title: Long-acting formulation of a new muscarinic receptor antagonist for the treatment of overactive bladder.
abstract: A new muscarinic receptor antagonist, 5-hydroxymethyl tolterodine (5-HMT), was successfully encapsulated into PLGA microspheres. With an increase of PLGA concentration from 15% to 40%, encapsulation efficiency of 5-HMT increased from 55.39% to 76.32%, and the particle size of microsphere increased from 34.33 to 70.48 µm. Increasing the homogenisation speed from 850 to 2300 rpm, the particle size was reduced about 65%.The in vitro and in vivo studies in beagle dogs show that the release profile of 5-HMT-loaded microspheres (5-HMT MS) prepared with 503H is characterised by a low initial burst followed by slow release that lasted for 2 weeks. A C(max) of 1.617 ± 0.392 ng/mL was found on the sixth day. When evaluated for inhibition of the carbachol-induced contraction of rat urinary bladder, 5-HMT MS showed a much longer and more potent effect than tolterodine tablets. The mean urination time of the rats in the 5-HMT MS group was significantly decreased (p < 0.05 or p < 0.01) to less than 2 weeks.
authors.affiliation: College of Life Science, Jilin University, Changchun, China.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
authors.forename: Chaojun
authors.initials: C
authors.lastname: Jiang
authors.forename: Fengying
authors.initials: F
authors.lastname: Sun
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.forename: Lirong
authors.initials: L
authors.lastname: Teng
authors.forename: Qingfan
authors.initials: Q
authors.lastname: Meng
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D002214:Capsules; D003408:Cresols / Q000737:chemistry / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D008863:Microspheres; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C109909:5-hydroxymethyl tolterodine; D023181:Antimicrobial Cationic Peptides; D001559:Benzhydryl Compounds; D002214:Capsules; D003408:Cresols; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C045866:peptide-Gly-Leu-amide