Design and Development of Enzalutamide-Encapsulated PCL Nanoparticles for Prostate Cancer: A Box–Behnken Statistical Approach

Introduction, Materials & Methods, Characterization of Enzalutamide-loaded Polycaprolactone nanoparticles, Result and Discussion, Conclusion

Authors

  • Niranjan Panda Professor, School of Pharmacy, The Neotia University, Kolkota https://orcid.org/0000-0002-1821-7326
  • Sameena Begum Research scholar, Department of Pharmacy, Chaitanya Deemed to be University, Warangal-506001 https://orcid.org/0009-0001-5148-1241
  • Ch. Praveena Department of Pharmacy, Chaitanya Deemed to be University, Warangal, 506001, Telangana

Keywords:

Enzalutamide, PCL, IC₅₀, Prostate cancer, TEM

Abstract

This study presents the design and development of Enzalutamide-encapsulated polycaprolactone (PCL) nanoparticles for targeted prostate cancer therapy, employing a Box–Behnken statistical design to optimise formulation parameters. Nanoparticles were prepared via the emulsion solvent evaporation method and evaluated for particle size, entrapment efficiency (EE%), and zeta potential. The formulations exhibited particle sizes ranging from 148 nm to 219 nm, EE% between 70% and 92%, and zeta potentials from –13.4 mV to –32.5 mV, indicating good colloidal stability. Transmission electron microscopy (TEM) confirmed spherical morphology, while Fourier-transform infrared spectroscopy (FTIR) revealed no significant chemical interactions between Enzalutamide and PCL, confirming compatibility. Cytotoxicity studies demonstrated enhanced anticancer activity of the optimised nanoparticles, with a lower IC₅₀ (14.27µg/ml) value compared to pure Enzalutamide (22.24 µg/ml), suggesting improved cellular uptake and therapeutic efficacy. In the pharmacokinetic evaluation, Enzalutamide-loaded optimised nanoparticles exhibited a threefold enhancement in AUC (34.42 µg·h/mL) relative to the pure Enzalutamide suspension formulation (11.30 µg·h/mL), reflecting improved systemic bioavailability. These findings support the potential of PCL-based nanocarriers as an effective delivery system for Enzalutamide in prostate cancer treatment.

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Author Biographies

Niranjan Panda, Professor, School of Pharmacy, The Neotia University, Kolkota

Pharmaceutics

Sameena Begum, Research scholar, Department of Pharmacy, Chaitanya Deemed to be University, Warangal-506001

Research scholar, Department of Pharmacy, Chaitanya Deemed to be University, Warangal-506001

Ch. Praveena, Department of Pharmacy, Chaitanya Deemed to be University, Warangal, 506001, Telangana

Department of Pharmacy, Chaitanya Deemed to be University, Warangal, 506001, Telangana

References

1. Elmehrath AO, Afifi AM, Al-Husseini MJ, Saad AM, Wilson N, Shohdy KS, Pilie P, Sonbol MB, Alhalabi O. Causes of death among patients with metastatic prostate cancer in the US from 2000 to 2016. JAMA Network Open. 2021 Aug 2;4(8):e2119568.

2. Garner WB, Smith BD, Ludmir EB, Wakefield DV, Shabason J, Williams GR, Martin MY, Wang Y, Ballo MT, VanderWalde NA. Predicting future cancer incidence by age, race, ethnicity, and sex. Journal of Geriatric Oncology. 2023 Jan 1;14(1):101393.

3. Shafiekhani M, Shahabinezhad F, Tavakoli Z, Tarakmeh T, Haem E, Sari N, Nasirabadi S, Dehghani M. Quality of life associated with immunosuppressant treatment adherence in liver transplant recipients: A cross-sectional study. Frontiers in Pharmacology. 2023 Feb 24;14:1051350.

4. Armstrong AJ, Azad AA, Iguchi T, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Alcaraz A, Alekseev B, Shore ND, Gomez-Veiga F. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. Journal of Clinical Oncology. 2022 May 20;40(15):1616-22.

5. Podgoršek E, Mehra N, van Oort IM, Somford DM, Boerrigter E, van Erp NP. Clinical pharmacokinetics and pharmacodynamics of the next-generation androgen receptor inhibitor—darolutamide. Clinical Pharmacokinetics. 2023 Aug;62(8):1049-61.

6. AlMousa LA, Pandey P, Lakhanpal S, Kyada AK, Nayak PP, Hussain A, Hasan TN, Alagal RI, Khan F. An updated review deciphering the anticancer potential of pentacyclic triterpene lupeol and its nanoformulations. Frontiers in Pharmacology. 2025 May 9;16:1594901.

7. Das KP. Nanoparticles and convergence of artificial intelligence for targeted drug delivery for cancer therapy: Current progress and challenges. Frontiers in Medical Technology. 2023 Jan 6;4:1067144.

8. Pawar R, Pathan A, Nagaraj S, Kapare H, Giram P, Wavhale R. Polycaprolactone and its derivatives for drug delivery. Polymers for advanced technologies. 2023 Oct;34(10):3296-316.

9. Mahmoud BS, McConville C. Development and optimization of irinotecan-loaded PCL nanoparticles and their cytotoxicity against primary high-grade glioma cells. Pharmaceutics. 2021 Apr 13;13(4):541.

10. Chowdhury R, Sharma HK. Prostate cancer: Current and new drug delivery systems. In Drug Delivery Landscape in Cancer Research 2025 Jan 1 (pp. 351-373). Academic Press.

11. Ahmadi H, Haddadi‐Asl V. Curcumin‐loaded polycaprolactone nanoparticles prepared by emulsion evaporation stabilized with a pH‐responsive emulsifier. Polymer Engineering & Science. 2025 Apr 11.

12. Song B, Cho CW. Applying polyvinyl alcohol to the preparation of various nanoparticles. Journal of Pharmaceutical Investigation. 2024 May;54(3):249-66.

13. Herdiana Y, Wathoni N, Shamsuddin S, Joni IM, Muchtaridi M. Chitosan-based nanoparticles of targeted drug delivery system in breast cancer treatment. Polymers. 2021 May 24;13(11):1717.

14. Mohanty DL, Divya N, Zafar A, Warsi MH, Parida GR, Padhi P, Khalid M, Yasir M, Mujtaba MA. Development of etoricoxib-loaded mesoporous silica nanoparticles laden gel as vehicle for transdermal delivery: optimization, ex vivo permeation, histopathology, and in vivo anti-inflammatory study. Drug Development and Industrial Pharmacy. 2025 May 4;51(5):506-21.

15. Mohanty D, Gilani SJ, Zafar A, Imam SS, Kumar LA, Ahmed MM, Jahangir MA, Bakshi V, Ahmad W, Eltayib EM. Formulation and optimization of alogliptin-loaded polymeric nanoparticles: In vitro to in vivo assessment. Molecules. 2022 Jul 13;27(14):4470.

16. Panda N, Panda KC, Reddy A.V, Reddy G.V.S, Process Optimization, Formulation and Evaluation of Hydrogel {Guargum-Gpoly(Acrylamide)} Based Doxofylline Microbeads, Asian J Pharm Clin Res, Vol 7, Issue 3, 2014,60-65.

17. Chroni A, Mavromoustakos T, Pispas S. Curcumin-loaded PnBA-b-POEGA nanoformulations: A study of drug-polymer interactions and release behavior. International Journal of Molecular Sciences. 2023 Feb 27;24(5):4621.

18. Alik Kumar L, Pattnaik G, Satapathy BS, Mohanty D, Prasanth PA, Dey S, Debata J. Preparation and optimization of gemcitabine-loaded PLGA nanoparticle using Box-Behnken Design for targeting to brain: In vitro characterization, cytotoxicity and apoptosis study. Current Nanomaterials. 2024 Dec 1;9(4):324-38.

19. Aly GA, Sabra SA, Haroun M, Helmy MW, Moussa N. Bovine serum albumin nanoparticles encapsulating Dasatinib and Celecoxib for oral cancer: Preparation, characterization, and in-vitro evaluation. Naunyn-Schmiedeberg's Archives of Pharmacology. 2025 Feb 12:1-6.

20. Ali R, Huwaizi S, Alhallaj A, Al Subait A, Barhoumi T, Al Zahrani H, Al Anazi A, Latif Khan A, Boudjelal M. Newborn calf serum can induce spheroid formation in breast cancer KAIMRC1 cell line. Frontiers in Molecular Biosciences. 2021 Dec 24;8:769030.

21. Sánchez-Díez M, Romero-Jiménez P, Alegría-Aravena N, Gavira-O’Neill CE, Vicente-García E, Quiroz-Troncoso J, González-Martos R, Ramírez-Castillejo C, Pastor JM. Assessment of cell viability in drug therapy: IC50 and other new Time-Independent indices for evaluating chemotherapy efficacy. Pharmaceutics. 2025 Feb 13;17(2):247.

22. Mohanty D, Alsaidan OA, Zafar A, Dodle T, Gupta JK, Yasir M, Mohanty A, Khalid M. Development of atomoxetine-loaded NLC in situ gel for nose-to-brain delivery: optimization, in vitro, and preclinical evaluation. Pharmaceutics. 2023 Jul 20;15(7):1985.

23. Manning AN, Rowlands CE, Saindon H, Givens BE. Tuning the emulsion properties influences the size of poly (caprolactone) particles for drug delivery applications. The AAPS Journal. 2023 Oct 27;25(6):100.

24. Kitayama Y, Takigawa S, Harada A. Effect of poly (vinyl alcohol) concentration and chain length on polymer nanogel formation in aqueous dispersion polymerization. Molecules. 2023 Apr 15;28(8):3493.

25. Ishak KA, Annuar MS, Aris MH. Chain scission by ultrasonication of polycaprolactone with different initial molecular weight and concentration. Journal of Polymer Research. 2022 Apr;29(4):134.

26. Anastasia DS, Desnita R, Kurniawan US. Optimization of PVA concentration in the preparation of amlodipine besylate microparticles with ethyl cellulose polymer based on entrapment efficiency. Journal of Pharmaceutical Sciences and Research. 2023 Feb 1;15(2):1033-5.

27. Kolluru LP, Chandran T, Shastri PN, Rizvi SA, D’Souza MJ. Development and evaluation of polycaprolactone-based docetaxel nanoparticle formulation for targeted breast cancer therapy. Journal of Nanoparticle Research. 2020 Dec;22(12):372.

28. Mohammadi A, Nemati S, Mosaferi M, Abdollahnejhad A, Almasian M, Sheikhmohammadi A. Predicting the capability of carboxymethyl cellulose-stabilized iron nanoparticles for the remediation of arsenite from water using the response surface methodology (RSM) model: modeling and optimization. Journal of Contaminant Hydrology. 2017 Aug 1;203:85-92.

29. Filippov SK, Khusnutdinov R, Murmiliuk A, Inam W, Zakharova LY, Zhang H, Khutoryanskiy VV. Dynamic light scattering and transmission electron microscopy in drug delivery: A roadmap for correct characterization of nanoparticles and interpretation of results. Materials Horizons. 2023;10(12):5354-70.

30. Fan H, Jin Z. Hierarchical porous polycaprolactone microspheres generated via a simple pathway combining nanoprecipitation and hydrolysis. Chemical Communications. 2015;51(82):15114-7.

31. Manzari MT, Shamay Y, Kiguchi H, Rosen N, Scaltriti M, Heller DA. Targeted drug delivery strategies for precision medicines. Nature Reviews Materials. 2021 Apr;6(4):351-70.

32. Volkova TV, Drozd KV, Surov AO. Effect of polymers and cyclodextrins on solubility, permeability, and distribution of enzalutamide and apalutamide antiandrogens. Journal of Molecular Liquids. 2021 Jan 15;322:114937.

33. Li X, Peng X, Zoulikha M, Boafo GF, Magar KT, Ju Y, He W. Multifunctional nanoparticle-mediated combining therapy for human diseases. Signal Transduction and Targeted Therapy. 2024 Jan 1;9(1):1.

34. Abasian P, Shakibi S, Maniati MS, Nouri Khorasani S, Khalili S. Targeted delivery, drug release strategies, and toxicity study of polymeric drug nanocarriers. Polymers for Advanced Technologies. 2021 Mar;32(3):931-44.

35. Panda N, Reddy A.V, Reddy G.V.S, Panda KC; Effect of different grades of HPMC and Eudragit on drug release profile of Doxofylline sustained release matrix tablets and IVIVC studies. International Research Journal of Pharmacy, 6(8), (2015) 493-504.

Published

19-12-2025

How to Cite

Panda, Niranjan, et al. “Design and Development of Enzalutamide-Encapsulated PCL Nanoparticles for Prostate Cancer: A Box–Behnken Statistical Approach: Introduction, Materials & Methods, Characterization of Enzalutamide-Loaded Polycaprolactone Nanoparticles, Result and Discussion, Conclusion”. Asian Journal of Pharmaceutical and Clinical Research, vol. 19, no. 1, Dec. 2025, https://www.journals.innovareacademics.in/index.php/ajpcr/article/view/56565.

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