title: Microwave-assisted facile synthesis of a new tri-block chitosan conjugate with improved mucoadhesion.
abstract: A new chitosan-based tri-block conjugate, O-PEG-chitosan-N-cysteine was synthesized using microwave irradiation. For synthesis of this derivative, chitosan was modified to a PEG-chitosan conjugate followed by PEG-chitosan-cysteine using 6-O PEGylation and 2-N-thiolation, respectively. The synthesized derivative was characterized using various analytical techniques such as FT-IR and (1)H NMR spectroscopy. The conjugate was also analyzed for its biochemical, biodegradation and mucoadhesive properties. The modified chitosan conjugate exhibited improved mucoadhesion behavior (14.0 h) with greater biodegradation compared to the parent polymer (6.3h). The in silico modeling corroborated with the in vitro study demonstrating a stable complex between mucin and O-PEG-chitosan-N-cysteine conjugate (ΔE=-60.100 kcal/mol) compared to mucin and chitosan conjugate. The synthesis proposed herein, involves the use of microwave irradiation which causes a substantial reduction in the reaction time (approximately 2.30 h) compared to conventional method (35 h).
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa; Pharmaceutical Chemistry Department, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Sant Tukaram Nagar, Pimpri, Pune, Maharashtra 411018, India.
authors.forename: Ravindra V
authors.initials: RV
authors.lastname: Badhe
authors.affiliation: Pharmaceutical Chemistry Department, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Sant Tukaram Nagar, Pimpri, Pune, Maharashtra 411018, India.
authors.forename: Rabindra K
authors.initials: RK
authors.lastname: Nanda
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.
authors.forename: Dharmesh R
authors.initials: DR
authors.lastname: Chejara
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.affiliation: Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa. Electronic address: viness.pillay@wits.ac.za.
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001672:Biocompatible Materials; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000737:chemistry*; D008872:Microwaves; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013552:Swine
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D011092:Polyethylene Glycols; D048271:Chitosan
keywords: Chitosan; In silico modeling; Microwave; Mucoadhesion; PEGylation; Thiolation