title: Mucoadhesive polyacrylamide nanogel as a potential hydrophobic drug carrier for intravesical bladder cancer therapy.
abstract: In this paper, amine-functionalized polyacrylamide nanogels (PAm-NH2) loaded with docetaxel (DTX) were evaluated as a mucoadhesive and sustained intravesical drug delivery (IDD) system for potential bladder cancer therapy. Nanogels have not been applied for such therapy before. The mucoadhesiveness of the PAm-NH2 nanogels, which is a critical factor for IDD application, was investigated using the mucin-particle method and by analyzing the direct attachment of the PAm-NH2 nanogels onto the luminal surface of porcine urinary bladder. DTX, as a model hydrophobic drug, was successfully loaded into hydrophilic PAm-NH2 nanogels with high loading efficiency (>90%), and sustained release of DTX from the nanogels over 9 days in artificial urine was achieved. The nanogels were also taken in by bladder cancer cells in a concentration-dependent manner. The efficiency of the DTX-loaded nanogels in killing UMUC3 and T24 bladder cancer cells was determined to be equivalent to free DTX, and the morphology of the bladder urothelium was not adversely altered by the PAm-NH2 nanogels. These findings indicate that such mucoadhesive nanogels are potentially a promising candidate for intravesical delivery of hydrophobic drugs in bladder cancer therapy.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 117576, Singapore.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 117576, Singapore. Electronic address: chenkg@nus.edu.sg.
authors.forename: Koon Gee
authors.initials: KG
authors.lastname: Neoh
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 117576, Singapore.
authors.forename: En-Tang
authors.initials: ET
authors.lastname: Kang
authors.affiliation: Department of Surgery, National University of Singapore, Kent Ridge, Singapore 117576, Singapore.
authors.forename: Ratha
authors.initials: R
authors.lastname: Mahendran
authors.affiliation: Department of Surgery, National University of Singapore, Kent Ridge, Singapore 117576, Singapore.
authors.forename: Edmund
authors.initials: E
authors.lastname: Chiong
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage* / Q000737:chemistry; D000268:Adhesiveness; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D005782:Gels; D057927:Hydrophobic and Hydrophilic Interactions; D009077:Mucins / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D013552:Swine; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; D000077143:Docetaxel; D004337:Drug Carriers; D005782:Gels; D009077:Mucins; D043823:Taxoids; D000099166:Polyacrylamides
keywords: Bladder cancer; Hydrophobic drug; Intravesical drug delivery; Mucoadhesive; Nanogels