Preparation and Administration of a Controlled-Release Delivery System of Chitosan Hydrogel loaded with Methadone and Piroxicam in Experimental Defect of Tibial in Rats; Histopathological Evaluation
-
Pegah Khosravian
,
Moosa Javdani
,
Melika Masoudi
,
Abdolnaser Mohebi
,
Amin Bigham Sadegh
,
Abolfazl Barzegar
Abstract
Purpose: In this study, a controlled release drug delivery system loaded with piroxicam and methadone was synthesized and used subcutaneously in rat with experimental tibial defect and healing were assessed histopathologically.
Materials and Methods: For this purpose 100 adult female rats were were randomly divided into five equal groups; group control, chitosan group, piroxicam group, methadone group, and piroxicam-methadone group. The morphological structure of the synthesized drug systems was studied by scanning electron microscope. In addition, the structure of the hydrogels was investigated by fourier transform infrared spectroscopy and while releasing the hydrogels gelation time, the release of piroxicam and methadone from the hydrogels were evaluated in vitro.
Results: Histological results of the 3rd day of the study showed the lowest extent and severity of inflammation in the chitosan, piroxicam, and piroxicam-methadone groups, while on the 7th day, tissue inflammation and the extent of bleeding was lower in the piroxicam, methadone, and piroxicam-methadone groups than in the other groups. Evaluation of new bone formation on day 21 showed that the chitosan, piroxicam, and methadone groups had better repair than the other groups.
Conclusion: It seems that in the control group that did not receive any treatment intervention, following the experimental bone defect, the highest inflammatory response was observed in histological examination and finally the weakest bone repair. On the other hand, the presence of piroxicam, methadone and chitosan in the piroxicam-methadone group (all of which have anti-inflammatory effects) also seems to have a negative effect on repair.
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10- Marcelino Montiel-Herrera et al., "N-(furfural) chitosan hydrogels based on Diels–Alder cycloadditions and application as microspheres for controlled drug release." Carbohydrate polymers, Vol. 128pp. 220-27, (2015).
11- Abolfazl Barzegar and Moosa Javdani, "Application of chitosan hydrogels in traumatic spinal cord injury; a therapeutic approach based on the anti-inflammatory and antioxidant properties of selenium nanoparticles." Frontiers in Biomedical Technologies, (2022).
12- Marcelino Montiel-Herrera et al., "N-(furfural) chitosan hydrogels based on Diels–Alder cycloadditions and application as microspheres for controlled drug release." Carbohydrate polymers, Vol. 128pp. 220-27, (2015).
13- Oluwadamilola M Kolawole, Wing Man Lau, and Vitaliy V Khutoryanskiy, "Chitosan/β-glycerophosphate in situ gelling mucoadhesive systems for intravesical delivery of mitomycin-C." International Journal of Pharmaceutics: X, Vol. 1p. 100007, (2019).
14- Moosa Javdani, Farid Shahbandari, Ehsan Soleymanijadian, Mohammad Hashemnia, and Abolfazl Barzegar, "Induction of Experimental Endometriosis in Rat: Evaluation of Systemic Inflammatory Response and Liver Tissue Changes." Tabari Biomedical Student Research Journal, Vol. 4 (No. 4), pp. 1-12, (2022).
15- Moosa Javdani, Maryam Nafar, Abdolnaser Mohebi, Pegah Khosravian, and Abolfazl Barzegar, "Evaluation of Leukocyte Response due to Implant of a Controlled Released Drug Delivery System of Chitosan Hydrogel Loaded with Selenium Nanoparticle in Rats with Experimental Spinal Cord Injury." Tabari Biomedical Student Research Journal, Vol. 4 (No. 2), pp. 1-16, (2022).
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19- Jukka Pajarinen et al., "Mesenchymal stem cell-macrophage crosstalk and bone healing." Biomaterials, Vol. 196pp. 80-89, (2019).
20- Bilal Osta, Giulia Benedetti, and Pierre Miossec, "Classical and paradoxical effects of TNF-α on bone homeostasis." Frontiers in immunology, Vol. 5p. 48, (2014).
21- Sheeny K Lan Levengood and Miqin Zhang, "Chitosan-based scaffolds for bone tissue engineering." Journal of Materials Chemistry B, Vol. 2 (No. 21), pp. 3161-84, (2014).
22- Jayachandran Venkatesan and Se-Kwon Kim, "Chitosan composites for bone tissue engineering—an overview." Marine drugs, Vol. 8 (No. 8), pp. 2252-66, (2010).
23- Yang-Jo Seol et al., "Chitosan sponges as tissue engineering scaffolds for bone formation." Biotechnology letters, Vol. 26 (No. 13), pp. 1037-41, (2004).
24- RAA Muzzarelli et al., "Stimulatory effect on bone formation exerted by a modified chitosan." Biomaterials, Vol. 15 (No. 13), pp. 1075-81, (1994).
25- Piet Geusens, Pieter J Emans, Joost JA de Jong, and Joop van den Bergh, "NSAIDs and fracture healing." Current opinion in rheumatology, Vol. 25 (No. 4), pp. 524-31, (2013).
26- Alexander Beck, Khaled Salem, Gert Krischak, Lothar Kinzl, Mark Bischoff, and Andreas Schmelz, "Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics effects on bone healing." Operative Orthopadie und Traumatologie, Vol. 17 (No. 6), pp. 569-78, (2005).
27- Christopher J Richards, Kenneth W Graf, and Rakesh P Mashru, "The effect of opioids, alcohol, and nonsteroidal anti-inflammatory drugs on fracture union." Orthopedic Clinics, Vol. 48 (No. 4), pp. 433-43, (2017).
28- Robert W van Esch, Maurice M Kool, and Saskia van As, "NSAIDs can have adverse effects on bone healing." Medical hypotheses, Vol. 81 (No. 2), pp. 343-46, (2013).
29- J David Clark et al., "Morphine reduces local cytokine expression and neutrophil infiltration after incision." Molecular pain, Vol. 3pp. 1744-8069-3-28, (2007).
30- Yong-min Liu, Sheng-mei Zhu, Kui-rong Wang, Zhi-ying Feng, and Qing-lian Chen, "Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain." Journal of Zhejiang University SCIENCE B, Vol. 9 (No. 11), pp. 895-902, (2008).
31- Flaminia Coluzzi, Maria Sole Scerpa, and Marco Centanni, "The effect of opiates on bone formation and bone healing." Current Osteoporosis Reports, Vol. 18 (No. 3), pp. 325-35, (2020).
32- Alexander Beck, Khaled Salem, Gert Krischak, Lothar Kinzl, Mark Bischoff, and Andreas Schmelz, "Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics effects on bone healing." Operative Orthopadie und Traumatologie, Vol. 17 (No. 6), pp. 569-78, (2005).
33- Larissa B Cardozo et al., "Evaluation of the effects of methadone and tramadol on postoperative analgesia and serum interleukin-6 in dogs undergoing orthopaedic surgery." BMC veterinary research, Vol. 10 (No. 1), pp. 1-7, (2014).
2- Tamiyo Kon et al., "Expression of osteoprotegerin, receptor activator of NF‐κB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing." Journal of Bone and Mineral Research, Vol. 16 (No. 6), pp. 1004-14, (2001).
3- Florence Loi, Luis A Córdova, Jukka Pajarinen, Tzu-hua Lin, Zhenyu Yao, and Stuart B Goodman, "Inflammation, fracture and bone repair." Bone, Vol. 86pp. 119-30, (2016).
4- YM Kuang, YC Zhu, Ying Kuang, Yuan Sun, Chen Hua, and WY He, "Changes of the immune cells, cytokines and growth hormone in teenager drug addicts." Xi bao yu fen zi Mian yi xue za zhi= Chinese Journal of Cellular and Molecular Immunology, Vol. 23 (No. 9), pp. 821-23, (2007).
5- Alexander Beck, Khaled Salem, Gert Krischak, Lothar Kinzl, Mark Bischoff, and Andreas Schmelz, "Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics effects on bone healing." Operative Orthopadie und Traumatologie, Vol. 17 (No. 6), pp. 569-78, (2005).
6- Anneluuk LC Lindenhovious, Gijs TT Helmerhorts, Alexandra C Schnellen, Mark Vrahas, David Ring, and Peter Kloen, "Differences in prescription of narcotic pain medication after operative treatment of hip and ankle fractures in the United States and The Netherlands." Journal of Trauma and Acute Care Surgery, Vol. 67 (No. 1), pp. 160-64, (2009).
7- Javad Parvizi and Michael R Bloomfield, "Multimodal pain management in orthopedics: implications for joint arthroplasty surgery." Orthopedics, Vol. 36 (No. 2), pp. 7-14, (2013).
8- Ippokratis Pountos, Theodora Georgouli, Giorgio M Calori, and Peter V Giannoudis, "Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis." The Scientific World Journal, Vol. 2012(2012).
9- Xiangjun Kong, Jing Wang, Lingyan Cao, Yuanman Yu, and Changsheng Liu, "Enhanced osteogenesis of bone morphology protein-2 in 2-N, 6-O-sulfated chitosan immobilized PLGA scaffolds." Colloids and Surfaces B: Biointerfaces, Vol. 122pp. 359-67, (2014).
10- Marcelino Montiel-Herrera et al., "N-(furfural) chitosan hydrogels based on Diels–Alder cycloadditions and application as microspheres for controlled drug release." Carbohydrate polymers, Vol. 128pp. 220-27, (2015).
11- Abolfazl Barzegar and Moosa Javdani, "Application of chitosan hydrogels in traumatic spinal cord injury; a therapeutic approach based on the anti-inflammatory and antioxidant properties of selenium nanoparticles." Frontiers in Biomedical Technologies, (2022).
12- Marcelino Montiel-Herrera et al., "N-(furfural) chitosan hydrogels based on Diels–Alder cycloadditions and application as microspheres for controlled drug release." Carbohydrate polymers, Vol. 128pp. 220-27, (2015).
13- Oluwadamilola M Kolawole, Wing Man Lau, and Vitaliy V Khutoryanskiy, "Chitosan/β-glycerophosphate in situ gelling mucoadhesive systems for intravesical delivery of mitomycin-C." International Journal of Pharmaceutics: X, Vol. 1p. 100007, (2019).
14- Moosa Javdani, Farid Shahbandari, Ehsan Soleymanijadian, Mohammad Hashemnia, and Abolfazl Barzegar, "Induction of Experimental Endometriosis in Rat: Evaluation of Systemic Inflammatory Response and Liver Tissue Changes." Tabari Biomedical Student Research Journal, Vol. 4 (No. 4), pp. 1-12, (2022).
15- Moosa Javdani, Maryam Nafar, Abdolnaser Mohebi, Pegah Khosravian, and Abolfazl Barzegar, "Evaluation of Leukocyte Response due to Implant of a Controlled Released Drug Delivery System of Chitosan Hydrogel Loaded with Selenium Nanoparticle in Rats with Experimental Spinal Cord Injury." Tabari Biomedical Student Research Journal, Vol. 4 (No. 2), pp. 1-16, (2022).
16- Tae‐Joon Cho, Louis C Gerstenfeld, and Thomas A Einhorn, "Differential temporal expression of members of the transforming growth factor β superfamily during murine fracture healing." Journal of bone and mineral research, Vol. 17 (No. 3), pp. 513-20, (2002).
17- Rozalia Dimitriou, Eleftherios Tsiridis, and Peter V Giannoudis, "Current concepts of molecular aspects of bone healing." Injury, Vol. 36 (No. 12), pp. 1392-404, (2005).
18- Lutz Claes, Stefan Recknagel, and Anita Ignatius, "Fracture healing under healthy and inflammatory conditions." Nature Reviews Rheumatology, Vol. 8 (No. 3), pp. 133-43, (2012).
19- Jukka Pajarinen et al., "Mesenchymal stem cell-macrophage crosstalk and bone healing." Biomaterials, Vol. 196pp. 80-89, (2019).
20- Bilal Osta, Giulia Benedetti, and Pierre Miossec, "Classical and paradoxical effects of TNF-α on bone homeostasis." Frontiers in immunology, Vol. 5p. 48, (2014).
21- Sheeny K Lan Levengood and Miqin Zhang, "Chitosan-based scaffolds for bone tissue engineering." Journal of Materials Chemistry B, Vol. 2 (No. 21), pp. 3161-84, (2014).
22- Jayachandran Venkatesan and Se-Kwon Kim, "Chitosan composites for bone tissue engineering—an overview." Marine drugs, Vol. 8 (No. 8), pp. 2252-66, (2010).
23- Yang-Jo Seol et al., "Chitosan sponges as tissue engineering scaffolds for bone formation." Biotechnology letters, Vol. 26 (No. 13), pp. 1037-41, (2004).
24- RAA Muzzarelli et al., "Stimulatory effect on bone formation exerted by a modified chitosan." Biomaterials, Vol. 15 (No. 13), pp. 1075-81, (1994).
25- Piet Geusens, Pieter J Emans, Joost JA de Jong, and Joop van den Bergh, "NSAIDs and fracture healing." Current opinion in rheumatology, Vol. 25 (No. 4), pp. 524-31, (2013).
26- Alexander Beck, Khaled Salem, Gert Krischak, Lothar Kinzl, Mark Bischoff, and Andreas Schmelz, "Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics effects on bone healing." Operative Orthopadie und Traumatologie, Vol. 17 (No. 6), pp. 569-78, (2005).
27- Christopher J Richards, Kenneth W Graf, and Rakesh P Mashru, "The effect of opioids, alcohol, and nonsteroidal anti-inflammatory drugs on fracture union." Orthopedic Clinics, Vol. 48 (No. 4), pp. 433-43, (2017).
28- Robert W van Esch, Maurice M Kool, and Saskia van As, "NSAIDs can have adverse effects on bone healing." Medical hypotheses, Vol. 81 (No. 2), pp. 343-46, (2013).
29- J David Clark et al., "Morphine reduces local cytokine expression and neutrophil infiltration after incision." Molecular pain, Vol. 3pp. 1744-8069-3-28, (2007).
30- Yong-min Liu, Sheng-mei Zhu, Kui-rong Wang, Zhi-ying Feng, and Qing-lian Chen, "Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain." Journal of Zhejiang University SCIENCE B, Vol. 9 (No. 11), pp. 895-902, (2008).
31- Flaminia Coluzzi, Maria Sole Scerpa, and Marco Centanni, "The effect of opiates on bone formation and bone healing." Current Osteoporosis Reports, Vol. 18 (No. 3), pp. 325-35, (2020).
32- Alexander Beck, Khaled Salem, Gert Krischak, Lothar Kinzl, Mark Bischoff, and Andreas Schmelz, "Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics effects on bone healing." Operative Orthopadie und Traumatologie, Vol. 17 (No. 6), pp. 569-78, (2005).
33- Larissa B Cardozo et al., "Evaluation of the effects of methadone and tramadol on postoperative analgesia and serum interleukin-6 in dogs undergoing orthopaedic surgery." BMC veterinary research, Vol. 10 (No. 1), pp. 1-7, (2014).
| Files | ||
| Issue | Vol 10 No 3 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/fbt.v10i3.13163 | |
| Keywords | ||
| Bone Healing Inflammation Methadone Piroxicam Chitosan | ||
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How to Cite
1.
Khosravian P, Javdani M, Masoudi M, Mohebi A, Bigham Sadegh A, Barzegar A. Preparation and Administration of a Controlled-Release Delivery System of Chitosan Hydrogel loaded with Methadone and Piroxicam in Experimental Defect of Tibial in Rats; Histopathological Evaluation. Frontiers Biomed Technol. 2023;10(3):327-338.
