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Dual effect of procaine-loaded pectin hydrogels: pain management and in vitro wound healing

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Abstract

This study aims to develop procaine-loaded pectin hydrogels for both local anesthetic delivery and wound healing. We investigated the effects of initial drug concentration, pH of initial drug solution, and drying temperature of hydrogel on the drug release behavior of hydrogels. Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy were used for their characterization. Their swelling percentage, drug loading, and drug release behaviors were determined. Toxic effects of selected hydrogels on the wound healing ability of PCS-201-012 human dermal fibroblast cells and wound dressing properties were also investigated. According to our results, the hydrogels did not affect cell migration. Initial drug concentration, pH of initial drug solution, and drying temperature of hydrogels are crucial on procaine release behavior of pectin-based hydrogels.

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References

  1. Bagshaw KR, Hanenbaum CL, Carbone EJ, Lo KW, Laurencin CT, Walker J, Nair LS (2015) Pain management via local anesthetics and responsive hydrogels. Ther Deliv 6:165–176. https://doi.org/10.4155/tde.14.95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hirata K, Helal F, Hadgraft J, Lane ME (2013) Formulation of carbenoxolone for delivery to the skin. Int J Pharm 448:360–365. https://doi.org/10.1016/j.ijpharm.2013.03.045

    Article  CAS  PubMed  Google Scholar 

  3. Saxena P, Chandra A, Gupta S, Newaskar V (2013) Advances in dental local anesthesia techniques and devices: an update. Natl J Maxillofac Surg 4:19. https://doi.org/10.4103/0975-5950.117873

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hirata K, Mohammed D, Hadgraft J, Lane ME (2014) Influence of lidocaine hydrochloride and penetration enhancers on the barrier function of human skin. Int J Pharm 477:416–420. https://doi.org/10.1016/j.ijpharm.2014.10.012

    Article  CAS  PubMed  Google Scholar 

  5. Beiranvand S, Eatemadi A, Karimi A (2016) New updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles. Nanoscale Res Lett 11:307. https://doi.org/10.1186/s11671-016-1520-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ustundag Okur N, Çağlar EŞ, Arpa MD, Karasulu Y (2017) Preparation and evaluation of novel microemulsion-based hydrogels for dermal delivery of benzocaine. Pharm Dev Technol 22:500–510. https://doi.org/10.3109/10837450.2015.1131716

    Article  CAS  PubMed  Google Scholar 

  7. Kurecic M, Maver T, Virant N, Ojstrsek A, Gradisnik L, Hribernik S, Kolar M, Maver U, Kleinschek KS (2018) A multifunctional electrospun and dual nano-carrier biobased system for simultaneous detection of pH in the wound bed and controlled release of benzocaine. Cellulose 25:7277–7297. https://doi.org/10.1007/s10570-018-2057-z

    Article  CAS  Google Scholar 

  8. Morris T, Appleby R (1980) Retardation of wound healing by procaine. Br J Surg 67:391–392. https://doi.org/10.1002/bjs.1800670603

    Article  CAS  PubMed  Google Scholar 

  9. Chvapil M, Hameroff S, O'Dea K, Peacock EE (1979) Local anesthetics and wound healing. J Surg Res 27:367–371. https://doi.org/10.1016/0022-4804(79)90155-0

    Article  CAS  PubMed  Google Scholar 

  10. Wakamatsu T (1992) Effects of local anesthetics on healing process of extraction wound in rats with reference to effects of epinephrine, Kokubyo Gakkai zasshi. J Stomatol Soc Jpn 59:613–630

    Article  CAS  Google Scholar 

  11. Rodrigues FV, Hochman B, Wood VT, Simões MJ, Juliano Y, Ferreira LM (2011) Effects of lidocaine with epinephrine or with buffer on wound healing in rat skin. Wound Repair Regener 19:223–228. https://doi.org/10.1111/j.1524-475X.2010.00654.x

    Article  Google Scholar 

  12. Zeren S, Kesici S, Kesici U, Isbilir S, Turkmen UA, Ulusoy H, Karpuz V, Ozcan O, Polat E, Ipcioglu OM, Sari MK (2013) Effects of levobupivacaine on wound healing. Anesth Analg 116:495–499. https://doi.org/10.1213/ANE.0b013e318273f48e

    Article  CAS  PubMed  Google Scholar 

  13. Doǧan N, Üçok C, Korkmaz C, Üçok Ö, Karasu HA (2003) The effects of articaine hydrochloride on wound healing: an experimental study. J Oral Maxillofac Surg 61:1467–1470. https://doi.org/10.1016/j.joms.2003.05.002

    Article  PubMed  Google Scholar 

  14. Akcal A, Karsidag S, Yildiz K, Yesiloglu N, Akcal M, Kabukcuoglu F (2015) The effects of locally applied procaine on wound healing. Arch Clin Exp Surg 4:41–45. https://doi.org/10.5455/aces.20140606054447

    Article  Google Scholar 

  15. Rezvanian M, Ahmad N, Amin MCIM, Ng SF (2017) Optimization, characterization, and in vitro assessment of alginate-pectin ionic cross-linked hydrogel film for wound dressing applications. Int J Biol Macromol 97:131–140. https://doi.org/10.1016/j.ijbiomac.2016.12.079

    Article  CAS  PubMed  Google Scholar 

  16. Johnson SM, Saint John BE, Dine AP (2008) Local anesthetics as antimicrobial agents: a review. Surg Infect (Larchmt) 9:205–213. https://doi.org/10.1089/sur.2007.036

    Article  Google Scholar 

  17. Culp WC, Culp WC (2011) Practical application of local anesthetics. J Vasc Interv Radiol 22:111–118. https://doi.org/10.1016/j.jvir.2010.10.005

    Article  PubMed  Google Scholar 

  18. Maver T, Hribernik S, Mohan T, Smrke DM, Maver U, Stana-Kleinschek K (2015) Functional wound dressing materials with highly tunable drug release properties. RSC Adv 5:77873–77884. https://doi.org/10.1039/c5ra11972c

    Article  CAS  Google Scholar 

  19. Xu K, Kleinbeck KR, Kao WJ (2012) Multifunctional biomaterial matrix for advanced wound healing. Adv Wound Care 1:75–80. https://doi.org/10.1089/wound.2011.0349

    Article  Google Scholar 

  20. Ninan N, Muthiah M, Yahaya NAB, Park IK, Elain A, Wong TW, Thomas S, Grohens Y (2014) Antibacterial and wound healing analysis of gelatin/zeolite scaffolds. Colloids Surf B Biointerfaces 115:244–252. https://doi.org/10.1016/j.colsurfb.2013.11.048

    Article  CAS  PubMed  Google Scholar 

  21. Rampino A, Borgogna M, Bellich B, Blasi P, Virgilio F, Cesàro A (2016) Chitosan–pectin hybrid nanoparticles prepared by coating and blending techniques. Eur J Pharm Sci 84:37–45. https://doi.org/10.1016/j.ejps.2016.01.004

    Article  CAS  PubMed  Google Scholar 

  22. Neufeld L, Bianco-Peled H (2017) Pectin–chitosan physical hydrogels as potential drug delivery vehicles. Int J Biol Macromol 101:852–861. https://doi.org/10.1016/j.ijbiomac.2017.03.167

    Article  CAS  PubMed  Google Scholar 

  23. Munarin F, Tanzi MC, Petrini P (2012) Advances in biomedical applications of pectin gels. Int J Biol Macromol 51:681–689. https://doi.org/10.1016/j.ijbiomac.2012.07.002

    Article  CAS  PubMed  Google Scholar 

  24. Esposito M, DiPierro P, Regalado-Gonzales C, Mariniello L, Giosafatto CVL, Porta R (2016) Polyamines as new cationic plasticizers for pectin-based edible films. Carbohydr Polym 153:222–228. https://doi.org/10.1016/j.carbpol.2016.07.087

    Article  CAS  PubMed  Google Scholar 

  25. Güner OZ, Cam C, Arabacioglu-Kocaaga B, Batirel S, Güner FS (2018) Theophylline-loaded pectin-based hydrogels. I. Effect of medium pH and preparation conditions on drug release profile. J Appl Polym Sci 135:46731. https://doi.org/10.1002/APP.46731

    Article  Google Scholar 

  26. Tan JP, Zeng AQ, Chang CC, Tam KC (2008) Release kinetics of procaine hydrochloride (PrHy) from pH-responsive nanogels: theory and experiments. Int J Pharm 357:305–313. https://doi.org/10.1016/j.ijpharm.2008.01.058

    Article  CAS  PubMed  Google Scholar 

  27. BS EN 12127:1998 (1998) Textiles fabrics determination of mass per unit area using small samples. British Standard Institute, London. ISBN 0-580-29132-4

    Google Scholar 

  28. BN EN ISO 9073-2:1997 (1997) Textiles, Test methods for nonwovens, part 2: determination of thickness. British Standard Institute, London

    Google Scholar 

  29. D522-93a, Standard test methods for mandrel bend test of attached organic coatings. American Society for Testing and Materials

  30. D2240-97 standard test method for rubber property—durometer hardness. American Society for Testing and Materials

  31. BS EN 13726-1:2002 (2002) Test methods for primary wound dressings. Aspect of absorbency, BSI. British Standard Institute, London. ISBN 0-580-39510-3

    Google Scholar 

  32. Parsons D, Bowler PG, Myles V, Jones S (2005) Silver antimicrobial dressings in wound management: a comparison of antibacterial, physical, and chemical characteristics. Wounds 17:222–232

    Google Scholar 

  33. BS EN 13726-2:2001 (2001) Test method for primary wound dressing. Part 1: aspect of absorbency, section 3.6, dispersion characteristics. British Standard Institute, London

    Google Scholar 

  34. ASTM E96 Standard Test Methods for water vapor transmission of materials. American Society for Testing and Materials

  35. Du WX, Olsen CW, Avena-Bustillos RJ, McHugh TH, Levin CE, Mandrell R, Friedman M (2009) Antibacterial effects of allspice, garlic, and oregano essential oils in tomato films determined by overlay and vapor-phase methods. J Food Sci 74:M390–M397. https://doi.org/10.1111/j.1750-3841.2009.01289.x

    Article  CAS  PubMed  Google Scholar 

  36. Das B, Nayak AK, Nanda U (2013) Topical gels of lidocaine HCl using cashew gum and Carbopol 940: preparation and in vitro skin permeation. Int J Biol Macromol 62:514–517. https://doi.org/10.1016/j.ijbiomac.2013.09.049

    Article  CAS  PubMed  Google Scholar 

  37. Shin SC, Cho CW, Yang KH (2004) Development of lidocaine gels for enhanced local anesthetic action. Int J Pharm 287:73–78. https://doi.org/10.1016/j.ijpharm.2004.08.012

    Article  CAS  PubMed  Google Scholar 

  38. Latif IA, Abdullah HM, Saleem MH (2016) Electrical and swelling study of different prepared hydrogel. Am J Polym Sci 6:50–57. https://doi.org/10.5923/j.ajps.20160602.04

    Article  CAS  Google Scholar 

  39. Mishra RK, Datt M, Banthia AK (2008) Synthesis and characterization of pectin/PVP hydrogel membranes for drug delivery system. AAPS Pharm Sci Technol 9:395–403. https://doi.org/10.1208/s12249-008-9048-6

    Article  CAS  Google Scholar 

  40. Fuliaş A, Ledeţi I, Vlase G, Popoiu C, Hegheş A, Bilanin M, Vlase T, Gheorgheosu D, Craina M, Ardelean S, Ferechide D, Mǎrginean O, Moş L (2013) Thermal behaviour of procaine and benzocaine. Part II: compatibility study with some pharmaceutical excipients used in solid dosage forms. Chem Cent J 7:1–10. https://doi.org/10.1186/1752-153X-7-140

    Article  Google Scholar 

  41. Pourjavadi A, Barzegar S (2009) Synthesis and evaluation of pH and thermosensitive pectin-based superabsorbent hydrogel for oral drug delivery systems. Starch/Staerke 61:161–172. https://doi.org/10.1002/star.200800063

    Article  CAS  Google Scholar 

  42. Namazi H, Rakhshaei R, Hamishehkar H, Kafil HS (2016) Antibiotic loaded carboxy methyl cellulose/MCM-41 nanocomposite hydrogel films as potential wound dressing. Int J Biol Macromol 85:327–334. https://doi.org/10.1016/j.ijbiomac.2015.12.076

    Article  CAS  PubMed  Google Scholar 

  43. Opanasopit P, Apirakaramwong A, Ngawhirunpat T, Rojanarata T, Ruktanonchai U (2008) Development and characterization of pectinate micro/nanoparticles for gene delivery. AAPS Pharm Sci Technol 9:67–74. https://doi.org/10.1208/s12249-007-9007-7

    Article  CAS  Google Scholar 

  44. Tan JP, Goh CH, Tam KC (2007) Comparative drug release studies of two cationic drugs from pH-responsive nanogels. Eur J Pharm Sci 32:340–348. https://doi.org/10.1016/j.ejps.2007.08.010

    Article  CAS  PubMed  Google Scholar 

  45. Samanta HS, Ray SK (2014) Controlled release of tinidazole and theophylline from chitosan based composite hydrogels. Carbohydr Polym 106:109–120. https://doi.org/10.1016/j.carbpol.2014.01.097

    Article  CAS  PubMed  Google Scholar 

  46. Sriamornsak P (1999) Effect of calcium concentration, hardening agent and drying condition on release characteristics of oral proteins from calcium pectinate gel beads. Eur J Pharm Sci 8:221–227. https://doi.org/10.1016/S0928-0987(99)00010-X

    Article  CAS  PubMed  Google Scholar 

  47. De Cicco F, Reverchon E, Adami R, Auriemma G, Russo P, Calabrese EC, Porta A, Aquino RP, Del Gaudio P (2014) In situ forming antibacterial dextran blend hydrogel for wound dressing: SAA technology vs. spray drying. Carbohydr Polym 101:1216–1224. https://doi.org/10.1016/j.carbpol.2013.10.067

    Article  CAS  PubMed  Google Scholar 

  48. Lin LS, Yuen HK, Varner JE (1991) Differential scanning calorimetry of plant cell walls. Proc Natl Acad Sci USA 88:2241–2243. https://doi.org/10.1073/pnas.88.6.2241

    Article  CAS  PubMed  Google Scholar 

  49. Physicochemical properties of drugs. In: Donald C (ed) Essentials of pharmaceutical chemistry (2012). Sample chapter copyright Pharmaceutical Press, pp 57–79. https://www.pharmpress.com/files/docs/EssentialsPharmaceuticalChemistry_Sample(2).pdf. Accessed 24 Dec 2018

  50. Shilpa A, Agrawal SS, Ray AR (2003) Controlled delivery of drugs from alginate matrix. J Macromol Sci C Polym Rev 43(2):187–221. https://doi.org/10.1081/MC-12002016

    Article  Google Scholar 

  51. Segi N, Yotsuyanagi T, Ikeda K (1989) Interaction of calcium-alginate gel beads with propranolol. Chem Pharm Bull 37(11):3092–3095. https://doi.org/10.1248/cpb.37.3092

    Article  CAS  Google Scholar 

  52. You JO, Park SB, Park HY, Haam S, Chung CH, Kim WS (2001) Preparation of regular sized Ca-alginate microspheres using membrane emulsification method. J Microencapsul 18(4):521–532. https://doi.org/10.1248/cpb.37.3092

    Article  CAS  PubMed  Google Scholar 

  53. Zhila I, Adeleh D, Akbar AS, Sawyer L (2016) β-Lactoglobulin–pectin nanoparticle-based oral drug delivery system for potential treatment of colon cancer. Chem Biol Drug Des 88:209–216. https://doi.org/10.1111/cbdd.12748

    Article  CAS  Google Scholar 

  54. Skorkowska-Telichowska K, Czemplik M, Kulma A, Szopa J (2013) The local treatment and available dressings designed for chronic wounds. J Am Acad Dermatol 68:e117. https://doi.org/10.1016/j.jaad.2011.06.028

    Article  CAS  PubMed  Google Scholar 

  55. Jantrawut P, Bunrueangtha J, Suerthong J (2019) Fabrication and characterization of low methoxyl pectin/gelatin/carboxymethyl cellulose absorbent hydrogel film for wound dressing applications. Materials 12:1628. https://doi.org/10.3390/ma12101628

    Article  CAS  PubMed Central  Google Scholar 

  56. Uzun M, Anand SC, Shah AT (2013) In vitro characterization and evaluation of different types of wound dressing materials. J Biomed Eng Technol 1(2013):1–7

    Google Scholar 

  57. Balakrishnan B, Mohanty M, Umashankar PR, Jayakrishnan A (2005) Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials 26:6335–6342. https://doi.org/10.1016/j.biomaterials.2005.04.012

    Article  CAS  PubMed  Google Scholar 

  58. Shahzad A, Khan A, Afzal Z, Umer MF, Khan J, Khan GM (2019) Formulation development and characterization of cefazolin nanoparticles-loaded cross-linked films of sodium alginate and pectin as wound dressings. Int J Biol Macromol 124:255–269. https://doi.org/10.1016/j.ijbiomac.2018.11.090

    Article  CAS  PubMed  Google Scholar 

  59. Rezvanian M, Ahmad N, Mohd Amin MCI, Ng SF (2017) Optimization, characterization, and in vitro assessment of alginate-pectin ionic cross-linked hydrogel film for wound dressing applications. Int J Biol Macromol 97:131–140. https://doi.org/10.1016/j.ijbiomac.2016.12.079

    Article  CAS  PubMed  Google Scholar 

  60. Alavi T, Rezvanian M, Ahmad N, Mohamad N, Ng SF (2019) Pluronic-F127 composite film loaded with erythromycin for wound application: formulation, physicomechanical and in vitro evaluations. Drug Deliv Transl Res 9:508–519. https://doi.org/10.1007/s13346-017-0450-z

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We sincerely thank Herbstreith & Fox company for providing low-methylated pectin. This work was funded by The Scientific and Technological Research Council of Turkey (TUBITAK) with 115M439 of Project Number.

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Authors and Affiliations

  1. Department of Chemical Engineering, Istanbul Technical University, 34469, Maslak, Istanbul, Turkey

    Seniz Rodoplu, Bengi Ezgi Celik, Banu Kocaaga, Cenk Ozturk & F. Seniha Guner

  2. Department of Medical Biochemistry, School of Medicine, Marmara University, 34854, Maltepe, Istanbul, Turkey

    Saime Batirel

  3. Department of Food Engineering, Istanbul Technical University, 34469, Maslak, Istanbul, Turkey

    Deniz Turan

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  1. Seniz Rodoplu
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Rodoplu, S., Celik, B.E., Kocaaga, B. et al. Dual effect of procaine-loaded pectin hydrogels: pain management and in vitro wound healing. Polym. Bull. 78, 2227–2250 (2021). https://doi.org/10.1007/s00289-020-03210-7

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