DESIGN CHARACTERIZATION OPTIMIZATION OF LENALIDOMIDE-LOADED BOVINE SERUM ALBUMIN NANOPARTICLES FOR MYELOMA THERAPY

Authors

  • SAMEENA BEGUM Department of Pharmacy, Chaitanya Deemed to be University, Warangal-506001, Telangana https://orcid.org/0009-0001-5148-1241
  • NIRANJAN PANDA School of Pharmacy, The Neotia University, 24 Parganas (South), West Bengal-743368, India https://orcid.org/0000-0002-1821-7326
  • CH. PRAVEENA Department of Pharmacy, Chaitanya Deemed to be University, Warangal-506001, Telangana, India

DOI:

https://doi.org/10.22159/ijap.2026v18i1.55623

Keywords:

BSA, Nanoparticle, Myeloma, Optimization, Lenalidomide

Abstract

Objective: The present investigation focuses on the formulation and optimization of lenalidomide (LD)-loaded bovine serum albumin (BSA) nanoparticles (NPs) using the desolvation method. Box-Behnken design (BBD) was implemented to optimize the formulation.

Methods: The desolvation technique was employed to synthesize BSA-NPs encapsulating LD and characterized by particle size analysis, zeta potential, and transmission electron microscopy (TEM) analysis.

Results: The findings confirmed that the uniform spherical NPs were formed below 200 nm. Particle size found in the range of 110.9±13.02nm to 182.8±10.33nm, entrapment efficiency (EE) found between 60.1±9.01% and 94.80±9.14% and zeta potential-15.3±0.21mV to -29.7 ±0.12mV. A sudden burst release of approximately 55.68% was observed within 4 hours from optimized LD BSA NPs (Opt-LD-BSA-NPs), followed by a slower release over 24 hours. In vitro, cytotoxicity assays demonstrated selective toxicity against U266 cancer cells. The Opt-LD-BSA-NPs exhibited a significantly lower half-maximal inhibitory concentration (IC50) of 29.70%, indicating enhanced cytotoxic efficacy. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses indicated successful drug entrapment and a transition of LD from a crystalline to an amorphous form. The area under curve (AUC) for Opt-LD-BSA-NPs was found to be 22.47 µg/ml/hr, which is 3 times more than the pure LD suspension (6.3025 µg/ml/hr). It revealed enhanced bioavailability.

Conclusion: These findings underscore the potential of BSA-based nanocarriers to enhance the solubility, stability, and therapeutic efficacy of hydrophobic anticancer agents, such as LD.

References

1. Al-Ostoot FH, Salah S, Khanum SA. An Overview of Cancer Biology, Pathophysiological Development, and Its Treatment Modalities: Current Challenges of Cancer Anti-Angiogenic Therapy. Cancer Investigation. 2024 Aug 8;42(7):559-604.doi.org/10.1080/07357907.2024.2361295 ,PMID: 38874308

2. Sriharikrishnaa S, Suresh PS, Prasada K S. An introduction to fundamentals of cancer biology. In Optical Polarimetric Modalities for Biomedical Research 2023 Jul 23 (pp. 307-330). Cham: Springer International Publishing.doi.org/10.1007/978-3-031-31852-8_11

3. Sobti RC, Gosipatala SB, Sharma M, Reddy P, Khalko RK, Kaur T, Thakur M. Types of Cancers, Epidemiology, and Molecular Insights. In Handbook of Oncology: From Basic to Clinical Sciences 2023 Oct 10 (pp. 1-36). Singapore: Springer Nature Singapore. doi:10.1007/978-981-99-2196-6_1-1

4. Ahmad I, Jasim SA, Sharma MK, S RJ, Hjazi A, Mohammed JS, Sinha A, Zwamel AH, Hamzah HF, Mohammed BA. New paradigms to break barriers in early cancer detection for improved prognosis and treatment outcomes. The Journal of Gene Medicine. 2024 Aug;26(8):e3730.10.1002/jgm.3730.

5. Ahmed MB, Alghamdi AA, Islam SU, Ahsan H, Lee YS. The complex roles of DNA repair pathways, inhibitors, hyperthermia, and contact inhibition in cell cycle halts. Mini-Reviews in Medicinal Chemistry. 2023 Mar 1;23(5):514-29.doi: 10.2174/1389557522666220826141837

6. Mazingi D, Lakhoo K. Cancer Development and Progression and the “Hallmarks of Cancer”. In Pediatric Surgical Oncology 2023 Jun 14 (pp. 1-15). Cham: Springer International Publishing 10.1007/978-3-030-71113-9_23-1.

7. Wang H, Guo M, Wei H, Chen Y. Targeting p53 pathways: Mechanisms, structures and advances in therapy. Signal transduction and targeted therapy. 2023 Mar 1;8(1):92.doi.org/10.1038/s41392-023-01347-1

8. Wang Y, Iqbal H, Ur-Rehman U, Zhai L, Yuan Z, Razzaq A, Lv M, Wei H, Ning X, Xin J, Xiao R. Albumin-based nanodevices for breast cancer diagnosis and therapy. Journal of Drug Delivery Science and Technology. 2023 Jan 1;79:104072.10.1016/j.jddst.2022.104072

9. Behera S, Mohanty P, Dash PP, Mohapatra P, Shubhadarshinee L, Behura R, Barick AK, Mohapatra P, Jali BR. Selective binding of bovine serum albumin (BSA): a Comprehensive Review. Biointerface Research in Applied Chemistry. 2023;13:555. 10.33263/BRIAC136.555

10. Mardikasari SA, Katona G, Csóka I. Serum albumin in nasal drug delivery systems: exploring the role and application. Pharmaceutics. 2024 Oct 11;16(10):1322.10.3390/pharmaceutics16101322.

11. Lawal RA, Banjoko O, Ndulue C, Adebeshin ST, Sharif A, Ighodaro OE, Olusoji R, Odusanya B, El-Hamdi NS, Ndulue CC, Adebeshin S. Improved Side Effect Profile of Alternate-Day Dosing of Lenalidomide. Cureus. 2024 Mar 1;16(3).doi: 10.7759/cureus.55317.

12. Banchi M, Cox MC, Bocci G. Metronomic chemotherapy in hematology: Lessons from preclinical and clinical studies to build a solid rationale for future schedules. Cancer Letters. 2024 Jun 1;591:216900.10.1016/j.canlet.2024.216900

13. Takahashi Y, Nagamine A, Kaneta A, Yashima H, Obayashi K, Araki T, Yamamoto K. Risk of exposure of patients’ family members to lenalidomide at home. European Journal of Hospital Pharmacy. 2024 Nov 1;31(6):555-9. Doi: 10.1136/ejhpharm-2022-003632.

14. Nadeem O, Ailawadhi S, Khouri J, Williams L, Catamero D, Maples K, Berdeja J. Management of adverse events associated with pomalidomide-based combinations in patients with relapsed/refractory multiple myeloma. Cancers. 2024 Feb 29;16(5):1023.doi: 10.3390/cancers16051023.

15. Screen MA, Tomkinson G, McCabe JF, Askin S, Mahon CS, Wilson MR, Steed JW. Designing lenalidomide cocrystals with an extended-release profile for improved pulmonary drug delivery. New Journal of Chemistry. 2025;49(16):6535-43.doi.org/10.1039/D5NJ00425J

16. Gupta A, Moorkoth S, Dhas N. Central composite design aided optimization and validation of developed an eco-friendly HPLC method for the quantification of Lenalidomide loaded mesoporous silica nanoparticles. Journal of Applied Pharmaceutical Science. 2024 Nov 25;15(1):089-101.DOI: 10.7324/JAPS.2024.189998

17. Delche NA, Kheiri R, Nejad BG, Sheikhi M, Razavi MS, Rahimzadegan M, Salmasi Z. Recent progress in the intranasal PLGA-based drug delivery for neurodegenerative diseases treatment. Iranian Journal of Basic Medical Sciences. 2023;26(10):1107. doi: 10.22038/IJBMS.2023.70192.15264

18. Kono Y, Sugaya T, Yasudome H, Ogiso H, Ogawara KI. Preparation of stable and monodisperse paclitaxel-loaded bovine serum albumin nanoparticles via intermolecular disulfide crosslinking. Biochemistry and Biophysics Reports. 2024 Jul 1;38:101713.doi: 10.1016/j.bbrep.2024.101713.

19. Hsu WH, Ku CL, Lai YR, Wang SS, Chou SH, Lin TH. Developing targeted drug delivery carriers for breast cancer using glutathione-sensitive doxorubicin-coupled glycated bovine serum albumin nanoparticles. International Journal of Biological Macromolecules. 2023 Sep 30;249:126114. doi: 10.1016/j.ijbiomac.2023.126114.

20. Yang S, Diao Y, Hang L, Qu H, Fang L, Guo W, Wen H, Iu K, Jiang G, Shao L, Li Q. BSA@ IR780-loaded mesoporous polydopamine nanoparticles with enhanced photostability for multimodal imaging and photothermal therapy of tumors. Nanoscale Advances. 2025;7(8):2182-94.doi.org/10.1039/D5NA00008D

21. Hasan HJ, Ghareeb MM, Hasan Sr H. Optimizing Desolvation Conditions for Glutathione-Cross-Linked Bovine Serum Albumin Nanoparticles: Implication for Intravenous Drug Delivery. Cureus. 2024 Sep 16;16(9).doi: 10.7759/cureus.69514. eCollection 2024 Sep.

22. Behram T, Pervez S, Nawaz MA, Ahmad S, Jan AU, Rehman HU, Ahmad S, Khan NM, Khan FA. Development of pectinase-based nanocatalyst by immobilization of pectinase on magnetic iron oxide nanoparticles using glutaraldehyde as a crosslinking agent. Molecules. 2023 Jan 3;28(1):404. Doi: 10.3390/molecules28010404

23. Maiti R, Panigrahi S, Yin T, Huo M. Bovine serum albumin nanoparticles constructing procedures on anticancer activities. Int J Adv Res Biol Sci. 2018;5(4):226-39.DOI: 10.22192/ijarbs

24. Jena S, Aksan A. Effect of high DMSO concentration on albumin during freezing and vitrification. RSC Advances. 2017;7(69):43611-20.doi.org/10.1039/C7RA07556A

25. Jahanshahi M, Najafpour G, Rahimnejad M. Applying the Taguchi method for optimized fabrication of bovine serum albumin (BSA) nanoparticles as drug delivery vehicles. African Journal of Biotechnology. 2008;7(4).

26. Karri VV, Dhandapani NV, Mannemala SS, Radhakrishna K, Mulukutla S, Sudunagunta D. Ameliorating the antitumor activity of lenalidomide using PLGA nanoparticles for the treatment of multiple myeloma. Brazilian Journal of Pharmaceutical Sciences. 2017 Jun 22;53:e15185. https://doi.org/10.1590/s2175-97902017000215185

27. Panda N, Charan Panda K, Reddy AV, Reddy GVS. Process optimization, formulation and evaluation of hydrogel {guar gum-g-poly(acrylamide)} based doxofylline microbeads. Asian J Pharm Clin Res. 2014 Jul 1;7(3):60-5.

28. Mansour A, Fytory M, Ahmed OM, Rahman FE, El-Sherbiny IM. In-vitro and in-vivo assessment of pH-responsive core-shell nanocarrier system for sequential delivery of methotrexate and 5-fluorouracil for the treatment of breast cancer. International Journal of Pharmaceutics. 2023 Dec 15;648:123608. doi: 10.1016/j.ijpharm.2023.123608. Epub 2023 Nov 14.

29. Niranjan, P.; Reddy, A.V.; Reddy, G.V.S.; Panda, K.C. Formulation, design, and in vitro evaluation of zolmitriptan immediate release tablets using Primojel and Ac-Di-Sol. J. Pharm. Sci. Res. 2015, 7, 545–553.

30. Sharma V, Sundaramurthy A. Surface modification of bare copper grids with charged polymers: A simple alternative for carbon-coated copper grids in transmission electron microscopy. Materials Letters. 2022 Feb 1;308:131204.doi.org/10.1016/j.matlet.2021.131204

31. Silva F, Sitia L, Allevi R, Bonizzi A, Sevieri M, Morasso C, Truffi M, Corsi F, Mazzucchelli S. Combined method to remove endotoxins from protein nanocages for drug delivery applications: the case of human ferritin. Pharmaceutics. 2021 Feb 6;13(2):229.doi: 10.3390/pharmaceutics13020229.

32. Terzi H, Altun A, Şencan M. In vitro comparison of the cytotoxic effects of statins on U266 myeloma cell line. Indian Journal of Medical Research. 2019 Dec 1;150(6):630-4.doi: 10.4103/ijmr.IJMR_672_18.

33. Niranjan P, Reddy V, Reddy G, Panda K. Effect of different grades of HPMC and Eudragit on drug release profile of doxofylline sustained release matrix tablets and IVIVC studies. Int Res J Pharm. 2015;6:493–504.

34. Tanjung YP, Dewi MK, Gatera VA, Barliana MI, Joni IM, Chaerunisaa AY. Factors affecting the synthesis of bovine serum albumin nanoparticles using the desolvation method. Nanotechnology, Science, and Applications. 2024 Dec 31:21-40.doi: 10.2147/NSA.S441324.

35. Wallerstein J, Akke M. Minute additions of DMSO affect protein dynamics measurements by NMR relaxation experiments through significant changes in solvent viscosity. ChemPhysChem. 2019 Jan 21;20(2):326-32. DOI: 10.1002/cphc.201800626

36. Magalhães IS, Maurílio KB, de Souza DA, Tribst AA, Leite Júnior BR. Application of Roasting, Ultrasound, and High-Shear Dispersion in Pea Protein Extraction: Yield Parameters, Macrostructural Characteristics, and Technical-Functional Properties. Food and Bioprocess Technology. 2025 Apr 21:1-4.DOI:10.1007/s11947-025-03852-3

37. Spada A, Emami J, Tuszynski JA, Lavasanifar A. The uniqueness of albumin as a carrier in nano drug delivery. Molecular pharmaceutics. 2021 Mar 31;18(5):1862-94. Doi: 10.1021/acs.molpharmaceut.1c00046

38. Shalmani AA, Wang A, Ahmed Z, Sheybanifard M, Mihyar R, Buhl EM, Pohl M, Hennink WE, Kiessling F, Metselaar JM, Shi Y. Tunable polymeric micelles for taxane and corticosteroid co-delivery. Drug Delivery and Translational Research. 2024 Oct;14(10):2642-54.doi: 10.1007/s13346-023-01465-x.

39. Zaibudeen AW, Philip J. Adsorption of bovine serum albumin at oil-water interface in the presence of polyelectrolytes and nature of interaction forces. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2019 Apr 5;566:38-47.doi.org/10.1016/j.colsurfa.2019.01.014

40. Wilson BK, Prud'homme RK. Nanoparticle size distribution quantification from transmission electron microscopy (TEM) of ruthenium tetroxide stained polymeric nanoparticles. Journal of Colloid and Interface Science. 2021 Dec 15;604:208-20. doi: 10.1016/j.jcis.2021.04.081. Epub 2021 Apr 20.

41. Hemangi Amrutbhai Virani, Mitul Sanjaybhai Upadhyay, Piyush Mansinh Pargi, Ashish P. Anovadiya. Evaluation Of Hypolipidemic Activity Of Opuntia Elatior Fruit Juice In High-Fat Diet-Induced Hyperlipidemia In Wistar Albino Rats. Asian J Pharm Clin Res [Internet]. 2025 Jul. 7 [cited 2025 Jul. 25];18(7):240-4.

Published

27-10-2025

How to Cite

BEGUM, S., PANDA, N., & PRAVEENA, C. (2025). DESIGN CHARACTERIZATION OPTIMIZATION OF LENALIDOMIDE-LOADED BOVINE SERUM ALBUMIN NANOPARTICLES FOR MYELOMA THERAPY. International Journal of Applied Pharmaceutics, 18(1). https://doi.org/10.22159/ijap.2026v18i1.55623

Issue

Section

Original Article(s)

Similar Articles

<< < 3 4 5 6 7 > >> 

You may also start an advanced similarity search for this article.