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Tamarind/β-CD-g-poly (MAA) pH responsive hydrogels for controlled delivery of Capecitabine: fabrication, characterization, toxicological and pharmacokinetic evaluation

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Abstract

The present study was aimed for controlled delivery of capecitabine, an anticancer drug used to treat colorectal cancer. Smart pH responsive tamarind/-CD-g-poly (MAA) hydrogels were developed using the free radical polymerization process to overcome the constraints of capecitabine such as short plasma half-life, low bioavailability, and high dose frequency. The developed network system was evaluated for different characterizations including equilibrium swelling (%), drug loading efficiency (%), thermal behavior, elemental composition, morphology, complexation of components and release kinetics. Furthermore, safety profile of developed network was validated by acute oral toxicity studies and pharmacokinetic parameters were determined by carrying in-vivo studies in healthy rabbits. The grafted system proved to be thermally stable as confirmed by DSC and TGA analysis. While successful grafting, compatibility of hydrogel components and amorphous dispersion of drug within the network were shown by FTIR analysis and XRD studies. Significantly higher swelling and drug release were observed at pH 7.4 than at pH 1.2, evidencing pH responsive character of hydrogels. Maximum drug release of 94.3% was shown over period of 30 h demonstrating the controlled release profile of polymeric network. Toxicity evaluations revealed good safety profile and biocompatibility of hydrogels. Moreover, in-vivo studies showed sustained release profile of capecitabine as proved by significant increase in its half-life (13 h) and AUC (42.88 µg.h/ml) when administered as hydrogels. Hence, tamarind/β-CD-g-poly (MAA) hydrogels are strongly recommended to be employed as biocompatible pH responsive carrier system and can be utilized for controlled and targeted delivery of drugs.

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References

  1. Li J, Mooney DJ (2016) Designing hydrogels for controlled drug delivery. Nat Rev Mater 1(12):1–17

    Article  Google Scholar 

  2. Soni G, Yadav KS (2016) Nanogels as potential nanomedicine carrier for treatment of cancer: A mini review of the state of the art. Saudi Pharmaceutical Journal 24(2):133–139

    Article  Google Scholar 

  3. Bhattarai N, Gunn J, Zhang M (2010) Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev 62(1):83–99

    Article  CAS  Google Scholar 

  4. Sharpe LA, Daily AM, Horava SD, Peppas NA (2014) Therapeutic applications of hydrogels in oral drug delivery. Expert Opin Drug Deliv 11(6):901–915

    Article  CAS  Google Scholar 

  5. Mishra B, Upadhyay M, Reddy Adena S, Vasant B, Muthu M (2017) Hydrogels: an introduction to a controlled drug delivery device, synthesis and application in drug delivery and tissue engineering. Austin J Biomed Eng 4(1):1037–1049

    Google Scholar 

  6. Lu Y, Sturek M, Park K (2014) Microparticles produced by the hydrogel template method for sustained drug delivery. Int J Pharm 461(1–2):258–269

    Article  CAS  Google Scholar 

  7. Afshar M, Dini G, Vaezifar S, Mehdikhani M, Movahedi B (2020) Preparation and characterization of sodium alginate/polyvinyl alcohol hydrogel containing drug-loaded chitosan nanoparticles as a drug delivery system. J Drug Deliv Sci Technol 56:101530

    Article  CAS  Google Scholar 

  8. Pakizeh M, May P, Matthias M, Ulbricht M (2020) Preparation and characterization of polyzwitterionic hydrogel coated polyamide-based mixed matrix membrane for heavy metal ions removal. J Appl Polym Sci 137(48):49595

    Article  CAS  Google Scholar 

  9. Junior CR, Fernandes RdS, de Moura MR, Aouada FA (2020) On the preparation and physicochemical properties of pH-responsive hydrogel nanocomposite based on poly (acid methacrylic)/laponite RDS. Mater Today Commun 23:100936

    Article  CAS  Google Scholar 

  10. Jiang Q, Wang J, Tang R, Zhang D, Wang X (2016) Hypromellose succinate-crosslinked chitosan hydrogel films for potential wound dressing. Int J Biol Macromol 91:85–91

    Article  CAS  Google Scholar 

  11. Shaw GS, Uvanesh K, Gautham S et al (2015) Development and characterization of gelatin-tamarind gum/carboxymethyl tamarind gum based phase-separated hydrogels: A comparative study. Des Monomers Polym 18(5):434–450

    Article  CAS  Google Scholar 

  12. Nayak AK, Pal D (2017) Tamarind seed polysaccharide: an emerging excipient for pharmaceutical use. Indian J Pharm Educ Res 51:S136-146

    Article  CAS  Google Scholar 

  13. Minhas MU, Ahmad M, Khan S, Ali L, Sohail M (2016) Synthesis and characterization of β-cyclodextrin hydrogels: crosslinked polymeric network for targeted delivery of 5-fluorouracil. Drug Deliv 9(10)

  14. Malik NS, Ahmad M, Minhas MU (2017) Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir. PLoS ONE 12(2):e0172727

    Article  Google Scholar 

  15. Abderaman MB, Gueye EH, Dione AN, Diouf AA, Faye O, Beye AC (2018) A molecular dynamics study on the miscibility of polyglycolide with different polymers. Int J Mater Sci Appl 7:126–132

    CAS  Google Scholar 

  16. Machackova M, Tokarsky J, Capkova P (2013) A simple molecular modeling method for the characterization of polymeric drug carriers. Eur J Pharm Sci 48:316–322

    Article  CAS  Google Scholar 

  17. Kashirina A, Yao Y, Liu Y, Leng J (2019) Biopolymers as bone substitutes: A review. Biomater Sci 7:3961–3983

    Article  CAS  Google Scholar 

  18. Meulenaar J, Beijnen JH, Schellens JH, Nuijen B (2013) Slow dissolution behaviour of amorphous capecitabine. Int J Pharm 441(1–2):213–217

    Article  CAS  Google Scholar 

  19. Agnihotri SA, Aminabhavi TM (2006) Novel interpenetrating network chitosan-poly (ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. Int J Pharm 324(2):103–115

    Article  CAS  Google Scholar 

  20. Taleblou N, Sirousazar M, Hassan ZM, Khaligh SG (2020) Capecitabine-loaded anti-cancer nanocomposite hydrogel drug delivery systems: In vitro and in vivo efficacy against the 4T1 murine breast cancer cells. J Biomater Sci Polym Ed 31:72–92

    Article  CAS  Google Scholar 

  21. Upadhyay M, Adena SK, Vardhan H, Yadav SK, Mishra B (2018) Development of biopolymers based interpenetrating polymeric network of capecitabine: a drug delivery vehicle to extend the release of the model drug. Int J Biol Macromol 115:907–919

    Article  CAS  Google Scholar 

  22. Nandi G, Changder A, Ghosh LK (2019) Graft-copolymer of polyacrylamide-tamarind seed gum: Synthesis, characterization and evaluation of flocculating potential in peroral paracetamol suspension. Carbohyd Polym 215:213–225

    Article  CAS  Google Scholar 

  23. García J, Ruiz-Durántez E, Valderruten N (2017) Interpenetrating polymer networks hydrogels of chitosan and poly (2-hydroxyethyl methacrylate) for controlled release of quetiapine. React Funct Polym 117:52–59

    Article  Google Scholar 

  24. Qi X, Li J, Wei W et al (2017) Cationic Salecan-based hydrogels for release of 5-fluorouracil. RSC Adv 7(24):14337–14347

    Article  CAS  Google Scholar 

  25. Afinjuomo F, Fouladian P, Parikh A, Barclay TG, Song Y, Garg S (2019) Preparation and characterization of oxidized inulin hydrogel for controlled drug delivery. Pharmaceutics 11(7):356

    Article  CAS  Google Scholar 

  26. Mandal B, Ray SK (2014) Swelling, diffusion, network parameters and adsorption properties of IPN hydrogel of chitosan and acrylic copolymer. Mater Sci Eng C 44:132–143

    Article  CAS  Google Scholar 

  27. Che Y, Li D, Liu Y et al (2016) Physically cross-linked pH-responsive chitosan-based hydrogels with enhanced mechanical performance for controlled drug delivery. RSC Adv 6(107):106035–106045

    Article  CAS  Google Scholar 

  28. Chaves LL, Silveri A, Vieira AC et al (2019) pH-responsive chitosan based hydrogels affect the release of dapsone: design, set-up, and physicochemical characterization. Int J Biol Macromol 133:1268–1279

    Article  CAS  Google Scholar 

  29. Mahmood T, Sarfraz RM, Akram MR, Ismail A, Qaisar MN, Shah PA (2021) Synthesis of CS-g-poly (MAA) nanogels carrier system to improve the solubility of Olmesartan Medoxomil and its in vitro evaluation. Lat Am J Pharm 40:978–990

    CAS  Google Scholar 

  30. Nesrinne S, Djamel A (2017) Synthesis, characterization and rheological behavior of pH sensitive poly (acrylamide-co-acrylic acid) hydrogels. Arab J Chem 10(4):539–547

    Article  CAS  Google Scholar 

  31. Punyamoonwongsa P, Klayya S, Sajomsang W, Kunyanee C, Aueviriyavit S (2019) Silk sericin semi-interpenetrating network hydrogels based on PEG-Diacrylate for wound healing treatment. Int J Polym Sci

  32. Zou C, Liu Y, Yan X, Qin Y, Wang M, Zhou L (2014) Synthesis of bridged β-cyclodextrin–polyethylene glycol and evaluation of its inhibition performance in oilfield wastewater. Mater Chem Phys 147(3):521–527

    Article  CAS  Google Scholar 

  33. Pal P, Singh SK, Mishra S, Pandey JP, Sen G (2019) Gum ghatti based hydrogel: Microwave synthesis, characterization, 5-Fluorouracil encapsulation and ‘in vitro’drug release evaluation. Carbohyd Polym 222:114979

    Article  CAS  Google Scholar 

  34. Hassan ZU, Bashir S, Sarfraz RM, Haroon B, Farid B, Mahmood T (2021) Comparative effectiveness of beta-cyclodextrin based copolymeric hydrogel matrices for solubility and bioavailability enhancement of lovastatin: in vitro-in vivo evaluation. LATIN Am J Pharm 40(4):822–833

    CAS  Google Scholar 

  35. Mo C-E, Chai M-H, Zhang L-P, Ran R-X, Huang Y-P, Liu Z-S (2019) Floating molecularly imprinted polymers based on liquid crystalline and polyhedral oligomeric silsesquioxanes for capecitabine sustained release. Int J Pharm 557:293–303

    Article  CAS  Google Scholar 

  36. Rana D, Bag K, Bhattacharyya SN, Mandal BM (2000) Miscibility of poly (styrene-co-butyl acrylate) with poly (ethyl methacrylate): Existence of both UCST and LCST. J Polym Sci, Part B: Polym Phys 38:369–375

    Article  CAS  Google Scholar 

  37. Rana D, Mandal BM, Bhattacharyya SN (1996) Analogue calorimetric studies of blends of poly (vinyl ester) s and polyacrylates. Macromolecules 29:1579–1583

    Article  CAS  Google Scholar 

  38. Rana D, Mandal BM, Bhattacharyya SN (1996) Analogue calorimetry of polymer blends: poly (styrene-co-acrylonitrile) and poly (phenyl acrylate) or poly (vinyl benzoate). Polymer 37:2439–2443

    Article  CAS  Google Scholar 

  39. Rana D, Mandal BM, Bhattacharyya SN (1993) Miscibility and phase diagrams of poly (phenyl acrylate) and poly (styrene-co-acrylonitrile) blends. Polymer 34:1454–1459

    Article  CAS  Google Scholar 

  40. Roy A, Maity PP, Bose A, Dhara S, Pal S (2019) β-Cyclodextrin based pH and thermo-responsive biopolymeric hydrogel as a dual drug carrier. Materials chemistry frontiers 3(3):385–393

    Article  CAS  Google Scholar 

  41. Alpizar-Reyes E, Carrillo-Navas H, Gallardo-Rivera R, Varela-Guerrero V, Alvarez-Ramirez J, Pérez-Alonso C (2017) Functional properties and physicochemical characteristics of tamarind (Tamarindus indica L.) seed mucilage powder as a novel hydrocolloid. J Food Eng 209:68–75

    Article  CAS  Google Scholar 

  42. Mahmood A, Amara Sharif FM, Sarfraz RM et al (2019) Development and in vitro evaluation of (β-cyclodextrin-g-methacrylic acid)/Na+-montmorillonite nanocomposite hydrogels for controlled delivery of lovastatin. Int J Nanomed 14:5397

    Article  CAS  Google Scholar 

  43. Sarfraz RM, Ahmad M, Mahmood A, Akram MR, Abrar A (2017) Development of β-cyclodextrin-based hydrogel microparticles for solubility enhancement of rosuvastatin: an in vitro and in vivo evaluation. Drug Des Dev Ther 11:3083

    Article  CAS  Google Scholar 

  44. Heydari A, Pardakhti A, Sheibani H (2017) Preparation and characterization of zwitterionic poly (β-cyclodextrin-co-guanidinocitrate) hydrogels for ciprofloxacin controlled release. Macromol Mater Eng 302(6):1600501

    Article  Google Scholar 

  45. Patil SB, Inamdar SZ, Reddy KR, Raghu AV, Soni SK, Kulkarni RV (2019) Novel biocompatible poly (acrylamide)-grafted-dextran hydrogels: Synthesis, characterization and biomedical applications. J Microbiol Methods 159:200–210

    Article  CAS  Google Scholar 

  46. Bartil T, Bounekhel M, Cedric C, Jérôme R (2007) Swelling behavior and release properties of pH-sensitive hydrogels based on methacrylic derivatives. Acta Pharm 57(3):301–314

    Article  CAS  Google Scholar 

  47. Xu S, Li H, Ding H et al (2019) Allylated chitosan-poly (N-isopropylacrylamide) hydrogel based on a functionalized double network for controlled drug release. Carbohyd Polym 214:8–14

    Article  CAS  Google Scholar 

  48. Krishnat K, Dhawale SC, Remeth JD, D Havaldar V, Kavitake PR (2017) Interpenetrating networks of carboxymethyl tamarind gum and chitosan for sustained delivery of aceclofenac. Marmara Pharm J 21(4):771–782

    Article  CAS  Google Scholar 

  49. Abdullah O, Usman Minhas M, Ahmad M, Ahmad S, Barkat K, Ahmad A (2018) Synthesis, optimization, and evaluation of polyvinyl alcohol-based hydrogels as controlled combinatorial drug delivery system for colon cancer. Adv Polym Technol 37(8):3348–3363

    Article  CAS  Google Scholar 

  50. Kevadiya BD, Chettiar SS, Rajkumar S et al (2014) Evaluation of Montmorillonite/Poly (L-Lactide) microcomposite spheres as ambidextrous reservoirs for controlled release of Capecitabine (Xeloda) and assessment of cell cytotoxic and oxidative stress markers. Compos Sci Technol 90:193–201

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to sincerely acknowledge the “University of Sargodha and The University of Lahore, Lahore, Pakistan” for providing instrumental support in executing the present research project.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Sargodha, Sargodha, Pakistan

    Umaira Rehman, Rai Muhammad Sarfraz, Tahir Mahmood, Nighat Batool & Bilal Haroon

  2. Department of Pharmacy, University of Chakwal, Chakwal, Pakistan

    Asif Mahmood

  3. Laboratoire de Biopharmacie Et Pharmacotechnie (LBPT), Ferhat Abbas Setif 1 University, Setif, Algeria

    Yacine Benguerba

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  1. Umaira Rehman
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Correspondence to Rai Muhammad Sarfraz.

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Rehman, U., Sarfraz, R.M., Mahmood, A. et al. Tamarind/β-CD-g-poly (MAA) pH responsive hydrogels for controlled delivery of Capecitabine: fabrication, characterization, toxicological and pharmacokinetic evaluation. J Polym Res 30, 41 (2023). https://doi.org/10.1007/s10965-022-03422-7

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