International Journal of Drug Delivery Technology
Volume 15, Issue 1

Design and Development of Solid Lipid Nanoparticles Drug Delivery Systems for Prolonged and Targeted Delivery of Fulvestrant

Dinesh Shinde, Ganesh Basarkar, Chandrashekhar Upasani 

SNJBs Sureshdada Jain College of Pharmacy, Chandwad, Nashik, Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India.

Received: 19th Dec, 2024; Revised: 5th Feb Jan, 2025; Accepted: 25th Feb, 2025; Available Online: 25th Mar, 2025

ABSTRACT

The research aims to design, formulate, and assess desired SLNs for poorly soluble anticancer drug Fulvestrant. The SLNs were made up of solid dispersion by high shear mixing and high pressure homogenization to make a very fine suspension. Drug loading, entrapment efficacy, particle size, and stability are the general parameters that were considered in this case for the different formulations; hence, optimization was performed through them. A good place to prove this preparation is an investigation of the saturation solubility of the Fulvestrant in various solvents, and subsequently determining which of them is clearly shown in 0.1 N HCl. Various observations of thermal analysis, that is DSC and XRD, indicated that the nanoparticles had stable, crystalline-like structure and, at the same time, favorable thermal properties. The optimized Batch B formulation was the one showing the highest drug loading and very high entrapment efficiency of about 70.8 and 95.2%, respectively. The particles normally had 150-nm size, while zeta potential was measured to be -220 mV. Ex-vivo diffusion studies successfully verified the drug release profiles of the nanoparticles, and the findings implied that Batch B exhibited 99.1% cumulative drug release for a 12-hour period. The pharmacokinetic studies indicated that the drug was released at a controlled rate and it had caused an increase in Tmax, which implied that there was an extended action of the drug. Stability studies verify Batch B as stable in both accelerated and long-term conditions. These studies flag the much value-adding potential of these SLNs as a good vehicle capable of delivering the improved pharmaceutical characteristics noted earlier for Fulvestrant.

Keywords: Solid Lipid Nanoparticles, Fulvestrant, Drug Delivery, Microemulsion Technique, Sustained Release, Cancer Treatment, Pharmacokinetics, Stability Studies

How to cite this article: Dinesh Shinde, Ganesh Basarkar, Chandrashekhar Upasani. Design, Development and Evaluation of Liposomal Formulations of Fulvestrant for Targeted Drug Delivery Breast Cancer. International Journal of Drug Delivery Technology, 2025;15(1):196-204. doi: 10.25258/ijddt.15.1.28

REFERENCES

  1. McShane N, Zaborowski A, O'Reilly M, McCartan D, Prichard R. Hormone Receptor Positive Breast Cancer in Young Women: A Review. Journal of Surgical Oncology. 2024.https://doi.org/10.1002/jso.27963
  2. Rej RK, Roy J, Allu SR. Therapies for the treatment of advanced/metastatic estrogen receptor-positive breast cancer: current situation and future directions. Cancers. 2024 Jan 27;16(3):552.https://doi.org/10.3390/cancers16030552
  3. Liu J, Rajasekaran N, Hossain A, Zhang C, Guo S, Kang B, Jung H, Kim H, Wang G. Fulvestrant-3-boronic acid (ZB716) demonstrates oral bioavailability and favorable pharmacokinetic profile in preclinical ADME studies. Pharmaceuticals. 2021 Jul 26;14(8):719.https://doi.org/10.3390/ph14080719
  4. Sahu T, Ratre YK, Chauhan S, Bhaskar LV, Nair MP, Verma HK. Nanotechnology based drug delivery system: Current strategies and emerging therapeutic potential for medical science. Journal of Drug Delivery Science and Technology. 2021 Jun 1;63:102487.https://doi.org/10.1016/j.jddst.2021.102487
  5. Viegas C, Patrício AB, Prata JM, Nadhman A, Chintamaneni PK, Fonte P. Solid lipid nanoparticles vs. nanostructured lipid carriers: a comparative review. Pharmaceutics. 2023 May 25;15(6):1593.https://doi.org/10.3390/pharmaceutics15061593
  6. Mohammed HA, Khan RA, Singh V, Yusuf M, Akhtar N, Sulaiman GM, Albukhaty S, Abdellatif AA, Khan M, Mohammed SA, Al-SubaiyelAM. Solid lipid nanoparticles for targeted natural and synthetic drugs delivery in high-incidence cancers, and other diseases: Roles of preparation methods, lipid composition, transitional stability, and release profiles in nanocarriers’ development. Nanotechnology Reviews. 2023 Feb 18;12(1):20220517.https://doi.org/10.1515/ntrev-2022-0517
  7. Wang W, Zhou M, Xu Y, Peng W, Zhang S, Li R, Zhang H, Zhang H, Cheng S, Wang Y, Wei X. Resveratrol-loaded TPGS-resveratrol-solid lipid nanoparticles for multidrug-resistant therapy of breast cancer: in vivo and in vitro study. Frontiers in Bioengineering and Biotechnology. 2021 Dec 7;9:762489.https://doi.org/10.3389/fbioe.2021.762489
  8. Malik Z, Parveen R, Abass S, Irfan Dar M, Husain SA, Ahmad S. Receptor-mediated targeting in breast cancer through solid lipid nanoparticles and its mechanism. Current Drug Metabolism. 2022 Aug 1;23(10):800-17.https://doi.org/10.2174/1389200223666220416213639
  9. Pandey S, Shaikh F, Gupta A, Tripathi P, Yadav JS. A recent update: solid lipid nanoparticles for effective drug delivery. Advanced Pharmaceutical Bulletin. 2021 May 16;12(1):17.https://doi.org/10.34172/apb.2022.007
  10. Nekkalapudi AR, Veldi VG, Pippalla S. A novel RP-HPLC method for estimating fulvestrant, benzoyl alcohol, and benzyl benzoate in injection formulation. American Journal of Analytical Chemistry. 2022 Jul 7;13(7):229-40.https://doi.org/10.4236/ajac.2022.137016
  11. Al-Owaidi MF, Mahdi MF. Synthesis and anti-breast cancer activity evaluation of the designed chlorobenzothiophene derivatives: Promising estrogen receptor alpha inhibitors. Egyptian Journal of Chemistry. 2023 Oct 1;66(10):431-41.https://doi.org/10.21608/ejchem.2023.153114.6633
  12. Ghosh S, Mandal S, Roy T, Ravikumar BV. A Novel RP–HPLC analytical method development and validation of fulvestrant injection as per ICH guidelines. Egyptian Journal of Chemistry. 2021 Apr 1;64(4):2047-55.https://dx.doi.org/10.21608/ejchem.2021.56503.3215
  13. Nsairat H, Al-Sulaibi M, Alshaer W. PEGylated nanoassemblies composed of edelfosine and fulvestrant drugs: In vitro antiproliferative effect against breast cancer cells. Journal of Drug Delivery Science and Technology. 2023 Aug 1;85:104612.https://doi.org/10.1016/j.jddst.2023.104612
  14. Maddiboyina B, Jhawat V, Nakkala RK, Desu PK, Gandhi S. Design expert assisted formulation, characterization and optimization of microemulsion based solid lipid nanoparticles of repaglinide. Progress in Biomaterials. 2021 Dec;10(4):309-20. https://doi.org/10.1007/s40204-021-00174-3
  15. Wang W, Huang Z, Li Y, Wang W, Shi J, Fu F, Huang Y, Pan X, Wu C. Impact of particle size and pH on protein corona formation of solid lipid nanoparticles: A proof-of-concept study. ActaPharmaceuticaSinica B. 2021 Apr 1;11(4):1030-46.https://doi.org/10.1016/j.apsb.2020.10.023
  16. Rampaka R, Ommi K, Chella N. Role of solid lipid nanoparticles as drug delivery vehicles on the pharmacokinetic variability of ErlotinibHCl. Journal of Drug Delivery Science and Technology. 2021 Dec 1;66:102886.https://doi.org/10.1016/j.jddst.2021.102886
  17. Ye J, Wang Q, Zhou X, Zhang N. Injectable actarit-loaded solid lipid nanoparticles as passive targeting therapeutic agents for rheumatoid arthritis. International journal of pharmaceutics. 2008 Mar 20;352(1-2):273-9.https://doi.org/10.1016/j.ijpharm.2007.10.014
  18. Imran B, ud Din F, Ali Z, Fatima A, Khan MW, Kim DW, Malik M, Sohail S, Batool S, Jawad M, Shabbir K. Statistically designed dexibuprofen loaded solid lipid nanoparticles for enhanced oral bioavailability. Journal of Drug Delivery Science and Technology. 2022 Nov 1;77:103904.https://doi.org/10.1016/j.jddst.2022.103904
  19. Bakshi V, Amarachinta PR, Chettupalli AK. Design, development and optimization of solid lipid nanoparticles of Rizatriptan for intranasal delivery: invitro&invivo assessment. Materials Today: Proceedings. 2022 Jan 1;66:2342-57.https://doi.org/10.1016/j.matpr.2022.06.329
  20. Garg A, Bhalala K, Tomar DS. In-situ single pass intestinal permeability and pharmacokinetic study of developed Lumefantrine loaded solid lipid nanoparticles. International journal of pharmaceutics. 2017 Jan 10;516(1-2):120-30.https://doi.org/10.1016/j.ijpharm.2016.10.064
  21. Mane VB, Killedar SG, More HN, Tare HL, Evaluation of acute oral toxicity of the Emblica officinalisPhytosome Formulation in Wistar Rats. International Journal of Drug Delivery Technology. 2022;12(4):1566-1570.https://doi.org/10.25258/ijddt.12.4.14
  22. Porbaha P, Ansari R, Kiafar MR, Bashiry R, Khazaei MM, Dadbakhsh A, Azadi A. A Comparative Mathematical Analysis of Drug Release from Lipid-Based Nanoparticles. AAPS PharmSciTech. 2024 Sep 5;25(7):208.https://doi.org/10.1208/s12249-024-02922-7
  23. Silva AC, Kumar A, Wild W, Ferreira D, Santos D, Forbes B. Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles. International journal of pharmaceutics. 2012 Oct 15;436(1-2):798-805.https://doi.org/10.1016/j.ijpharm.2012.07.058
  24. Gao Y, Gu W, Chen L, Xu Z, Li Y. The role of daidzein-loaded sterically stabilized solid lipid nanoparticles in therapy for cardio-cerebrovascular diseases. Biomaterials. 2008 Oct 1;29(30):4129-36.https://doi.org/10.1016/j.biomaterials.2008.07.008
  25. Ahmad S, Patil K, Koli G, Rahman BA, Barde L, Deshpande M, Tare H. Design, Development andCharacterization of Econazole loaded Nanoparticles for Topical Application. International Journal of Pharmaceutical QualityAssurance. 2023;14(2):358-362.https://doi.org/10.25258/ijpqa.14.2.20