Skip to main content

Advertisement

SpringerLink
Log in

Preparation and Characterization of PLGA–PEG–PLGA Nanoparticles Containing Salidroside and Tamoxifen for Breast Cancer Therapy

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Nanoparticles (NPs) containing the hydrophilic drug salidroside (Sal) and the hydrophobic drug tamoxifen (Tam) were prepared using a triblock copolymer poly(lactic-co-glycolic acid) (PLGA)–poly(ethylene glycol) (PEG)–PLGA to achieve synergism in the treatment of breast cancer. The double emulsion (w/o/w) method was used to prepare Sal–Tam NPs with an average particle size of 275.3 ± 44.0 nm, a polydispersity index of 0.302 ± 0.102, and a zeta potential of − 6.98 ± 2.99. The entrapment efficiency of the hydrophilic and hydrophobic components was 32.63% ± 0.73% and 49.18% ± 3.04%, respectively. On differential scanning calorimetry, the NPs showed the amorphous nature of both Sal and Tam. The sustained release of Sal and Tam from the NPs was significantly prolonged under physiological conditions (pH 7.4). The CCK-8 assay using the 4T1 cell line revealed a 1.7-fold decrease in the IC50 value for Sal–Tam NPs when compared with free Tam. The in vivo anti-tumor effect was assessed in BALB/c mice, and the results demonstrated that these NPs decreased the tumor volume compared with saline and showed high anti-tumor activity. A pharmacokinetic study showed significant enhancement of the bioavailability of Tam in Sal–Tam NPs compared with free Tam in suspension. The intracellular and mitochondrial anti-oxidative effect of Sal was thought to be attributed to the promising anti-tumor effect of drug co-delivery. This study confirmed that the use of Sal–Tam NPs may be a promising approach in breast cancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Harbeck N, Gnant M. Breast cancer. Lancet. 2017;389:1134–50.

    Article  Google Scholar 

  2. Anampa J, Makower D, Sparano JA. Progress in adjuvant chemotherapy for breast cancer: an overview. BMC Med. 2015;13:195.

    Article  Google Scholar 

  3. Kumari P, Ghosh B, Biswas S. Nanocarriers for cancer-targeted drug delivery. J Drug Target. 2016;24:179–91.

    Article  CAS  Google Scholar 

  4. Nounou MI, ElAmrawy F, Ahmed N, Abdelraouf K, Goda S, Syed-Sha-Qhattal H. Breast cancer: conventional diagnosis and treatment modalities and recent patents and technologies. Breast Cancer (Auckl). 2015;9:17–34.

    CAS  Google Scholar 

  5. Xu X, Ho W, Zhang X, Bertrand N, Farokhzad O. Cancer nanomedicine: from targeted delivery to combination therapy. Trends Mol Med. 2015;21:223–32.

    Article  CAS  Google Scholar 

  6. Van Elk M, Murphy BP, Eufrásio-da-Silva T, O’Reilly DP, Vermonden T, Hennink WE, et al. Nanomedicines for advanced cancer treatments: transitioning towards responsive systems. Int J Pharm. 2016;515:132–64.

    Article  Google Scholar 

  7. Núñez C, Capelo JL, Igrejas G, Alfonso A, Botana LM, Lodeiro C. An overview of the effective combination therapies for the treatment of breast cancer. Biomaterials. 2016;97:34–50.

    Article  Google Scholar 

  8. Wang H, Yu J, Lu X, He X. Nanoparticle systems reduce systemic toxicity in cancer treatment. Nanomedicine (London). 2016;11:103–6.

    Article  CAS  Google Scholar 

  9. Kemp JA, Shim MS, Heo CY, Kwon YJ. “Combo” nanomedicine: co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy. Adv Drug Deliv Rev. 2016;98:3–18.

    Article  CAS  Google Scholar 

  10. Katiyar SS, Muntimadugu E, Rafeeqi TA, Domb AJ, Khan W. Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment. Drug Deliv. 2016;23:2608–16.

    CAS  PubMed  Google Scholar 

  11. Tang X, Liang Y, Feng X, Zhang R, Jin X, Sun L. Co-delivery of docetaxel and poloxamer 235 by PLGA-TPGS nanoparticles for breast cancer treatment. Mater Sci Eng C Mater Biol Appl. 2015;49:348–55.

    Article  CAS  Google Scholar 

  12. Vivek R, Thangam R, NipunBabu V, Rejeeth C, Sivasubramanian S, Gunasekaran P, et al. Multifunctional her2-antibody conjugated polymeric nanocarrier- based drug delivery system for multi-drug-resistant breast cancer therapy. ACS Appl Mater Interfaces. 2014;6:6469–80.

    Article  CAS  Google Scholar 

  13. Rossi L, Pagani O. Adjuvant endocrine therapy in breast cancer: evolving paradigms in premenopausal women. Curr Treat Options in Oncol. 2017;18:28.

    Article  Google Scholar 

  14. Maji R, Dey NS, Satapathy BS, Mukherjee B, Mondal S. Preparation and characterization of tamoxifen citrate loaded nanoparticles for breast cancer therapy. Int J Nanomedicine. 2014;2014(9):3107–18.

    Google Scholar 

  15. Thakur CK, Thotakura N, Kumar R, Kumar P, Singh B, Chitkara D, et al. Chitosan-modified PLGA polymeric nanocarriers with better delivery potential for tamoxifen. Int J Biol Macromol. 2016;93:381–9.

    Article  CAS  Google Scholar 

  16. Zhao X, Lu Y, Tao Y, Huang Y, Wang D, Hu Y, et al. Salidroside liposome formulation enhances the activity of dendritic cells and immune responses. Int Immunopharmacol. 2013;17:1134–40.

    Article  CAS  Google Scholar 

  17. Peng H, Dong R, Wang S, Zhang Z, Luo M, Bai C, et al. A pH-responsive nano-carrier with mesoporous silica nanoparticles cores and poly(acrylic acid) shell-layers: fabrication, characterization and properties for controlled release of salidroside. Int J Pharm. 2013;446:153–9.

    Article  CAS  Google Scholar 

  18. Yu G, Li N, Zhao Y, Wang W, Feng XL. Salidroside induces apoptosis in human ovarian cancer SKOV3 and A2780 cells through the p53 signaling pathway. Oncol Lett. 2018;15:6513–8.

    PubMed  PubMed Central  Google Scholar 

  19. Fan XJ, Wang Y, Wang L, Zhu M. Salidroside induces apoptosis and autophagy in human colorectal cancer cells through inhibition of pi3k/akt/mtor pathway. Oncol Rep. 2016;36:3559–67.

    Article  CAS  Google Scholar 

  20. Zeng W, Xiao T, Cai A, Cai W, Liu H, Liu J, et al. Inhibiting ROS-TFEB-dependent autophagy enhances salidroside-induced apoptosis in human chondrosarcoma cells. Cell Physiol Biochem. 2017;43:1487–502.

    Article  CAS  Google Scholar 

  21. Lv C, Huang Y, Liu ZX, Yu D, Bai ZM. Salidroside reduces renal cell carcinoma proliferation by inhibiting jak2/stat3 signaling. Cancer Biomark. 2016;17:41–7.

    Article  CAS  Google Scholar 

  22. Wang J, Li JZ, Lu AX, Zhang KF, Li BJ. Anticancer effect of salidroside on A549 lung cancer cells through inhibition of oxidative stress and phospho-p38 expression. Oncol Lett. 2016;7:1159–64.

    Article  Google Scholar 

  23. Biswas S, Kumari P, Lakhani PM, Ghosh B. Recent advances in polymeric micelles for anti-cancer drug delivery. Eur J Pharm Sci. 2016;83:184–202.

    Article  CAS  Google Scholar 

  24. Sadat Tabatabaei Mirakabad F, Nejati-Koshki K, Akbarzadeh A, Yamchi MR, Milani M, Zarghami N, et al. PLGA-based nanoparticles as cancer drug delivery systems. Asian Pac J Cancer Prev. 2014;15:517–35.

    Article  Google Scholar 

  25. Zhang K, Tang X, Zhang J, Lu W, Lin X, Zhang Y, et al. PEG-PLGA copolymers: their structure and structure-influenced drug delivery applications. J Control Release. 2014;10:77–86.

    Article  CAS  Google Scholar 

  26. Oerlemans C, Bult W, Bos M, Storm G, Nijsen JF, Hennink WE. Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res. 2010;27:2569–89.

    Article  CAS  Google Scholar 

  27. Yan Q, Xiao LQ, Tan L, Sun W, Wu T, Chen LW, et al. Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics. J Biomed Mater Res A. 2015;103:3580–9.

    Article  CAS  Google Scholar 

  28. Ci T, Chen L, Yu L, Ding J. Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel. Sci Rep. 2014;4:5473.

    Article  CAS  Google Scholar 

  29. Ma H, He C, Cheng Y, Yang Z, Zang J, Liu J, et al. Localized co-delivery of doxorubicin, cisplatin, and methotrexate by thermosensitive hydrogels for enhanced osteosarcoma treatment. ACS Appl Mater Interfaces. 2015;16:27040–8.

    Article  Google Scholar 

  30. Anari E, Akbarzadeh A, Zarghami N. Chrysin-loaded PLGA-PEG nanoparticles designed for enhanced effect on the breast cancer cell line. Artif Cells Nanomed Biotechnol. 2016;44:1410–6.

    CAS  PubMed  Google Scholar 

  31. Zhang J, Li Y, Gao W, Repka MA, Wang Y, Chen M. Andrographolide-loaded PLGA-PEG-PLGA micelles to improve its bioavailability and anticancer efficacy. Expert Opin Drug Deliv. 2014;11:1367–80.

    Article  CAS  Google Scholar 

  32. Tolosa L, Gómez-Lechón MJ, Donato MT. High-content screening technology for studying drug-induced hepatotoxicity in cell models. 2015;89:1007–22.

  33. Mattiazzi Usaj M, Styles EB, Verster AJ, Friesen H, Boone C, Andrews BJ. High-content screening for quantitative cell biology. Trends Cell Biol. 2016;26:598–611.

    Article  CAS  Google Scholar 

  34. Krisnamurti DG, Louisa M, Anggraeni E, Wanandi SI. Drug efflux transporters are overexpressed in short-term tamoxifen-induced MCF7 breast cancer cells. Adv Pharmacol Sci. 2016:6702424.

  35. Yuan Y, Cai T, Xia X, Zhang R, Chiba P, Cai Y. Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer. Drug Deliv. 2016;23:3350–7.

    Article  CAS  Google Scholar 

  36. Li S, Zhao Q, Wang B, Yuan S, Wang X, Li K. Quercetin reversed MDR in breast cancer cells through down-regulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation. Phytother Res. 2018;32(8):1530–6.

    Article  CAS  Google Scholar 

  37. Surya Sandeep M, Sridhar V, Puneeth Y, Ravindra Babu P, Naveen Babu K. Enhanced oral bioavailability of felodipine by naringenin in Wistar rats and inhibition of P-glycoprotein in everted rat gut sacs in vitro. Drug Dev Ind Pharm. 2014;40(10):1371–7.

    Article  CAS  Google Scholar 

  38. Jain AK, Thanki K, Jain S. Co-encapsulation of tamoxifen and quercetin in polymeric nanoparticles: implications on oral bioavailability, antitumor efficacy, and drug-induced toxicity. Mol Pharm. 2013;10(9):3459–574.

    Article  CAS  Google Scholar 

  39. Sandhu PS, Kumar R, Beg S, Jain S, Kushwah V, Katare OP, et al. Natural lipids enriched self-nano-emulsifying systems for effective co-delivery of tamoxifen and naringenin: systematic approach for improved breast cancer therapeutics. Nanomedicine. 2017;13(5):1703–13.

    Article  CAS  Google Scholar 

  40. Chiang HM, Chen HC, Wu CS, Wu PY, Wen KC. Rhodiola plants: chemistry and biological activity. J Food Drug Anal. 2015;23:359–69.

    Article  CAS  Google Scholar 

  41. Zhao G, Shi A, Fan Z, Du Y. Salidroside inhibits the growth of human breast cancer in vitro and in vivo. Oncol Rep. 2015;33:2553–60.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the grant from the National Natural Science Foundation of China (No. 81873191).

Author information

Author notes

  1. Xuan Yu and Lili Sun contributed equally to this work.

Authors and Affiliations

  1. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

    Xuan Yu, Lejun Tan, Meng Wang, Jiaxin Pi, Miaomiao Jiang & Nan Li

  2. School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China

    Lili Sun & Xiaoliang Ren

Authors
  1. Xuan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lili Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lejun Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaoliang Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiaxin Pi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Miaomiao Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Meng Wang or Xiaoliang Ren.

Ethics declarations

All animal experiments were conducted with approval from Tianjin International Joint Academy of Biomedicine (Tianjin, China).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, X., Sun, L., Tan, L. et al. Preparation and Characterization of PLGA–PEG–PLGA Nanoparticles Containing Salidroside and Tamoxifen for Breast Cancer Therapy. AAPS PharmSciTech 21, 85 (2020). https://doi.org/10.1208/s12249-019-1523-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-019-1523-8

KEY WORDS

Search

Navigation