title: Adhesion of thiolated silica nanoparticles to urinary bladder mucosa: Effects of PEGylation, thiol content and particle size.
abstract: Intravesical drug administration is used to deliver cytotoxic agents through a catheter to treat bladder cancer. One major limitation of this approach is poor retention of the drug in the bladder due to periodic urine voiding. Mucoadhesive dosage forms thus offer significant potential to improve drug retention in the bladder. Here, we investigate thiolated silica nanoparticles retention on porcine bladder mucosa in vitro, quantified through Wash Out50 (WO50) values, defined as the volume of liquid necessary to remove 50% of the adhered particles from a mucosal tissue. Following irrigation with artificial urine solution, the thiolated nanoparticles demonstrate significantly greater retention (WO50 up to 36mL) compared to non-mucoadhesive dextran (WO50 7mL), but have weaker mucoadhesive properties than chitosan (WO50 89mL). PEGylation of thiolated silica reduces their mucoadhesion with WO50 values of 29 and 8mL for particles decorated with 750 and 5000Da PEG, respectively. The retention of thiolated silica nanoparticles is dependent on their thiol group contents and physical dimensions.
authors.affiliation: Reading School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AD, United Kingdom.
authors.forename: Ellina A
authors.initials: EA
authors.lastname: Mun
authors.affiliation: Reading School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AD, United Kingdom.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Williams
authors.affiliation: Reading School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AD, United Kingdom. Electronic address: v.khutoryanskiy@reading.ac.uk.
authors.forename: Vitaliy V
authors.initials: VV
authors.lastname: Khutoryanskiy
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001682:Biological Availability; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D009092:Mucous Membrane / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D013552:Swine; D001743:Urinary Bladder / Q000378:metabolism*
chemical_list: D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D048271:Chitosan
keywords: Intravesical drug delivery; Mucoadhesion; PEGylation; Silica nanoparticles; Thiomers; Urinary bladder; Wash Out(50) (WO(50))