, Wang X, Wang J, Tu P. Co-assembly of doxorubicin and curcumin targeted micelles for synergistic delivery and improving anti-tumor efficacy. Eur J Pharm Biopharm. 2017;112:209-223. doi:10.1016/j.ejpb.2016.11.033.
  10. Xiong K, Zhang Y, Wen Q, Luo J, Lu Y, Wu Z, et al. Co-delivery of paclitaxel and curcumin by biodegradable polymeric nanoparticles for breast cancer chemotherapy. Int J Pharm. 2020;589:119875. doi:10.1016/j.ijpharm.2020.119875.
  11. Ye X, Chen X, He R, Meng W, Chen W, Wang F, et al. Enhanced anti-breast cancer efficacy of co-delivery liposomes of docetaxel and curcumin. Front Pharmacol. 2022;13:969611. doi:10.3389/fphar.2022.969611.
  12. Deng L, Zhu X, Yu Z, Li Y, Qin L, Liu Z, et al. Novel T7-modified pH-responsive targeted nanosystem for co-delivery of docetaxel and curcumin in the treatment of esophageal cancer. Int J Nanomedicine. 2020;15:7745-7762. doi:10.2147/IJN.S257312.
  13. Hu Y, Ran M, Wang B, Lin Y, Cheng Y, Zheng S. Co-delivery of docetaxel and curcumin via nanomicelles for enhancing anti-ovarian cancer treatment. Int J Nanomedicine. 2020;15:9703-9715. doi:10.2147/IJN.S274083.
  14. Guo X, Zhao Z, Chen D, Qiao M, Wan F, Cun D, et al. Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors. Asian J Pharm Sci. 2019;14(1):78-85. doi:10.1016/j.ajps.2018.03.002.
  15. Wang J, Ma W, Tu P. Synergistically improved anti-tumor efficacy by co-delivery doxorubicin and curcumin polymeric micelles. Macromol Biosci. 2015;15(9):1252-1261. doi:10.1002/mabi.201500043.
  16. Li K, Zhan W, Chen Y, Jha RK, Chen X. Docetaxel and doxorubicin codelivery by nanocarriers for synergistic treatment of prostate cancer. Front Pharmacol. 2019;10:1436. doi:10.3389/fphar.2019.01436.
  17. Farhoudi L, Hosseinikhah SM, Kazemi-Beydokhti A, Arabi L, Alavizadeh SH, Moosavian SA, et al. pH-sensitive polymeric micelles enhance the co-delivery of doxorubicin and docetaxel: an emerging modality for treating breast cancer. Cancer Nanotechnol. 2024;15:37. doi:10.1186/s12645-024-00275-1.
  18. Bhosale RR, Gangadharappa HV, Hani U, Osmani RAM, Vaghela R, Kulkarni PK, et al. Current perspectives on novel drug delivery systems and therapies for management of prostate cancer: an inclusive review. Curr Drug Targets. 2017;18(11):1233-1249. doi:10.2174/1389450117666160613103705.
  19. Jamali B, Jamali S, Vaghefi Moghaddam S, Firoozrai M, Davaran S, Abedi F. Targeted co-delivery of paclitaxel and chrysin by hyaluronate/chitosan-coated polymeric nanoparticles for prostate cancer chemotherapy. Int J Polym Mater Polym Biomater. 2024;73(14):1238-1251. doi:10.1080/00914037.2023.2277219.
  20. Zhang L, Lin Z, Chen Y, Gao D, Wang P, Lin Y, et al. Co-delivery of docetaxel and resveratrol by liposomes synergistically boosts antitumor efficiency against prostate cancer. Eur J Pharm Sci. 2022;174:106199. doi:10.1016/j.ejps.2022.106199.
  21. Khodaverdi E, Tayarani-Najaran Z, Minbashi E, Alibolandi M, Hosseini J, Sepahi S, et al. Docetaxel-loaded mixed micelles and polymersomes composed of poly(caprolactone)-poly(ethylene glycol) (PEG-PCL) and poly(lactic acid)-poly(ethylene glycol) (PEG-PLA): preparation and in-vitro characterization. Iran J Pharm Res. 2019;18(1):142-155. PMID: 31089351
  22. Pan J, Rostamizadeh K, Filipczak N, Torchilin VP. Polymeric co-delivery systems in cancer treatment: an overview on component drugs' dosage ratio effect. Molecules. 2019;24(6):1035. doi:10.3390/molecules24061035.
  23. Zhang R, Zhai BT, Qiao JX, Zhang D, Wang AJ, Yang XY, et al. Research progress of docetaxel nano-drug delivery system in the treatment of breast cancer. Int J Nanomedicine. 2025;20:14571-14611. doi:10.2147/IJN.S540777.
  24. Yousefnezhad M, Babazadeh M, Davaran S, Akbarzadeh A, Pazoki-Toroudi H. Preparation and in-vitro evaluation of PCL-PEG-PCL nanoparticles for doxorubicin-ezetimibe co-delivery against PC3 prostate cancer cell line. Chem Rev Lett. 2024;7(2):159-172. https://doi.org/10.22034/crl.2024.436907.1285
  25. Nwabuife JC, Sekhoacha MP. Liposomal delivery systems for improved delivery of docetaxel against prostate cancer. Int J Nanomedicine. 2026;21:553994. doi:10.2147/IJN.S553994.
  26. Zhu X, Yu Z, Feng L, Deng L, Fang Z, Liu Z, et al. Chitosan-based nanoparticle co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer. Carbohydr Polym. 2021;268:118237. doi:10.1016/j.carbpol.2021.118237.
  27. Jurczyk M, Kasperczyk J, Wrześniok D, Beberok A, Jelonek K. Nanoparticles loaded with docetaxel and resveratrol as an advanced tool for cancer therapy. Biomedicines. 2022;10(5):1187. doi:10.3390/biomedicines10051187.
  28. Hari SK, Gauba A, Shrivastava N, Tripathi RM, Jain SK, Pandey AK. Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system. Drug Deliv Transl Res. 2023;13(1):135-163. doi:10.1007/s13346-022-01197-4.
  29. Torchelsen FKVS, Lages EB, de Oliveira MA, Barros ALB, Mosqueira VCF. Drug combination in polymeric nanocarriers for chemotherapy of cancer: preclinical outcomes in the last ten years. Pharmaceuticals (Basel). 2026;19(2):248. doi:10.3390/ph19020248.
  30. Almutairy B, Alharthi S, Ebrahimi Shahmabadi H, Alavi SE. Use of nanoemulsion for co-delivery of silibinin and cabazitaxel for prostate cancer treatment. Drug Dev Ind Pharm. 2025;51(11):1591-1606. doi:10.1080/03639045.2025.2552392.
  31. Li Y, Zhang H, Zhai GX. Intelligent polymeric micelles: development and application as drug delivery for docetaxel. J Drug Target. 2017;25(4):285-295. doi:10.1080/1061186X.2016.1245309.
  32. Kim CH, Kim BD, Lee TH, Kim HK, Lyu MJ, Yoon YI, et al. Synergistic co-administration of docetaxel and curcumin to chemoresistant cancer cells using PEGylated and RIPL peptide-conjugated nanostructured lipid carriers. Cancer Nanotechnol. 2022;13:17. doi:10.1186/s12645-022-00119-w.
Support