Abstract
Some species of the Berberidaceae family and natural biopolymer chitosan have good effects on wound healing. In this research, a new formulation of chitosan hydrogel containing alcoholic root extract of Berberis integerrima (Chi-BIE) was designed and evaluated for the treatment of full-thickness skin wounds in an animal model. Alcoholic extract of Berberis integerrima root (BIE) was prepared, and its total amount of berberine was determined using UV/visible spectroscopy. Chitosan gel containing 10 and 20% BIE was prepared, and their extract release profile was assayed. The antimicrobial activity of Chi-BIE was investigated by the minimum inhibitory concentration assay. Finally, the efficiency of Chi-BIE formulations on the full-thickness wound healing was physically and histologically evaluated in an animal model. BIE was successfully loaded into the chitosan hydrogel and showed a burst release of extract during the first 4 h (60%) followed by a sustained release. Formulation of BIE in chitosan hydrogel could increase the antimicrobial activity of chitosan and BIE alone against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilius, Escherichia coli, and Candida albicans. Chi-20% BIE indicated more antimicrobial activity compared to Chi-10%BIE. Formulation of BIE in chitosan hydrogel could increase the wound healing effects of chitosan and BIE alone. Chi-20% BIE had a faster restorative effect than other treatment groups due to more formation of epithelial tissue and faster maturation of bud tissue. Based on the results of this study, the chitosan hydrogel containing BIE is proposed as a suitable dressing for wound-healing.
Similar content being viewed by others
References
G. C. Gurtner, S. Werner, Y. Barrandon, and M. T. Longaker, Nature, 453, 314 (2008).
K. Lau, R. Paus, S. Tiede, P. Day, and A. Bayat, Exp. Dermatol., 18, 921 (2009).
A. N. Dehkordi, F. M. Babaheydari, M. Chehelgerdi, and S. R. Dehkordi, Stem Cell Res. Ther., 10, 111 (2019).
L. E. Dickinson and S. Gerecht, Front. Physiol., 7, 341 (2016).
D. Duscher, J. Barrera, V. W. Wong, Z. N. Maan, A. J. Whittam, M. Januszyk, and G. C. Gurtner, Gerontology, 62, 216 (2016).
N. J. Turner and S. F. Badylak, Adv. Wound Care, 4, 490 (2015).
A. Shedoeva, D. Leavesley, Z. Upton, and C. Fan, Evid. Based Complement Alternat Med., 2019, 2684108 (2019).
H. Dong, Y. Zhao, L. Zhao, and F. Lu, Planta Medica, 79, 437 (2013).
M. Fatehi, T. M. Saleh, Z. Fatehi-Hassanabad, K. Farrokhfal, M. Jafarzadeh, and S. Davodi, J. Ethnopharmacol., 102, 46 (2005).
Sh. Gorjian, T. Tavakkoli Hashjin, M. H. Khoshtaghaza, and A. Nikbakht, J. Agric. Sci. Technol., 13, 303 (2011).
A. Asif, G. Kakub, S. Mehmood, R. Khunum, and M. Gulfraz, Phytother. Res., 21, 589 (2007).
P. Mansoureh, S. Abdolhossein, and H. Vida, J. Chem. Health Risks, 6, 319 (2016).
S. Fateh, S. P. Dibazar, and S. Daneshmandi, Future Sci. OA, 1, FSO49 (2015).
J. L. Sun, Y. L. Hu, D. Y. Wang, B. K. Zhang, and J. G. Liu, Vaccine, 24, 2343 (2006).
D. Song, J. Hao, and D. Fan, Front. Med., 14, 564 (2020).
N. Singh and B. Sharma, Front. Mol. Biosci., 5, 21 (2018).
B. E. A. Abadi, D. S. Moss, and R. A. Palmer, J. Crystallogr. Spectrosc. Res., 14, 269 (1984).
J. Schor, Nat. Med. J., 4, 112 (2012).
H. Xu, X.-D. Yuan, B.-D. Shen, J. Han, Q.-Y. Lv, L. Dai, M.-G. Lin, C. Yu, J.-X. Bai, and H.-L. Yuan, J. Biomater. Appl., 28, 1376 (2014).
M. Singh, S. Srivastava, and A. K. Rawat, Fitoterapia, 78, 574 (2007).
G. Azimi, A. Hakakian, M. Ghanadian, A. Joumaa, and S. Alamian, Res. Pharm. Sci., 13, 149 (2018).
T. Dai, M. Tanaka, Y.-Y. Huang, and M. R. Hamblin, Expert Rev. Anti Infect. Ther., 9, 857 (2011).
F. Tao, S. Ma, H. Tao, L. Jin, Y. Luo, J. Zheng, W. Xiang, and H. Deng, Carbohydr. Polym., 251, 117063 (2021).
F. S. Rezaei, F. Sharifianjazi, A. Esmaeilkhanian, and E. Salehi, Carbohydr. Polym., 273, 118631 (2021).
M. Kołodziejska, K. Jankowska, M. Klak, and M. Wszoła, Nanomaterials (Basel), 11, 3019 (2021).
L. M. Hemmingsen, N. Škalko-Basnet, and M. W. Jøraholmen, Mar. Drugs, 19, 697 (2021).
P. Feng, Y. Luo, C. Ke, H. Qiu, W. Wang, Y. Zhu, R. Hou, L. Xu, and S. Wu, Front. Bioeng. Biotechnol., 9, 650598 (2021).
R. Jayakumar, M. Prabaharan, P. T. S. Kumar, S. V. Nair, and H. Tamura, Biotechnol. Adv., 29, 322 (2011).
M. Zubair, A. Malik, and J. Ahmad, Foot (Edinb), 21, 6 (2011).
M. Amidi, E. Mastrobattista, W. Jiskoot, and W. E. Hennink, Adv. Drug Deliv. Rev., 62, 59 (2010).
J. Wang, Y. Jiang, B. Wang, and N. Zhang, J. Sep. Sci., 42, 1794 (2019).
F. Kalalinia, N. Amiri, N. Mehrvarzian, B. S. F. Bazzaz, M. Iranshahi, A. Shahroodi, S. Arabzadeh, M. Abbaspour, S. B. Aaval, and J. Movaffagh, Iran. J. Basic Med. Sci., 23, 1085 (2020).
F. Kalalinia, Z. Taherzadeh, N. Jirofti, N. Amiri, N. Foroghinia, M. Beheshti, B. S. F. Bazzaz, M. Hashemi, A. Shahroodi, E. Pishavar, S. A. S. Tabassi, and J. Movaffagh, Int. J. Biol. Macromol., 177, 100 (2021).
N. Jirofti, M. Golandi, J. Movaffagh, F. S. Ahmadi, and F. Kalalinia, ACS Biomater. Sci. Eng., 7, 3886 (2021).
N. Amiri, S. Ajami, A. Shahroodi, N. Jannatabadi, S. A. Darban, B. S. F. Bazzaz, E. Pishavar, F. Kalalinia, and J. Movaffagh, Int. J. Biol. Macromol., 162, 645 (2020).
M. Jahandideh, H. Hajimehdipoor, S. A. Mortazavi, A. Dehpour, and G. Hassanzadeh, Iran. J. Pharm. Res., 15(Suppl), 149 (2016).
R. Zhou, C. Xiang, G. Cao, H. Xu, Y. Zhang, H. Yang, and J. Zhang, Clin. Sci. (Lond), 135, 613 (2021).
P. Zhang, L. He, J. Zhang, X. Mei, Y. Zhang, and H. Tian, Colloids Surf. B Biointerfaces, 187, 110647 (2020).
M. S. Islam, M. S. Rahman, T. Ahmed, S. Biswas, P. Haque, M. M. Rahman, in Handbook of Chitin and Chitosan, S. Gopi, S. Thomas, and A. Pius, Eds., Elsevier, Amsterdam, 3, 721 (2020).
N. Gokarneshan, Global J. Addict. Rehab. Medicine, 4, 61 (2017).
J.-L. Jin, G.-Q. Hua, M. Zhen, and P.-J. Gao, Chin. Herb. Medicines, 3, 27 (2011).
M. E. Cam, S. Yildiz, H. Alenezi, S. Cesur, G. S. Ozcan, G. Erdemir, U. Edirisinghe, D. Akakin, D. S. Kuruca, L. Kabasakal, O. Gunduz, and M. Edirisinghe, J. R. Soc. Interface, 17, 20190712 (2020).
M. Imenshahidi and H. Hosseinzadeh, Phytother. Res., 30, 1745 (2016).
J. Villinski, E. Dumas, H.-B. Chai, J. Pezzuto, C. Angerhofer, and S. Gafner, Pharm. Biol., 41, 551 (2003).
D. K. Bhandari, G. Nath, A. B. Ray, and P. V. Tewari, Pharm. Boil., 38, 254 (2000).
J. M. Boberek, J. Stach, and L. Good, PloS One, 5, e13745 (2010).
M. Cernáková and D. Kostálová, Folia Microbiol., 47, 375 (2002).
S. Shaygan, S. Fakhri, G. Bahrami, K. Rashidi, and M. H. Farzaei, Adv. Pharmacol. Pharm. Sci., 2021, 6697174 (2021).
M. K. Lambebo, Z. D. Kifle, T. B. Gurji, and J. S. Yesuf, J. Exp. Pharmacol., 13, 677 (2021).
J. Li and S. Zhuang, Eur. Polym. J., 138, 109984 (2020).
J. Bao, B. Yang, Y. Sun, Y. Zu, and Y. Deng, J. Biomed. Nanotechnol., 9, 1173 (2013).
M. Rahimi, S. J. S. Tabaei, S. A. Ziai, and M. Sadri, Iran. J. Med. Sci., 45, 286 (2020).
H. Samadian, S. Zamiri, A. Ehterami, S. Farzamfar, A. Vaez, H. Khastar, M. Alam, A. Ai, H. Derakhshankhah, Z. Allahyari, A. Goodarzi, and M. Salehi, Sci. Rep., 10, 8312 (2020).
G. Amato, M. A. Grimaudo, C. Alvarez-Lorenzo, A. Concheiro, C. Carbone, A. Bonaccorso, G. Puglisi, and T. Musumeci, Pharmaceutics, 13, 34 (2020).
P. Zhang, L. He, J. Zhang, X. Mei, Y. Zhang, H. Tian, and Z. Chen, Colloids Surf. B Biointerfaces, 187, 110647 (2020).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of intrest statement: The authors declare that there are no conflicts of interest
Additional information
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Acknowledgment: The authors would like to express their sincere grateful to the Research Council of Mashhad University of Medical Sciences, Mashhad, Iran, for approval and financial support of this project. The results described in this paper were part of Pharm.D thesis of Mobina Razi.
Rights and permissions
About this article
Cite this article
Hashemi, M., Kalalinia, F., Razi, M. et al. Evaluation of the Efficiency of Chitosan Hydrogel Containing Berberis integerrima Root Extract on a Full-Thickness Skin Wound in a Rat Model. Macromol. Res. 30, 527–535 (2022). https://doi.org/10.1007/s13233-022-0043-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13233-022-0043-7