Use of injectable platelet rich fibrin (IPRF) as LDD vehicle containing doxycycline in periodontal Therapy – In vitro study
Main Article Content
Keywords
Platelet-Rich Fibrin; Drug Delivery Systems
Abstract
Local drug delivery systems (LLD) are preferred over systemic antibiotic therapy in indicated cases to avoid unnecessary large doses of drug, development of antibiotic resistance etc. The search for the more suitable novel vehicle for the local drug delivery that can render controlled release of drug at periodontally infected sites are widely researched. i-PRF being autologous and injectable could be a suitable vehicle for local delivery of drugs. This study aims to evaluate the possibility of using i-PRF as a controlled release drug vehicle in periodontal therapy.
Methods: i-PRF obtained from centrifugation of 10 ml of blood collected from volunteers are mixed with known concentration of doxycycline drug and allowed to become a gel. The drug loaded gel is dispensed in artificial saliva and allowed to degrade. At specific time intervals (1 hr, 3 hr, 5 hr, 7 hr, 3d, 5d, 7d, 9d, 14d) aliquot of the 200 microliter were collected from each sample and subjected for spectrophotometric analysis.
Results: The spectrophotometric results show that the drug was detected in all the samples obtained from the 1 hr to the 14th day. Final concentration in the eluted samples seem to be gradually reducing from the 1 hr to the 7 th hour and a steep downward pattern in the concentration was absorbed from the 3 rd day until 14th day.
Conclusions: The controlled drug release profile of the i-PRF shows its a potential and suitable vehicle for LDD system in periodontal therapy. Additionally, properties like the syringeability, in-situ gel formation, and autologous fibrin nature may facilitate its direct delivery into the periodontal pocket, getting moulded to the pocket shape with attachment to the soft and hard tissue thereby ensuring the retention of the drug loaded i-PRF in the confined pocket environment.
References
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Dentistry Journal. 2019. p. 108. doi:10.3390/dj7040108
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22. Kumar JK, Surendranath P, Eswaramoorthy R. Regeneration of immature incisor using platelet rich fibrin: report of a novel clinical application. BMC Oral Health. 2023;23: 69.
23. Bai M-Y, Wang C-W, Wang J-Y, Lin M-F, Chan WP. Three-dimensional structure and cytokine distribution of platelet-rich fibrin. Clinics . 2017;72: 116–124.
24. Kobayashi E, Flückiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B, et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig. 2016;20: 2353–2360.
25. Nagaraja S, Mathew S, Abraham A, Ramesh P, Chandanala S. Evaluation of vascular endothelial growth factor - A release from platelet-rich fibrin, platelet-rich fibrin matrix, and dental pulp at different time intervals. J Conserv Dent. 2020;23: 359–363.
26. Varela HA, Souza JCM, Nascimento RM, Araújo RF Jr, Vasconcelos RC, Cavalcante RS, et al. Injectable platelet rich fibrin: cell content, morphological, and protein characterization. Clin Oral Investig. 2019;23: 1309–1318.
27. Faour NH, Dayoub S, Hajeer MY. Evaluation of the Hyaluronic Acid Versus the Injectable Platelet-Rich Fibrin in the Management of the Thin Gingival Phenotype: A Split-Mouth Randomized Controlled Clinical Trial. Cureus. 2022. doi:10.7759/cureus.25104
28. Elbarbary A, Reda A, ELaziz AA. Evaluation of the Addition of Injectable Platelet Rich Fibrin to Xenograft in Management of Periodontal Intraosseous Defects. “Randomized Controlled Trial.” Al-Azhar Dental Journal for Girls. 2022. pp. 321–330. doi:10.21608/adjg.2022.111166.1461
29. Rajeshkumar S, Parameswari RP, Sandhiya D, Al-Ghanim KA, Nicoletti M, Govindarajan M. Green Synthesis, Characterization and Bioactivity of Seed-Wrapped Zinc Oxide Nanoparticles. Molecules. 2023;28. doi:10.3390/molecules28062818
30. Rajeshkumar S, Santhoshkumar J, Parameswari RP, Saravanan S, Balusamy SR, Arunachalam K. Degradation of Toxic Dye and Antimicrobial and Free Radical Potential of Environmental Benign Zinc Oxide Nanoparticles. Bioinorg Chem Appl. 2022;2022: 4513208.
31. Rajeshkumar S, Parameswari RP, Jayapriya J, Tharani M, Ali H, Aljarba NH, et al. Apoptotic and Antioxidant Activity of Gold Nanoparticles Synthesized Using Marine Brown Seaweed: An In Vitro Study. Biomed Res Int. 2022;2022: 5746761.
32. Rajeshkumar S, Vanaja M, Kalirajan A. Degradation of Toxic Dye Using Phytomediated Copper Nanoparticles and Its Free-Radical Scavenging Potential and Antimicrobial Activity against Environmental Pathogens. Bioinorg Chem Appl. 2021;2021: 1222908.
33. Devi NS, Ganapathy DM, Rajeshkumar S, Maiti S. Characterization and antimicrobial activity of cerium oxide nanoparticles synthesized using neem and ginger. J Adv Pharm Technol Res. 2022;13: S491–S495.
34. Motamedi S. Comparative Effectiveness of Subgingival Irrigation and Systemic Administration of Doxycycline Periodontal Therapy. 1993.
35. Cosgarea R, Ramseier CA, Jepsen S, Arweiler NB, Jervøe-Storm PM, Batori-Andronescu I, et al. One-Year Clinical, Microbiological and Immunological Results of Local Doxycycline orAntimicrobial Photodynamic Therapy for Recurrent/Persisting Periodontal Pockets: A Randomized Clinical Trial. Antibiotics (Basel). 2022;11. doi:10.3390/antibiotics11060738
36. Sufaru I-G, Teslaru S, Pasarin L, Iovan G, Stoleriu S, Solomon SM. Host Response Modulation Therapy in the Diabetes Mellitus-Periodontitis Conjuncture: A Narrative Review. Pharmaceutics. 2022;14. doi:10.3390/pharmaceutics14081728
37. Mittal P, Gokhale ST, Manjunath S, Al-Qahtani SM, Magbol MA, Nagate RR, et al. Comparative Evaluation of Locally Administered 2% Gel Fabricated from Lemongrass Polymer and 10% Doxycycline Hyclate Gel as an Adjunct to Scaling and Root Planing in the Treatment of Chronic Periodontitis-A Randomized Controlled Trial. Polymers . 2022;14. doi:10.3390/polym14142766
38. Crisci A. New Platelet Concentrates Useful in Tissue Repair. Platelet-rich Fibrin with Leukocytes (L-PRF), Advanced Platelet-Rich Fibrin (A-PRF) and Injectable Platelet-rich Fibrin (i-PRF). 2021. doi:10.9734/bpi/mono/978-93-91473-15-0
39. Miron RJ, Choukroun J. Platelet Rich Fibrin in Regenerative Dentistry: Biological Background and Clinical Indications. John Wiley & Sons; 2017.
40. Gorog S. Ultraviolet-Visible Spectrophotometry in Pharmaceutical Analysis. CRC Press; 2018.
41. Nasra MMA, Khiri HM, Hazzah HA, Abdallah OY. Formulation, in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of periodontitis. Drug Delivery. 2017. pp. 133–142. doi:10.1080/10717544.2016.1233591
42. Aggarwal G, Verma S, Gupta M, Nagpal M. Local Drug Delivery Based Treatment Approaches for Effective Management of Periodontitis. Current Drug Therapy. 2019. pp. 135–152. doi:10.2174/1574885514666190103112855
43. Dabhi MR, Nagori SA, Gohel MC, Parikh RK, Sheth NR. Formulation development of smart gel
periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design. Drug Deliv. 2010;17: 520–531.
44. Ghitman J, Biru EI, Stan R, Iovu H. Review of hybrid PLGA nanoparticles: Future of smart drug delivery and theranostics medicine. Materials & Design. 2020. p. 108805. doi:10.1016/j.matdes.2020.108805
45. Duch MC, Budinger GRS, Liang YT, Soberanes S, Urich D, Chiarella SE, et al. Minimizing oxidation and stable nanoscale dispersion improves the biocompatibility of graphene in the lung. Nano Lett. 2011;11: 5201–5207.
46. Zhao H, Hu J, Zhao L. The effect of drug dose and duration of adjuvant Amoxicillin-plus-Metronidazole to full-mouth scaling and root planing in periodontitis: a systematic review and meta-analysis. Clin Oral Investig. 2021;25: 5671–5685.
47. McGowan K, McGowan T, Ivanovski S. Optimal dose and duration of amoxicillin-plus-metronidazole as an adjunct to non-surgical periodontal therapy: A systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Periodontol. 2018;45: 56–67.
48. Agossa K, Delepierre A, Lizambard M, Delcourt-Debruyne E, Siepmann J, Siepmann F, et al. In-situ forming implants for dual controlled release of chlorhexidine and ibuprofen for periodontitis treatment: Microbiological and mechanical key properties. Journal of Drug Delivery Science and Technology. 2020. p. 101956. doi:10.1016/j.jddst.2020.101956
49. Rafiee A, Memarpour M, Taghvamanesh S, Karami F, Karami S, Morowvat MH. Drug Delivery Assessment of a Novel Triple Antibiotic-Eluting Injectable Platelet-Rich Fibrin Scaffold: An In Vitro Study. Curr Pharm Biotechnol. 2021;22: 380–388.
50. Gagandeep, Gagandeep, Singh RJ, Thind BK. Injectable platelet-rich fibrin (albumin gel and liquid platelet-rich fibrin). International journal of health sciences. 2021. pp. 269–273. doi:10.53730/ijhs.v5ns2.5770
2. Nunn ME. Understanding the etiology of periodontitis: an overview of periodontal risk factors. Periodontology 2000. 2003. pp. 11–23. doi:10.1046/j.0906-6713.2002.03202.x
3. Bathla S. Scaling and Root Planing. Textbook of Periodontics. 2017. pp. 434–434. doi:10.5005/jp/books/13037_45
4. Lõivukene K, Pähkla E-R, Koppel T, Saag M, Naaber P. The microbiological status of patients with periodontitis in southern Estonia after non-surgical periodontal therapy. Stomatologija. 2005;7: 45–47.
5. Pal A, Paul S, Perry R, Puryer J. Is the Use of Antimicrobial Photodynamic Therapy or Systemic Antibiotics More Effective in Improving Periodontal Health When Used in Conjunction with Localised Non-Surgical Periodontal Therapy? A Systematic Review.
Dentistry Journal. 2019. p. 108. doi:10.3390/dj7040108
6. Keestra JAJ, Grosjean I, Coucke W, Quirynen M, Teughels W. Non-surgical periodontal therapy with systemic antibiotics in patients with untreated chronic periodontitis: a systematic review and meta-analysis. Journal of Periodontal Research. 2015. pp. 294–314. doi:10.1111/jre.12221
7. American Academy of Periodontology Statement on Local Delivery of Sustained or Controlled Release Antimicrobials as Adjunctive Therapy in the Treatment of Periodontitis. J Periodontol. 2006;77: 1458.
8. Ramanauskaite E, Machiulskiene V. Antiseptics as adjuncts to scaling and root planing in the treatment of periodontitis: a systematic literature review. BMC Oral Health. 2020;20: 143.
9. Teughels W, Feres M, Oud V, Martín C, Matesanz P, Herrera D. Adjunctive effect of systemic antimicrobials in periodontitis therapy: A systematic review and meta‐analysis. Journal of Clinical Periodontology. 2020. pp. 257–281. doi:10.1111/jcpe.13264
10. Nandan B, Barman Roy D, Pant VA, Gupta V, Bhaduria U, Kaur H, et al. Comparative Evaluation of Cost-Effectiveness, Clinical and Microbiological Parameters of Systemic Antibiotics Versus Local Drug Delivery in Aggressive Periodontitis. Cureus. 2022;14: e20985.
11. Quirynen M, Teughels W, Van Steenberghe D. Microbial shifts after subgingival debridement and formation of bacterial resistance when combined with local or systemic antimicrobials. Oral Diseases. 2003. pp. 30–37. doi:10.1034/j.1601-0825.9.s1.6.x
12. Costa JV, Portugal J, Neves CB, Bettencourt AF. Should local drug delivery systems be used in dentistry? Drug Deliv Transl Res. 2022;12: 1395–1407.
13. Zhang Y, Jiang R, Lei L, Yang Y, Hu T. Drug delivery systems for oral disease applications. J Appl Oral Sci. 2022;30: e20210349.
14. Batool F, Agossa K, Lizambard M, Petit C, Bugueno IM, Delcourt-Debruyne E, et al. In-situ forming implants loaded with chlorhexidine and ibuprofen for periodontal treatment: Proof of concept study in vivo. Int J Pharm. 2019;569: 118564.
15. Cao F, Gui S-Y, Gao X, Zhang W, Fu Z-Y, Tao L-M, et al. Research progress of natural product-based nanomaterials for the treatment of inflammation-related diseases. Materials &Design. 2022. p. 110686. doi:10.1016/j.matdes.2022.110686
16. Miron RJ, Choukroun J. Future Research with Platelet Rich Fibrin. Platelet Rich Fibrin in Regenerative Dentistry: Biological Background and Clinical Indications. 2017. pp. 251–261. doi:10.1002/9781119406792.ch15
17. Choukroun J, Simonpieri A, Girard M-O, Fioretti F, Dohan S, Dohan D. Platelet Rich Fibrin (PRF) : un nouveau biomatériau de cicatrisation. Implantodontie. 2004. pp. 229–235. doi:10.1016/j.implan.2004.07.002
18. Thamaraiselvan M, Elavarasu S, Thangakumaran S, Gadagi JS, Arthie T. Comparative clinical evaluation of coronally advanced flap with or without platelet rich fibrin membrane in the treatment of isolated gingival recession. J Indian Soc Periodontol. 2015;19: 66–71.
19. Panda S, Satpathy A, Das AC, Kumar M, Mishra L, Gupta S, et al. Additive Effect of Platelet Rich Fibrin with Coronally Advanced Flap Procedure in Root Coverage of Miller’s Class I and II Recession Defects—A PRISMA Compliant Systematic Review and Meta-Analysis. Materials. 2020. p. 4314. doi:10.3390/ma13194314
20. Panda S, Jayakumar ND, Sankari M, Varghese SS, Kumar DS. Platelet rich fibrin and xenograft in treatment of intrabony defect. Contemp Clin Dent. 2014;5: 550–554.
21. Panda S, Sankari M, Satpathy A, Jayakumar D, Mozzati M, Mortellaro C, et al. Adjunctive Effect of Autologus Platelet-Rich Fibrin to Barrier Membrane in the Treatment of Periodontal Intrabony Defects. J Craniofac Surg. 2016;27: 691–696.
22. Kumar JK, Surendranath P, Eswaramoorthy R. Regeneration of immature incisor using platelet rich fibrin: report of a novel clinical application. BMC Oral Health. 2023;23: 69.
23. Bai M-Y, Wang C-W, Wang J-Y, Lin M-F, Chan WP. Three-dimensional structure and cytokine distribution of platelet-rich fibrin. Clinics . 2017;72: 116–124.
24. Kobayashi E, Flückiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B, et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig. 2016;20: 2353–2360.
25. Nagaraja S, Mathew S, Abraham A, Ramesh P, Chandanala S. Evaluation of vascular endothelial growth factor - A release from platelet-rich fibrin, platelet-rich fibrin matrix, and dental pulp at different time intervals. J Conserv Dent. 2020;23: 359–363.
26. Varela HA, Souza JCM, Nascimento RM, Araújo RF Jr, Vasconcelos RC, Cavalcante RS, et al. Injectable platelet rich fibrin: cell content, morphological, and protein characterization. Clin Oral Investig. 2019;23: 1309–1318.
27. Faour NH, Dayoub S, Hajeer MY. Evaluation of the Hyaluronic Acid Versus the Injectable Platelet-Rich Fibrin in the Management of the Thin Gingival Phenotype: A Split-Mouth Randomized Controlled Clinical Trial. Cureus. 2022. doi:10.7759/cureus.25104
28. Elbarbary A, Reda A, ELaziz AA. Evaluation of the Addition of Injectable Platelet Rich Fibrin to Xenograft in Management of Periodontal Intraosseous Defects. “Randomized Controlled Trial.” Al-Azhar Dental Journal for Girls. 2022. pp. 321–330. doi:10.21608/adjg.2022.111166.1461
29. Rajeshkumar S, Parameswari RP, Sandhiya D, Al-Ghanim KA, Nicoletti M, Govindarajan M. Green Synthesis, Characterization and Bioactivity of Seed-Wrapped Zinc Oxide Nanoparticles. Molecules. 2023;28. doi:10.3390/molecules28062818
30. Rajeshkumar S, Santhoshkumar J, Parameswari RP, Saravanan S, Balusamy SR, Arunachalam K. Degradation of Toxic Dye and Antimicrobial and Free Radical Potential of Environmental Benign Zinc Oxide Nanoparticles. Bioinorg Chem Appl. 2022;2022: 4513208.
31. Rajeshkumar S, Parameswari RP, Jayapriya J, Tharani M, Ali H, Aljarba NH, et al. Apoptotic and Antioxidant Activity of Gold Nanoparticles Synthesized Using Marine Brown Seaweed: An In Vitro Study. Biomed Res Int. 2022;2022: 5746761.
32. Rajeshkumar S, Vanaja M, Kalirajan A. Degradation of Toxic Dye Using Phytomediated Copper Nanoparticles and Its Free-Radical Scavenging Potential and Antimicrobial Activity against Environmental Pathogens. Bioinorg Chem Appl. 2021;2021: 1222908.
33. Devi NS, Ganapathy DM, Rajeshkumar S, Maiti S. Characterization and antimicrobial activity of cerium oxide nanoparticles synthesized using neem and ginger. J Adv Pharm Technol Res. 2022;13: S491–S495.
34. Motamedi S. Comparative Effectiveness of Subgingival Irrigation and Systemic Administration of Doxycycline Periodontal Therapy. 1993.
35. Cosgarea R, Ramseier CA, Jepsen S, Arweiler NB, Jervøe-Storm PM, Batori-Andronescu I, et al. One-Year Clinical, Microbiological and Immunological Results of Local Doxycycline orAntimicrobial Photodynamic Therapy for Recurrent/Persisting Periodontal Pockets: A Randomized Clinical Trial. Antibiotics (Basel). 2022;11. doi:10.3390/antibiotics11060738
36. Sufaru I-G, Teslaru S, Pasarin L, Iovan G, Stoleriu S, Solomon SM. Host Response Modulation Therapy in the Diabetes Mellitus-Periodontitis Conjuncture: A Narrative Review. Pharmaceutics. 2022;14. doi:10.3390/pharmaceutics14081728
37. Mittal P, Gokhale ST, Manjunath S, Al-Qahtani SM, Magbol MA, Nagate RR, et al. Comparative Evaluation of Locally Administered 2% Gel Fabricated from Lemongrass Polymer and 10% Doxycycline Hyclate Gel as an Adjunct to Scaling and Root Planing in the Treatment of Chronic Periodontitis-A Randomized Controlled Trial. Polymers . 2022;14. doi:10.3390/polym14142766
38. Crisci A. New Platelet Concentrates Useful in Tissue Repair. Platelet-rich Fibrin with Leukocytes (L-PRF), Advanced Platelet-Rich Fibrin (A-PRF) and Injectable Platelet-rich Fibrin (i-PRF). 2021. doi:10.9734/bpi/mono/978-93-91473-15-0
39. Miron RJ, Choukroun J. Platelet Rich Fibrin in Regenerative Dentistry: Biological Background and Clinical Indications. John Wiley & Sons; 2017.
40. Gorog S. Ultraviolet-Visible Spectrophotometry in Pharmaceutical Analysis. CRC Press; 2018.
41. Nasra MMA, Khiri HM, Hazzah HA, Abdallah OY. Formulation, in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of periodontitis. Drug Delivery. 2017. pp. 133–142. doi:10.1080/10717544.2016.1233591
42. Aggarwal G, Verma S, Gupta M, Nagpal M. Local Drug Delivery Based Treatment Approaches for Effective Management of Periodontitis. Current Drug Therapy. 2019. pp. 135–152. doi:10.2174/1574885514666190103112855
43. Dabhi MR, Nagori SA, Gohel MC, Parikh RK, Sheth NR. Formulation development of smart gel
periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design. Drug Deliv. 2010;17: 520–531.
44. Ghitman J, Biru EI, Stan R, Iovu H. Review of hybrid PLGA nanoparticles: Future of smart drug delivery and theranostics medicine. Materials & Design. 2020. p. 108805. doi:10.1016/j.matdes.2020.108805
45. Duch MC, Budinger GRS, Liang YT, Soberanes S, Urich D, Chiarella SE, et al. Minimizing oxidation and stable nanoscale dispersion improves the biocompatibility of graphene in the lung. Nano Lett. 2011;11: 5201–5207.
46. Zhao H, Hu J, Zhao L. The effect of drug dose and duration of adjuvant Amoxicillin-plus-Metronidazole to full-mouth scaling and root planing in periodontitis: a systematic review and meta-analysis. Clin Oral Investig. 2021;25: 5671–5685.
47. McGowan K, McGowan T, Ivanovski S. Optimal dose and duration of amoxicillin-plus-metronidazole as an adjunct to non-surgical periodontal therapy: A systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Periodontol. 2018;45: 56–67.
48. Agossa K, Delepierre A, Lizambard M, Delcourt-Debruyne E, Siepmann J, Siepmann F, et al. In-situ forming implants for dual controlled release of chlorhexidine and ibuprofen for periodontitis treatment: Microbiological and mechanical key properties. Journal of Drug Delivery Science and Technology. 2020. p. 101956. doi:10.1016/j.jddst.2020.101956
49. Rafiee A, Memarpour M, Taghvamanesh S, Karami F, Karami S, Morowvat MH. Drug Delivery Assessment of a Novel Triple Antibiotic-Eluting Injectable Platelet-Rich Fibrin Scaffold: An In Vitro Study. Curr Pharm Biotechnol. 2021;22: 380–388.
50. Gagandeep, Gagandeep, Singh RJ, Thind BK. Injectable platelet-rich fibrin (albumin gel and liquid platelet-rich fibrin). International journal of health sciences. 2021. pp. 269–273. doi:10.53730/ijhs.v5ns2.5770
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Jun 1, 2023
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Ashwin Jaikumar Ram, Thamaraiselvan Murugan, Jayakumar ND, & Dhanraj Ganapathy. (2023). Use of injectable platelet rich fibrin (IPRF) as LDD vehicle containing doxycycline in periodontal Therapy – In vitro study. Journal of Population Therapeutics and Clinical Pharmacology, 30(12), 201–209. https://doi.org/10.47750/jptcp.2023.30.12.023
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