Topical gel formulation and stability assessment of platelet lysate based on turbidimetric method

Document Type : Research(Original) Article

Authors

1 Center for Drug Delivery in Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

3 School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Platelet-rich growth factors have attracted attentions of scientists and clinical practitioners who are involved in wound healing and regenerative medicine extensively, according to their unprecedented potential of promoting and catalyzing healing process. Platelet-rich growth factors are cost-benefit, available and are more stable than recombinant human growth factors. These appealing characteristics have converted PRGF to one of the popular candidate for treatment of variety of wounds. According to these valuable properties, we decided to formulate and assess the effect of different excipients on the stability of such valuable protein based formulations. Different excipients have been chosen according to their effectiveness on the stability of proteins and their application in the other similar formulations. The stabilizing effect of excipients was evaluated by measuring heat-induced aggregation of growth factors by turbidimetric assay. Glycerol, glycine and dextrose were chosen as stabilizing excipient for these formulations. The results show that dextrose has more stabilizing effect on prevention of heat induced aggregation of the platelet lysate growth factors than glycerol and glycine. All of the formulations also contained antioxidant, chelating agents, preservative and carbopol 934 in order to form appropriate gel

  1. Gobbi G, Vitale M. Platelet-Rich Plasma Preparations for Biological Therapy: Applications and Limits. Operative Techniques in Orthopaedics. 2012;22(1):10-5.
  2. Mescher AL. Junqueira's Basic Histology: Text & Atlas: Mcgraw-hill medical New York; 2010.
  3. Andia I, Sanchez M, Maffulli N. Basic science: molecular and biological aspects of platelet-rich plasma therapies. Operative Techniques in Orthopaedics. 2012;22(1):3-9.
  4. Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma from basic science to clinical applications. The American journal of sports medicine. 2009;37(11):2259-72.
  5. Wroblewski AP, Mejia HA, Wright VJ. Application of platelet-rich plasma to enhance tissue repair. Operative Techniques in Orthopaedics. 2010;20(2):98-105.
  6. Enoch S, Leaper DJ. Basic science of wound healing. Surgery (Oxford). 2008;26(2):31-7.
  7. Everts PA, Knape JT, Weibrich G, Schonberger J, Hoffmann J, Overdevest EP, et al. Platelet-rich plasma and platelet gel: a review. Journal of ExtraCorporeal Technology. 2006;38(2):174.
  8. Man D, Plosker H, Winland-Brown JE. The use of autologous platelet-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin glue) in cosmetic surgery. Plastic and reconstructive surgery. 2001;107(1):229-37; discussion 38-9.
  9. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 1998;85(6):638-46.
  10. Pallua N, Wolter T, Markowicz M. Platelet-rich plasma in burns. Burns. 2010;36(1):4-8.
  11. Lacci KM, Dardik A. Platelet-rich plasma: support for its use in wound healing. The Yale journal of biology and medicine. 2010;83(1):1.
  12. Carter MJ, Fylling CP, Parnell LK. Use of platelet rich plasma gel on wound healing: a systematic review and meta-analysis. Eplasty. 2011;11.
  13. Yol S, Tekin A, Yilmaz H, Küçükkartallar T, Esen H, Çaǧlayan O, et al. Effects of platelet rich plasma on colonic anastomosis. Journal of Surgical Research. 2008;146(2):190-4.
  14. Almdahl SM, Veel T, Halvorsen P, Vold MB, Mølstad P. Randomized prospective trial of saphenous vein harvest site infection after wound closure with and without topical application of autologous platelet-rich plasma. European Journal of Cardio-Thoracic Surgery. 2011;39(1):44-8.
  15. Everts PAM, Devilee R, Brown Mahoney C, Eeftinck‐Schattenkerk M, Box H, Knape J, et al. Platelet gel and fibrin sealant reduce allogeneic blood transfusions in total knee arthroplasty. Acta Anaesthesiologica Scandinavica. 2006;50(5):593-9.
  16. Hom DB, Linzie BM, Huang TC. The healing effects of autologous platelet gel on acute human skin wounds. Archives of facial plastic surgery. 2007;9(3):174-83.
  17. Fresno L, Fondevila D, Bambo O, Chacaltana A, Garcia F, Andaluz A. Effects of platelet-rich plasma on intestinal wound healing in pigs. The Veterinary Journal. 2010;185(3):322-7.
  18. Ma L, Elliott SN, Cirino G, Buret A, Ignarro LJ, Wallace JL. Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release. Proceedings of the National Academy of Sciences. 2001;98(11):6470-5.
  19. Wasterlain AS, Braun HJ, Dragoo JL. Contents and formulations of platelet-rich plasma. Operative Techniques in Orthopaedics. 2012;22(1):33-42.
  20. Kurita J, Miyamoto M, Ishii Y, Aoyama J, Takagi G, Naito Z, et al. Enhanced vascularization by controlled release of platelet-rich plasma impregnated in biodegradable gelatin hydrogel. The Annals of thoracic surgery. 2011;92(3):837-44.
  21. Lee H-R, Park KM, Joung YK, Park KD, Do SH. Platelet-rich plasma loaded hydrogel scaffold enhances chondrogenic differentiation and maturation with up-regulation of CB1 and CB2. Journal of Controlled Release. 2012;159(3):332-7.
  22. Nagae M, Ikeda T, Mikami Y, Hase H, Ozawa H, Matsuda K-I, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue engineering. 2007;13(1):147-58.
  23. Ohba S, Wang W, Itoh S, Takagi Y, Nagai A, Yamashita K. Efficacy of platelet‐rich plasma gel and hyaluronan hydrogel as carriers of electrically polarized hydroxyapatite microgranules for accelerating bone formation. Journal of Biomedical Materials Research Part A. 2012;100(11):3167-76.
  24. Lu HH, Vo JM, Chin HS, Lin J, Cozin M, Tsay R, et al. Controlled delivery of platelet‐rich plasma‐derived growth factors for bone formation. Journal of Biomedical Materials Research Part A. 2008;86(4):1128-36.
  25. Rossi S, Faccendini A, Bonferoni M, Ferrari F, Sandri G, Del Fante C, et al. “Sponge-like” dressings based on biopolymers for the delivery of platelet lysate to skin chronic wounds. International journal of pharmaceutics. 2013;440(2):207-15.
  26. Sandri G, Bonferoni MC, Rossi S, Ferrari F, Mori M, Del Fante C, et al. Thermosensitive eyedrops containing platelet lysate for the treatment of corneal ulcers. International journal of pharmaceutics. 2012;426(1):1-6.
  27. Sandri G, Bonferoni MC, Rossi S, Ferrari F, Mori M, Del Fante C, et al. Platelet lysate formulations based on mucoadhesive polymers for the treatment of corneal lesions. Journal of Pharmacy and Pharmacology. 2011;63(2):189-98.
  28. Anitua E, Sanchez M, Orive G, Andia I. The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials. 2007;28(31):4551-60.
  29. Kamerzell TJ, Esfandiary R, Joshi SB, Middaugh CR, Volkin DB. Protein–excipient interactions: Mechanisms and biophysical characterization applied to protein formulation development. Advanced drug delivery reviews. 2011;63(13):1118-59.
  30. Wang W. Instability, stabilization, and formulation of liquid protein pharmaceuticals. International journal of pharmaceutics. 1999;185(2):129-88.
  31. Peppas N, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. European journal of pharmaceutics and biopharmaceutics. 2000;50(1):27-46.
  32. Khamanga S, Walker RB. Drug transport mechanisms from carbopol/Eudragit verapamil sustained-release tablets. Dissol Technol. 2011;1:30-8.
  33. Barry B, Meyer M. The rheological properties of carbopol gels I. Continuous shear and creep properties of carbopol gels. International journal of pharmaceutics. 1979;2(1):1-25.
  34. Schiffter H. The delivery of drugs–peptides and proteins: Pergamon Press (Elsevier), Oxford, UK; 2011. 587-604 p.
  35. Hovgaard L, Frokjaer S, van de Weert M. Pharmaceutical formulation development of peptides and proteins: CRC Press; 2012.
  36. Tsai P, Volkin DB, Dabora JM, Thompson KC, Bruner MW, Gress JO, et al. Formulation design of acidic fibroblast growth factor. Pharmaceutical research. 1993;10(5):649-59.
  37. Sinko PJ. Martin's Physical Pharmacy and Pharmaceutical Sciences. 5th ed. Philadelphia: Lipincott Williams & Wilkins; 2006.
  38. Kurganov B, Rafikova E, Dobrov E. Kinetics of thermal aggregation of tobacco mosaic virus coat protein. Biochemistry (Moscow). 2002;67(5):525-33.
  39. Zhang J, Peng X, Jonas A, Jonas J. NMR study of the cold, heat, and pressure unfolding of ribonuclease A. Biochemistry. 1995;34(27):8631-41.
  40. Liu Y, Sturtevant JM. The observed change in heat capacity accompanying the thermal unfolding of proteins depends on the composition of the solution and on the method employed to change the temperature of unfolding. Biochemistry. 1996;35(9):3059-62.