International Journal of Drug Delivery Technology
Volume 15, Issue 2

Recent Advances in the Formulation of Microspheres for the Effective Treatment of Rheumatoid Arthritis 

Mahua Bera1*, Suman Pattanayak1, Sovan Pattanaik2

1Haldia Institute of Pharmacy, Hatiberia, Purba Medinipur, West Bengal, India

2School of Pharmaceutical Science, Siksha O Anusandhan University, Bhubaneswar, Odisha, India 

Received: 21st Mar, 2025; Revised: 15th May, 2025; Accepted: 5th Jun, 2025; Available Online: 25th Jun, 2025 

ABSTRACT

Rheumatoid arthritis (RA) is an autoimmune disorder requiring targeted and sustained therapeutic interventions. Microspheres have emerged as a promising drug delivery system for rheumatoid management, offering improved bioavalability, reduce toxicity and enhance patient compliance. Recent advances in microspheres formulation have focused on developing biodegradable and biocompatible microspheres using natural and synthetic polymers. Novel fabrication technique such as microfluidics, electrospray and 3D printing has enabled the creation of uniform microspheres with controlled size, shape and composition. Additionally surface modification strategies have been explored to enhance microsphere targeting and cellular uptake. This abstract reviews the recent advances in microspheres formulation for RA management highlighting the potential of these systems to improve therapeutic outcomes and patient quality of life.

Keywords: microspheres, rheumatoid arthritis, drug delivery, biodegradable polymer, targeted therapy

How to cite this article: Mahua Bera, Suman Pattanayak, Sovan Pattanaik. Recent Advances in the Formulation of Microspheres for the Effective Treatment of Rheumatoid Arthritis. International Journal of Drug Delivery Technology. 2025;15(2):839-48.  doi: 10.25258/ijddt.15.2.60

REFERENCES

  1. Denkbaş EB, Kiliçay E, Birlikseven C, Öztürk E. Magnetic chitosan microspheres: preparation and characterization. International Journal of Drug Delivery Technology. 2002;50(3):225-232. doi:10.1016/S1381-5148(01)00115-8.
  2. Kawaguchi H. Functional polymer microspheres. International Journal of Drug Delivery Technology. 2000;25(8):1171-1210. doi:10.1016/S0079-6700(00)00024-1.
  3. Lacerda L, Parize AL, Fávere V, Laranjeira MCM, Stulzer HK. Development and evaluation of pH-sensitive sodium alginate/chitosan microparticles containing the antituberculosis drug rifampicin. Materials Science and Engineering: C, Materials for Biological Applications. 2014;39(1):161-167. doi:10.1016/J.MSEC.2014.01.054.
  4. Ma G, Yue H. Advances in uniform polymer microspheres and microcapsules: preparation and biomedical applications. Chinese Journal of Chemistry. 2020;38(9):911-923. doi:10.1002/CJOC.202000135.
  5. Ruan L, Su M, Qin X, Ruan Q, Lang W, Wu M, Chen Y, Lv Q. Progress in the application of sustained-release drug microspheres in tissue engineering. Materials Today Bio. 2022;16:100403. doi:10.1016/j.mtbio.2022.100403.
  6. Patil N, Wadd N, Thorat S, Upadhye SS. Microspheres: a novel drug delivery system. American Journal of PharmTech Research. 2020;10(4):1-10.
  7. Dhadde GS, Mali HS, Raut ID, Nitalikar MM, Bhutkar MA. A review on microspheres: types, method of preparation, characterization and application. Asian Journal of Pharmaceutical Technology. 2021;11(3):149-155. doi:10.52711/2231-5713.2021.00025.
  8. Azevedo MA, Bourbon AI, Vicente AA, Cerqueira MA. Alginate/chitosan nanoparticles for encapsulation and controlled release of vitamin B2. International Journal of Biological Macromolecules. 2014;71:141-146. doi:10.1016/j.ijbiomac.2014.05.036.
  9. Gautam A, Pal K. Gefitinib conjugated PEG-passivated graphene quantum dots incorporated PLA microspheres for targeted anticancer drug delivery. Heliyon. 2022;8(12):e12512. doi:10.1016/j.heliyon.2022.e12512.
  10. Ramasamy T, Ruttala HB, Shanmugam S, Umadevi SK, Subbiah K. Eudragit-coated aceclofenac-loaded pectin microspheres in chronopharmacological treatment of rheumatoid arthritis. Drug Delivery. 2013;20(2):65-77. doi:10.3109/10717544.2012.762434.
  11. Yadav M, Mandhare TA, Jadhav V, Otari K. A review on microspheres as a promising drug carrier. Journal of Drug Delivery and Therapeutics. 2024;14(1):1-10.
  12. Choi GW, Lee S, Kang DW, Kim JH, Cho HY. Long-acting injectable donepezil microspheres: formulation development and evaluation. Journal of Controlled Release. 2021;335:58-67.
  13. Qiu S, Shi Y, Zang H, Wang Q, Fu X, Shen H, Mo F, Zhang Y, Chen X, Zhou J, Li L, Lin G. Preparation of injectable double-layer microspheres for the long-term treatment of osteoarthritis. Available at SSRN. 2022;4233584.
  14. Ruvinov E, Leor J, Cohen Smadar S. The effects of controlled HGF delivery from an affinity-binding alginate biomaterial on angiogenesis and blood perfusion in a hindlimb ischemia model. Biomaterials. 2010;31(16):4573-4582. doi:10.1016/J.BIOMATERIALS.2010.02.026.
  15. Parvathaneni M, Awol AK, Kumari M, Lan K, Lingam M. Application of artificial intelligence and machine learning in drug discovery and development. Journal of Drug Delivery and Therapeutics. 2023;13(1):151-158. doi:10.22270/jddt.v13i1.5867.
  16. Dasari V, Shaikh A, Sisodiya D, Bhargava T, Dangi R, Nagwe S, Khan SL, Siddiqui FA. Stability study of mucoadhesive microsphere containing nateglinide by using biodegradable polymer chitosan. Journal of Pharmaceutical Research International. 2021;33(47A):866-872. doi:10.9734/jpri/2021/v33i47A33086.
  17. Kim DH, Huegel J, Taylor BL, Nuss CA, Weiss SN, Soslowsky LJ, Mauck RL, Kuntz AF. Biocompatibility and bioactivity of an FGF-loaded microsphere-based bilayer delivery system. Acta Biomaterialia. 2020;105:213-225.
  18. Slomkowski S, Basinska TT, Miksa BB. New types of microspheres and microsphere-related materials for medical diagnostics. Polymers for Advanced Technologies. 2002;13(10-12):905-918. doi:10.1002/PAT.283.
  19. Sapra A, Hm H, Amin S, Kelsi F. Development of mucoadhesive microspheres for intranasal delivery of fluconazole as an alternative treatment of cryptococcal meningitis infection in patients. Advanced Drug Delivery Reviews. 2024;200:114123.
  20. Mitragotri S, Yoo JW. Designing micro- and nano-particles for treating rheumatoid arthritis. Archives of Pharmacal Research. 2011;34(11):1887-1897.
  21. Cush JJ. Rheumatoid arthritis: early diagnosis and treatment. Medical Clinics of North America. 2021;105(2):355-365. doi:10.1016/J.MCNA.2020.10.006.
  22. Wang G, Zhang XA, Kapilevich L, Hu M. Recent advances in polymeric microparticle-based drug delivery systems for knee osteoarthritis treatment. Frontiers in Bioengineering and Biotechnology. 2023;11:1290870.
  23. Lee JE, Kim IJ, Cho MS, Lee J. A case of rheumatoid vasculitis involving hepatic artery in early rheumatoid arthritis. Journal of Korean Medical Science. 2017;32(7):1207-1210. doi:10.3346/jkms.2017.32.7.1207.
  24. Miyazaki Y, Glass L, Triplitt C, et al. Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in type II diabetic patients. Diabetologia. 2001;44(12):2210–2219. doi: 10.1007/s001250100020.
  25. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. New England Journal of Medicine. 2011;365(23):2205-2219. doi:10.1056/NEJMRA1004965.
  26. Chaudhari K, Rizvi S, Syed BA. Rheumatoid arthritis: current and future trends. Nature Reviews Drug Discovery. 2016;15(5):305-319.
  27. Chopra A. Epidemiology of rheumatic musculoskeletal disorders in the developing world. Best Practice & Research Clinical Rheumatology. 2008;22(4):583-604.
  28. Picerno V, Ferro F, Adinolfi A, Valentini E, Tani C, Alunno A. One year in review: the pathogenesis of rheumatoid arthritis. Clinical and Experimental Rheumatology. 2015;33(4):551-558.
  29. Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Research. 2018;6(1):15. doi:10.1038/s41413-018-0016-9.
  30. Pradeepkiran JA. Insights of rheumatoid arthritis risk factors and associations. Journal of Translational Autoimmunity. 2019;2:100012. doi:10.1016/j.jtauto.2019.100012.
  31. Hynnekleiv L, Magno M, Vernhardsdottir RR, Moschowits E, Tønseth KA, Dartt DA, Vehof J, Utheim TP. Hyaluronic acid in the treatment of dry eye disease. Acta Ophthalmologica. 2022;100(8):844-860. doi:10.1111/aos.15159.
  32. Aletaha D. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018.
  33. Abdelhafiz D, Baker T, Glascow DA, Abdelhafiz A. Biomarkers for the diagnosis and treatment of rheumatoid arthritis – a systematic review. Postgraduate Medicine. 2023;135(3):214-223. doi:10.1080/00325481.2022.2052626.
  34. Kourilovitch M, Galarza-Maldonado C, Ortiz-Prado E. Diagnosis and classification of rheumatoid arthritis. Journal of Autoimmunity. 2014.
  35. Radu AF, Bungau SG. Management of rheumatoid arthritis: an overview. Cells. 2021;10(11):2857. doi:10.3390/CELLS10112857.
  36. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. New England Journal of Medicine. 2011;365(23):2205-2219. doi:10.1056/NEJMRA1004965.
  37. Guo Q, Wang Y, Xu D, Nossent J, Pavlos N, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Research. 2018. doi:10.1038/s41413-018-0016-9.
  38. Ferreira-Silva M, Faria-Silva C, Viana Baptista P, Fernandes E, Fernandes AR, Corvo ML, Álvarez R, González Rodríguez ML. Liposomal nanosystems in rheumatoid arthritis. Pharmaceutics. 2021. doi:10.3390/pharmaceutics13040454.
  39. Olson AL, Swigris JJ, Sprunger DB, Fischer A, Fernandez-Perez ER, Solomon J, Murphy J, Cohen M, Raghu G, Brown KK. Rheumatoid arthritis–interstitial lung disease–associated mortality. American Journal of Respiratory and Critical Care Medicine. 2011;183(3):372-378. doi:10.1164/rccm.201004-0622OC.
  40. Crowson CS, Liao KP, Davis JM III, Solomon DH, Matteson EL, Knutson KL, Hlatky MA, Gabriel SE. Rheumatoid arthritis and cardiovascular disease. American Heart Journal. 2013. doi:10.1016/j.ahj.2013.07.010.
  41. Gremese E, Ferraccioli G. The metabolic syndrome: the crossroads between rheumatoid arthritis and cardiovascular risk. Autoimmunity Reviews. 2011.
  42. Majithia V, Geraci SA. Rheumatoid arthritis: diagnosis and management. American Journal of Medicine. 2007;120(11):936-939. doi:10.1016/j.amjmed.2007.04.005.
  43. Calderón MF. Rheumatoid arthritis, its diagnostic approach and how to treat it. International Journal of Medical Science and Clinical Research Studies. 2022;2(4). doi:10.47191/ijmscrs/v2-i4-05.
  44. Avramidis GP, Avramidou MP, Papakostas GA. Rheumatoid arthritis diagnosis: deep learning vs. humane. Applied Sciences. 2022;12(1). doi:10.3390/app12010010.
  45. Weddell J, Hider S. Diagnosis and management of rheumatoid arthritis. Prescriber. 2021;84(11):1245-1252. doi:10.1002/psb.1945.
  46. Conte U, Maggi L, Colombo P, La Manna A. Multi-layered hydrophilic matrices as constant release devices (Geomatrix® systems). Journal of Controlled Release. 1993;26(1):39–47. doi: 10.1016/0168-3659(93)90185-2.
  47. Kim EJ, Seo JB, Yu JS, Lee S, Lim JS, Choi JU, Lee CM, Rashan L, Kim KH, Cho YC. Anti-inflammatory effects of a polyphenol, catechin-7,4′-O-digallate, from Woodfordia uniflora by regulating NF-κB signaling pathway in mouse macrophages. Pharmaceutics. 2021. doi:10.3390/pharmaceutics13030408.
  48. Jaiswal H, Ansari MT, Mahmood T, Ahsan F, Ansari VA, Ahmad U. Aceclofenac loaded microspheres: formulation and evaluation of novel preprogrammed drug delivery for the treatment of arthritis. Intelligent Pharmaceuticals. 2024;2(1):69-82. doi:10.1016/j.ipha.2023.10.010.
  49. Yadav R, Bhowmick M, Rathi V, Rathi J. Design and characterization of floating microspheres for rheumatoid arthritis. Journal of Drug Delivery and Therapeutics. 2019;9(2-s):76-81. doi:10.22270/jddt.v9i2-s.2463.
  50. Yu Y, Wang Z, Ding Q, Yu X, Yang Q, Wang R, Fang Y, Qi W, Liao J, Hu W, Zhu Y, Fernandes I, Jozala AF, Vandamme T. The preparation of a novel poly(lactic acid)-based sustained H₂S releasing microsphere for rheumatoid arthritis alleviation. Pharmaceutics. 2021;13(5):742. doi:10.3390/pharmaceutics13050742.
  51. Natarajan V, Krithica N, Madhan B, Sehgal PK. Formulation and evaluation of quercetin polycaprolactone microspheres for the treatment of rheumatoid arthritis. Journal of Pharmaceutical Sciences. 2011.
  52. Li Y, Zhu H, Liu R, Zhao Y, Sun L. Hierarchical microcarriers loaded with peptide dendrimer‐grafted methotrexate for rheumatoid arthritis treatment. Small Science. 2024;4(1). doi:10.1002/smsc.202300097.
  53. Shah R, Bhattacharya S. Preparation and physical characterization of methotrexate encapsulated poly (N-methyl glycine) microspheres for the rheumatoid arthritis treatment option. Results in Chemistry. 2023.
  54. Jayakrishna P, Mahendra GN. Design of 16-bit adder, multiplier, and ALU using reversible logic gates. International Journal of Novel Research and Development. 2023;8(5).
  55. Du Y, Li C, Zhang Y, Xiong W, Wang F, Wang J, Zhang Y, Deng L, Li X, Chen W, Cui W. In situ-activated phospholipid-mimic artemisinin prodrug via injectable hydrogel nano/microsphere for rheumatoid arthritis therapy. Research. 2022. doi:10.34133/research.0003.
  56. Thadanki ML. Formulation and evaluation of sustained release saxagliptin microspheres by ionotropic gelation method. International Journal of Bioassays. 2017;6(3):5328. doi:10.21746/ijbio.2017.03.0010.
  57. Bazzo GC, Macedo AT, Crenca JP, Silva VE, Pereira EM, Zétola M, Pezzini BR. Microspheres prepared with biodegradable PHBV and PLA polymers as prolonged-release system for ibuprofen: In vitro drug release and in vivo evaluation. Brazilian Journal of Pharmaceutical Sciences. 2012;48(4):773-780. doi:10.1590/S1984-82502012000400021.
  58. Pawashe PM, Patil SKS, Naikwade NS. Prochlorperazine maleate loaded sustained release floating microspheres prepared by ionotropic gelation technique: morphology and release characteristics. Research Journal of Pharmacy and Technology. 2019;12(8):3866. doi:10.5958/0974-360X.2019.00664.4.
  59. Bera M, Pattanayak S, Kanthal LK, Mahapatra L, Pani A, Jana S, Pal S, Das S, Maity A, Maity D. Preparation and evaluation of aceclofenac microsphere containing natural gum. Research Journal of Pharmacy and Dosage Forms Technology. 2023:163-168. doi:10.52711/0975-4377.2023.00027.
  60. Li M, Rouaud O, Poncelet D. Microencapsulation by solvent evaporation: state of the art for process engineering approaches. International Journal of Pharmaceutics. 2008;363(1–2):26-39. doi:10.1016/j.ijpharm.2008.07.018.
  61. Li G, He Y, Han W, Yu Y, Zhu L, Si T, Sun Y. An improved solvent evaporation method to produce poly (lactic acid) microspheres via foam-transfer. International Journal of Biological Macromolecules. 2021;172:114-123. doi: 10.1016/j.ijbiomac.2021.01.031.
  62. Mutagond C, Kolageri S, Katagaon SB. Formulation and evaluation of microspheres of ramipril. Journal of Drug Delivery and Therapeutics. 2022.
  63. O’Donnell PB, McGinity JW. Preparation of microspheres by the solvent evaporation technique. Advanced Drug Delivery Reviews. 1997;28:25-42.
  64. Yang YY, Chia HH, Chung TS. Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction. Journal of Controlled Release. 2000;69:81-96.
  65. Dastidar DG, Saha S, Chowdhury M. Porous microspheres: synthesis, characterisation and applications in pharmaceutical & medical fields. International Journal of Pharmaceutics. 2018;548(1):34-48. doi: 10.1016/j.ijpharm.2018.06.015.
  66. Varghese R, Nair NM, Lekshmi AM, Nair MM, Abraham L, Aniyan N, Shajan A. Floating microspheres as novel drug delivery system for arthritis. Asian Journal of Pharmaceutical Research and Development. 2016;4(1):1-5.
  67. Wang LY, Ma GH, Su ZG. Preparation of uniform sized chitosan microspheres by membrane emulsification technique and application as a carrier of protein drug. Journal of Controlled Release. 2005;106(1-2):62-75. doi: 10.1016/j.jconrel.2005.04.005.
  68. Wang AJ, Lu YP, Sun RX. Recent progress on the fabrication of hollow microspheres. Materials Science and Engineering A. 2007;3(1):120-300.
  69. Raval JA, Patel JK, Patel MM. Formulation and in vitro characterization of spray-dried microspheres of amoxycillin. Acta Pharmaceutica. 2010. doi: 10.2478/v10007-010-0034-7.
  70. Zhang Z, Li L, Sun D, Wang M, Shi J, Yang D, Wang L, Zou S. Preparation and properties of chitosan‐based microspheres by spray drying. Food Science & Nutrition. 2020;8(4):1933-1941. doi: 10.1002/fsn3.1479.
  71. He P, Davis SS, Illum L. Chitosan microspheres prepared by spray drying. International Journal of Pharmaceutics. 1999; 3(2):75-90.