IMPROVED MUCOADHESIVE PROPERTIES OF THIOLATED PECTIN FILM FOR BUCCAL DELIVERY OF DICLOFENAC

PIETRADEWI HARTRIANTI; THEODORE EBENEZER LEONARD; SHERYL LORENZO; ERIKA CHRISCENSIA; AGNES ANANIA TRIAVIKA SAHAMASTUTI

doi:10.22159/ijap.2023v15i5.48122

Authors

PIETRADEWI HARTRIANTI Department of Pharmacy, School of Life Sciences, Indonesia International Institute for Life Sciences, Jakarta 13210, Indonesia https://orcid.org/0000-0002-5315-6741
THEODORE EBENEZER LEONARD Department of Pharmacy, School of Life Sciences, Indonesia International Institute for Life Sciences, Jakarta 13210, Indonesia https://orcid.org/0000-0003-0769-8061
SHERYL LORENZO Department of Pharmacy, School of Life Sciences, Indonesia International Institute for Life Sciences, Jakarta 13210, Indonesia
ERIKA CHRISCENSIA Department of Pharmacy, School of Life Sciences, Indonesia International Institute for Life Sciences, Jakarta 13210, Indonesia https://orcid.org/0000-0002-6758-3381
AGNES ANANIA TRIAVIKA SAHAMASTUTI Department of Pharmacy, School of Life Sciences, Indonesia International Institute for Life Sciences, Jakarta 13210, Indonesia

DOI:

https://doi.org/10.22159/ijap.2023v15i5.48122

Keywords:

Buccal, Diclofenac, Mucoadhesive, Pectin, Thiolated, Buccal drug delivery

Abstract

Objective: This study was aimed to study the effect of degree of esterification (DE) on the thiolation of pectin, the potential to be used as materials for buccal delivery of diclofenac as well as the effect of DE on the physicochemical and mucoadhesive properties of the buccal films.

Methods: Low-methoxyl pectin (LMP) and high-methoxyl pectin (HMP) were synthesized into low-methoxyl thiolated pectin (LMTP) and high-methoxyl thiolated pectin (HMTP) by esterification reaction using thioglycolic acid (TGA). The degree of thiolation was evaluated using Ellman’s reaction and FT-IR. Pectins were fabricated into buccal films with diclofenac as a drug model and glycerin as the plasticizer. The obtained films were then studied for swelling and erosion percentage, mucoadhesion time, and in vitro drug release.

Results: HMTP and LMTP showed no significant difference in the degree of thiolation regardless of DE (p>0.05). The fabricated LMTP and HMTP films showed significantly higher mucoadhesion time and swelling than HMP and LMP (p<0.05). Moreover, HMTP and LMTP also exhibited sustained release of diclofenac compared to LMP (p<0.05). HMTP showed the highest mucoadhesion time, swelling capacity, and retention of drug release among all groups (p<0.05).

Conclusion: Thiolated pectin showed prospective potential to be utilized as a biopolymer for buccal delivery of diclofenac with improved mucoadhesion and controlled drug delivery, regardless of their DE.

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References

Puri V, Sharma A, Kumar P, Singh I. Thiolation of biopolymers for developing drug delivery systems with enhanced mechanical and mucoadhesive properties: a review. Polymers (Basel). 2020;12(8):1803. doi: 10.3390/polym12081803, PMID 32796741.

Leichner C, Jelkmann M, Bernkop-Schnürch A. Thiolated polymers: bioinspired polymers utilizing one of the most important bridging structures in nature. Adv Drug Deliv Rev. 2019;151-152:191-221. doi: 10.1016/j.addr.2019.04.007, PMID 31028759.

Shah KU, Shah SU, Dilawar N, Khan GM, Gibaud S. Thiomers and their potential applications in drug delivery. Expert Opin Drug Deliv. 2017;14(5):601-10. doi: 10.1080/17425247.2016.1227787, PMID 27548003.

Ahmed AB, Bhaduri I. Chemical modification, characterization and evaluation of mucoadhesive potentiality of assam bora rice starch. Int J Pharm Pharm Sci. 2017;9(9):132. doi: 10.22159/ijpps.2017v9i9.20108.

Rao MR, Gaikwad SR, Shevate PM. Synthesis and characterization of a novel mucoadhesive derivative of psyllium seed polysaccharide. Int J Pharm Pharm Sci. 2017;9(6):166. doi: 10.22159/ijpps.2017v9i6.14221.

Bandyopadhyay PK, Nayak AK. Thiolation of fenugreek seed polysaccharide; Utilization as a novel biomucoadhesive agent in drug delivery. Int J App Pharm. 2023;15(1):290-7. doi: 10.22159/ijap.2023v15i1.46459.

Tingaut P, Hauert R, Zimmermann T. Highly efficient and straightforward functionalization of cellulose films with thiol-ene click chemistry. J Mater Chem. 2011;21(40):16066. doi: 10.1039/c1jm11620g.

Jelkmann M, Bonengel S, Menzel C, Markovic S, Bernkop Schnürch A. New perspectives of starch: synthesis and in vitro assessment of novel thiolated mucoadhesive derivatives. Int J Pharm. 2018;546(1-2):70-7. doi: 10.1016/j.ijpharm.2018.05.028, PMID 29758345.

Hoang Thi TT, Lee Y, Ryu SB, Nguyen DH, Park KD. Enhanced tissue adhesiveness of injectable gelatin hydrogels through dual catalytic activity of horseradish peroxidase. Biopolymers. 2018;109(1):e23077. doi: 10.1002/bip.23077, PMID 29105737.

Xu G, Wang X, Deng C, Teng X, Suuronen EJ, Shen Z. Injectable biodegradable hybrid hydrogels based on thiolated collagen and oligo(acryloyl carbonate)–poly(ethylene glycol)–oligo(acryloyl carbonate) copolymer for functional cardiac regeneration. Acta Biomater. 2015;15:55-64. doi: 10.1016/j.actbio.2014.12.016, PMID 25545323.

Prufert F, Bonengel S, Menzel C, Bernkop Schnurch A. Enhancing the efficiency of thiomers: utilizing a highly mucoadhesive polymer as backbone for thiolation and preactivation. Eur J Pharm Sci. 2017;96:309-15. doi: 10.1016/j.ejps.2016.09.031, PMID 27702609.

Bonengel S, Hauptstein S, Leonaviciute G, Griessinger J, Bernkop-Schnürch A. Thiolated alkyl-modified carbomers: novel excipients for mucoadhesive emulsions. Eur J Pharm Sci. 2015;75:123-30. doi: 10.1016/j.ejps.2015.03.014, PMID 25857707.

Partenhauser A, Laffleur F, Rohrer J, Bernkop Schnurch A. Thiolated silicone oil: synthesis, gelling and mucoadhesive properties. Acta Biomater. 2015;16:169-77. doi: 10.1016/j.actbio.2015.01.020, PMID 25660565.

Cole MA, Bowman CN. Evaluation of thiol-ene click chemistry in functionalized polysiloxanes. J Polym Sci A Polym Chem. 2013;51(8):1749-57. doi: 10.1002/pola.26551.

Denora N, Lopedota A, Perrone M, Laquintana V, Iacobazzi RM, Milella A. Spray-dried mucoadhesives for intravesical drug delivery using N-acetylcysteine-and glutathione-glycol chitosan conjugates. Acta Biomater. 2016;43:170-84. doi: 10.1016/j.actbio.2016.07.025, PMID 27427225.

Perrone M, Lopalco A, Lopedota A, Cutrignelli A, Laquintana V, Franco M. S-preactivated thiolated glycol chitosan useful to combine mucoadhesion and drug delivery. Eur J Pharm Biopharm. 2018;132:103-11. doi: 10.1016/j.ejpb.2018.09.015, PMID 30253185.

Perera G, Barthelmes J, Bernkop Schnurch A. Novel pectin–4-amino thiophenol conjugate microparticles for colon-specific drug delivery. J Control Release. 2010;145(3):240-6. doi: 10.1016/j.jconrel.2010.04.024, PMID 20438779.

Thirawong N, Nunthanid J, Puttipipatkhachorn S, Sriamornsak P. Mucoadhesive properties of various pectins on gastrointestinal mucosa: an in vitro evaluation using texture analyzer. Eur J Pharm Biopharm. 2007;67(1):132-40. doi: 10.1016/j.ejpb.2007.01.010.

Cheewatanakornkool K, Niratisai S, Dass CR, Sriamornsak P. Redox-responsive microbeads containing thiolated pectin-doxorubicin conjugate inhibit tumor growth and metastasis: an in vitro and in vivo study. Int J Pharm. 2018;545(1-2):1-9. doi: 10.1016/j.ijpharm.2018.04.052, PMID 29702240.

Bhatia M, Ahuja M, Mehta H. Thiol derivatization of xanthan gum and its evaluation as a mucoadhesive polymer. Carbohydr Polym. 2015;131:119-24. doi: 10.1016/j.carbpol.2015.05.049, PMID 26256167.

Laffleur F, Michalek M. Modified xanthan gum for buccal delivery-a promising approach in treating sialorrhea. Int J Biol Macromol. 2017;102:1250-6. doi: 10.1016/j.ijbiomac.2017.04.123, PMID 28487193.

Geng B, Wang H, Wu S, Ru J, Tong C, Chen Y. Surface-tailored nanocellulose aerogels with thiol-functional moieties for highly efficient and selective removal of Hg(II) ions from water. ACS Sustainable Chem Eng. 2017;5(12):11715-26. doi: 10.1021/acssuschemeng.7b03188.

Arcot LR, Lundahl M, Rojas OJ, Laine J. Asymmetric cellulose nanocrystals: thiolation of reducing end groups via NHS–EDC coupling. Cellulose. 2014;21(6):4209-18. doi: 10.1007/s10570-014-0426-9.

Chattergee B, Amalina N, Sengupta P, Mandal UK. Mucoadhesive polymers and their mode of action: a recent update. J Appl Pharm Sci. 2017;7(5):195-203.

Venzon SS, Canteri MHG, Granato D, Junior BD, Maciel GM, Stafussa AP. Physicochemical properties of modified citrus pectins extracted from orange pomace. J Food Sci Technol. 2015;52(7):4102-12. doi: 10.1007/s13197-014-1419-2, PMID 26139875.

Sharma R, Ahuja M. Thiolated pectin: synthesis, characterization and evaluation as a mucoadhesive polymer. Carbohydr Polym. 2011;85(3):658-63. doi: 10.1016/j.carbpol.2011.03.034.

Hauptstein S, Hintzen F, Muller C, Ohm M, Bernkop Schnurch A. Development and in vitro evaluation of a buccal drug delivery system based on preactivated thiolated pectin. Drug Dev Ind Pharm. 2014;40(11):1530-7. doi: 10.3109/03639045.2013.836213, PMID 24025071.

Iswandana R, Putri KSS, Sandiata CE, Triani S, Sari SP, Djajadisastra J. Formulation of tetrandrine beads using ionic gelation method Ca-pectinate coated pH-sensitive polymers as the colon-targeted dosage form. Asian J Pharm Clin Res. 2017;10(10):90. doi: 10.22159/ajpcr.2017.v10i10.19994.

Fracasso AF, Perussello CA, Carpine D, Petkowicz CLO, Haminiuk CWI. Chemical modification of citrus pectin: structural, physical and rheologial implications. Int J Biol Macromol. 2018;109:784-92. doi: 10.1016/j.ijbiomac.2017.11.060, PMID 29133098.

Laffleur F. Mucoadhesive polymers for buccal drug delivery. Drug Dev Ind Pharm. 2014;40(5):591-8. doi: 10.3109/03639045.2014.892959, PMID 24576266.

Hinz B, Chevts J, Renner B, Wuttke H, Rau T, Schmidt A. Bioavailability of diclofenac potassium at low doses. Br J Clin Pharmacol. 2005;59(1):80-4. doi: 10.1111/j.1365-2125.2005.02226.x, PMID 15606444.

Bernkop Schnurch A, Hornof M, Zoidl T. Thiolated polymers–thiomers: synthesis and in vitro evaluation of chitosan-2-iminothiolane conjugates. Int J Pharm. 2003;260(2):229-37. doi: 10.1016/s0378-5173(03)00271-0, PMID 12842342.

Hartrianti P, Nguyen LTH, Johanes J, Chou SM, Zhu P, Tan NS. Fabrication and characterization of a novel crosslinked human keratin-alginate sponge. J Tissue Eng Regen Med. 2017;11(9):2590-602. doi: 10.1002/term.2159, PMID 27109145.

Fleming I, Williams D. Spectroscopic methods in organic chemistry. 7th ed. Berlin: Springer; 2019. p. 88-121.

Fernandes FP, Fortes AC, da Cruz Fonseca SG, Breitkreutz J, Ferraz HG. Manufacture and characterization of mucoadhesive buccal films based on pectin and gellan gum containing triamcinolone acetonide. Int J Polym Sci. 2018;2018:1-10. doi: 10.1155/2018/2403802.

Junmahasathien T, Panraksa P, Protiarn P, Hormdee D, Noisombut R, Kantrong N. Preparation and evaluation of metronidazole-loaded pectin films for potentially targeting a microbial infection associated with periodontal disease. Polymers (Basel). 2018;10(9):1021. doi: 10.3390/polym10091021, PMID 30960947.

Leonard TE, Liko AF, Gustiananda M, Putra ABN, Juanssilfero AB, Hartrianti P. Thiolated pectin-chitosan composites: potential mucoadhesive drug delivery system with selective cytotoxicity towards colorectal cancer. Int J Biol Macromol. 2023;225:1-12. doi: 10.1016/j.ijbiomac.2022.12.012, PMID 36481327.

Shahiwala A, Misra A. Applications of polymers in drug delivery. 2nd ed. UK: Smithers Rapra Technology Ltd; 2014. p. 59-81.