Prolongation of Anti-Inflammatory Activity of Glucocorticosteroids Encapsulated in Large Oligolamellar Liposomes in Treatment of Arthritis in Rabbits

ORIGINAL ARTICLE
O.A. Rosenberg, PhD, ScD; A.A. Seiliev, PhD; A.Ed. Shulga; A.G. Zhuikov, PhD; V.A. Volchkov, PhD, ScD

Russian Research Center of Radiology and Surgery Technologies, St. Petersburg, Russia.

*Corresponding author: Prof. Oleg Rosenberg, PhD, ScD.  Department of Medical Biotechnology of Russian Research Center of Radiology and Surgery Technologies, St. Petersburg, Russia. E-mail: rozenberg@biosurf.ru

Published: June 16, 2017.  doi: 10.21103/Article7(2)_OA9

Abstract: 

Background: Liposomes have been shown to be an effective targeted drug delivery system used to decrease side effects of glucocorticosteroids in the treatment of rheumatoid arthritis.
Materials and Results: Experimental arthritis was induced in rabbits by a single intra-articular administration into the knee joint of poly-D-lysine (molecular weight, 175 kDa) and hyaluronic acid (7.5 mg per administration). To determine temperature readings over the joint a standard radiator was used with a temperature of 32 0C. Large oligolamellar liposomes from different phospholipidsand and cholesterol containing hydrocortisone acetate in lipid phase and prednisolone hemisuccinate in water phase were used.
Conclusion: Intra-articular administration of the water-soluble prednisolone hemisuccinate  (0.125 mg) and the lipid-soluble hydrocortisone acetate (0.125 mg) into the knee joint in the aqueous and lipid phases of large oligolamellar TSL (DPPC + 20 mole % cholesterol) prolongs the anti-inflammatory effect produced by glucocorticoids by 7–8 days compared to 1 day for free glucocorticosteroids at a total dose of 2.5 mg and 2 days for phosphatidylcholine-cholesterol liposomes at a total dose of 0.25 mg in rabbits with aseptic arthritis.

Keywords: 
aseptic arthritis ● thermosensitive liposomes ● glucocorticosteroids ● anti-inflammatory activity
References: 
  1. Massarotti EM. Clinical and patient-reported outcomes in clinical trials of abatacept in the treatment of rheumatoid arthritis. Clin Ther. 2008;30(3):429-42. doi: 10.1016/j.clinthera.2008.03.002.
  2. Kapoor B, Singh SK, Gulati M, Gupta R, Vaidya  Y. Application of liposomes in treatment of rheumatoid arthritis: quo vadis. ScientificWorldJournal. 2014;2014:978351. doi: 10.1155/2014/978351.
  3. Curtis JR, Singh JA. Use of biologics in rheumatoid arthritis: current and emerging paradigms of care. Clin Ther. 2011;33(6):679–707. doi: 10.1016/j.clinthera.2011.05.044.
  4. Davidenkova EF, Ternova NK, Rozenberg OA, Noskin LA, Loshakova LV. [Relation between the prolongation of the anti-inflammatory activity of liposome-encapsulated hydrocortisone and liposome composition in experimental arthritis]. Biull Eksp Biol Med. 1984;97(6):656-8. [Article in Russian].
  5. Ivkov VG, Berestovsky GN. Dynamic structure of the lipid bilayer. Moscow: Nauka; 1981.
  6. Dingl JT, Gordon JL, Hazelman BL, Knight CG, Page Thomas DP, Phillips NC, et al. Novel treatment for joint inflammation. Nature. 1978; 271(5643):372–3.
  7. Szoka F Jr, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA. 1978; 75(9):4194–8.
  8. Antonov VF, Anosov AA, Norik VP, Korepanova EA, Smirnova EY. Electrical capacitance of lipid bilayer membranes of hydrogenated egg lecithin at the temperature phase transition. Eur Biophys J. 2003 Mar;32(1):55-9.
  9. Rozenberg OA, Bekreneva VIu, Loshakova LV, Rezvaia SP, Davidenkova EF. [Specificity of liposome uptake from target cell lipids]. Biull Eksp Biol Med. 1984;97(6):670-2. [Article in Russian]

The fully formatted PDF version is available.
Download Article
International Journal of Biomedicine. 2017;7(2):131-134. ©2017 International Medical Research and Development Corporation. All rights reserved.