title: Development and evaluation of PEGylated Enoxaparin: a novel approach for enhanced anti-Xa activity.
abstract: Enoxaparin (ENX) is one of the most widely prescribed low molecular weight heparin inprophylaxis and treatment of venous thromboembolism. In this study, Enoxaparin-PEG conjugate (P-ENX) was synthesized from Enoxaparin and polyethylene glycol (PEG) and evaluated for its potential for extended duration of action. The esterification of the carboxyl groups of the drug moiety with the hydroxyl groups of mPEG-2000 was done by employing carbodiimide coupling chemistry. P-ENX conjugate was purified by dialysis and characterized by Fourier transform infrared spectroscopy (FTIR), Proton-Nuclear magnetic resonance ((1)H NMR) and matrix-assisted laser desorption/ionization (MALDI) mass analysis techniques. FTIR analysis revealed frequency of the carbonyl group in accord with ester linkage formation between the drug and the PEG moiety. (1)H NMR of the conjugate showed significant change in the chemical shift further indicative of ENX and PEG chemical interaction. In MALDI spectra, small peaks at 12,907 and 16,137 m/z confirmed the probability of conjugation of ENX and PEG. P-ENX exhibited considerable enhancement in anti-Xa activity (by three-folds) in comparison to free ENX. Further, an increase in AUC (over four-folds) was observed in P-ENX. Thus, PEGylation of ENX is a novel approach for extended and enhanced activity of ENX with a potential for decreased dosing frequency.
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160067, India.
authors.forename: Anupam Kumar
authors.initials: AK
authors.lastname: Choubey
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160067, India.
authors.forename: Chander Parkash
authors.initials: CP
authors.lastname: Dora
authors.affiliation: Technology Development Centre, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160067, India.
authors.forename: Tara Dutt
authors.initials: TD
authors.lastname: Bhatt
authors.affiliation: Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160067, India.
authors.forename: Manjinder Singh
authors.initials: MS
authors.lastname: Gill
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160067, India. Electronic address: ssuresh@niper.ac.in.
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000818:Animals; D017984:Enoxaparin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015951:Factor Xa / Q000378:metabolism*; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D015394:Molecular Structure; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011092:Polyethylene Glycols; D015951:Factor Xa
keywords: Anti-Xa activity; Enoxaparin; Low molecular weight heparin; Polyethylene glycol conjugate; Venous thromboembolism