title: Development and Evaluation of Diclofenac Sodium Loaded-N-Trimethyl Chitosan Nanoparticles for Ophthalmic Use.
abstract: The ophthalmic preparation of diclofenac sodium (DC) for relieving ocular inflammation is presently available in the market only as an eye drop solution. Due to its low occular bioavailability, it requires frequent application leading to low patients' compliance and quality of life. This study was conducted to develop formulations of DC loaded-N-trimethyl chitosan nanoparticles (DC-TMCNs) for ophthalmic use to improve ocular biavailabiltiy of DC. DC-TMCNs varied in formulation compositions were prepared using ionic gelation technique and evaluated for their physicochemical properties, drug release, eye irritation potential, and ophthalmic absorption of diclofenac sodium. N-Trimethyl chitosan (TMC) with a 49.8% degree of quaternization was synthesized and used for DC-TMCNs production. The obtained DC-TMCNs had particle size in a range of 130-190 nm with zeta potential values of +4 to +9 mV and drug entrapment efficiencies of more than 70% depending on the content of TMC and sodium tripolyphosphate (TPP). The optimized DC-TMCNs formulation contained TMC, DC, and TPP at a weight ratio of TMC/DC/TPP = 3:1:1. Their lyophilized product reconstituted with phosphate buffer solution pH 5.5 possessed a drug release pattern that fitted within the zero-order model. The eye irritation tests showed that DC-TMCNs were safe for ophthalmic use. The in vivo ophthalmic drug absorption study performed on rabbits indicated that DC-TMCNs could improve ophthalmic bioavailability of DC. Results of this study suggested that DC-TMCNs had potential for use as an alternative to conventional DC eye drops for ophthalmic inflammation treatment.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Pathumthani, 12120, Thailand. rathapona@hotmail.com.
authors.forename: Rathapon
authors.initials: R
authors.lastname: Asasutjarit
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Rangsit University, Pathumthani, 12000, Thailand.
authors.forename: Thitaree
authors.initials: T
authors.lastname: Theerachayanan
authors.affiliation: Group of Research and Development, Thailand Institute of Nuclear Technology (Public Organization), Nakhonnayok, 26120, Thailand.
authors.forename: Prartana
authors.initials: P
authors.lastname: Kewsuwan
authors.affiliation: National Center For Genetic Engineering and Biotechnology, National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani, 12120, Thailand.
authors.forename: Sukitaya
authors.initials: S
authors.lastname: Veeranodha
authors.affiliation: National Metal and Materials Technology Center, National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani, 12120, Thailand.
authors.forename: Asira
authors.initials: A
authors.lastname: Fuongfuchat
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Garnpimol C
authors.initials: GC
authors.lastname: Ritthidej
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry* / Q000633:toxicity; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles; D065587:Ocular Absorption; D009883:Ophthalmic Solutions; D010316:Particle Size; D011122:Polyphosphates / Q000737:chemistry; D011817:Rabbits; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; C118071:N-trimethyl chitosan chloride; D009883:Ophthalmic Solutions; D011122:Polyphosphates; D004008:Diclofenac; D048271:Chitosan; C005692:triphosphoric acid
keywords: N-trimethyl chitosan nanoparticles; diclofenac sodium; ophthalmic drug absorption; ophthalmic drug delivery; physicochemical properties