title: Potential advantages of a novel chitosan-N-acetylcysteine surface modified nanostructured lipid carrier on the performance of ophthalmic delivery of curcumin.
abstract: The transient precorneal retention time and low penetration capacity into intraocular tissues are the key obstacles that hinder the ophthalmic drug delivery of many therapeutic compounds, especially for drugs with poor solubility and permeability. To break the stalemate, N-acetyl-L-cysteine functionalized chitosan copolymer (CS-NAC), which exhibit marked bioadhesion and permeation enhancing effect, was synthesized. The curcumin encapsulated NLC (CUR-NLC) was produced and optimized followed by surface absorption of CS-NAC. After coating, changed particle size from 50.76 ± 2.21 nm to 88.64 ± 1.25 nm and reversed zeta potential from -20.38 ± 0.39 mV to 22.51 ± 0.34 mV was observed. The in vitro CUR release from NLC was slower than that of CUR-NLC and chitosan hydrochlorides (CH) coated NLC due to the inter and/or intramolecular disulfide formation of thiomers on the surface of nanocarriers. The modification also significantly enhanced transcorneal penetration compared with CH-NLC and the uncoated ones. The effect on bioadhesion and precorneal retention were evaluated by in vivo imaging technique and ocular pharmacokinetics studies revealing that the clearance of the formulations was significantly delayed in the presence of CS-NAC and the effect was positively related to the degree of thiolation. In summary, CS-NAC-NLC presented a series of notable advantages for ophthalmic drug application.
authors.affiliation: School of Biomedical &Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Queen's University Belfast, University Road, Belfast BT7 1NN, Northern Ireland, UK.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: School of Biomedical &Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
authors.forename: Fengwei
authors.initials: F
authors.lastname: He
authors.affiliation: Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin 300193, PR China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Biomedical &Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
authors.forename: Qingyin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Biomedical &Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Bai
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D003315:Cornea / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D011817:Rabbits; D013499:Surface Properties
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D008055:Lipids; D009883:Ophthalmic Solutions; C540141:chitosan-N-acetylcysteine conjugate; D048271:Chitosan; D003474:Curcumin; D000111:Acetylcysteine