A comparative study on the efficiency of chitosan-N-acetylcysteine, chitosan oligosaccharides or carboxymethyl chitosan surface modified nanostructured lipid carrier for ophthalmic delivery of curcumin.
To develop a potential nanocarrier for the topical ocular administration of curcumin (CUR), a novel thiolated chitosan was synthesized by the covalent binding between N-acetyl-l-cysteine (NAC) and chitosan (CS) to surface modify the nanostructured lipid carrier loaded CUR (CUR-NLC). And the superiorities of the CS-NAC co polymer coated CUR-NLC over chitosan oligosaccharides (COS) or carboxymethyl chitosan (CMCS) modification were also verified in detail. As expected, the increment in particle size and the reversal of zeta potential occurred after surface decorating, and the most prominent electropositivity was obtained for the CS-NAC-CUR-NLC group. Additionally, the utilization of the CS-NAC coating demonstrated an effectively controlled release over 72h and attained a 6.4 and 18.8 fold increase in apparent permeability coefficients (Papp) compared with the CUR-NLC and the self-made eye drops, respectively. Meanwhile, the clearance rate of the NLC labeled with Rhodamine B was significantly delayed in the presence of CS-NAC. By contrast, CS-NAC-CUR-NLC was superior to the COS and CMCS coated ones in view of in vitro release, drug permeability and corneal retention. Moreover, the results of the in-vivo and in-vitro characteristics demonstrated that the promoting effect of CMCS coating was relatively weaker than COS coated ones. Ocular irritation test was executed on the CS-NAC-CUR-NLC, neither a sign of toxicity nor irritation to the external ocular tissues was observed. In conclusion, CS-NAC-CUR-NLC possesses a greater potential as an ocular drug-delivery system comparing with the COS-CUR-NLC and CMCS-CUR-NLC.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Jinyu
J
Li
School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China. Electronic address: liudandan1124@126.com.
Dandan
D
Liu
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Guoxin
G
Tan
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Zhinan
Z
Zhao
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Xinggang
X
Yang
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: pppwwwsss@163.com.
Weisan
W
Pan
D000111:Acetylcysteine / Q000737:chemistry; D060433:Administration, Ophthalmic; D000818:Animals; D002686:Chitin / Q000031:analogs & derivatives / Q000737:chemistry; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D007700:Kinetics; D008055:Lipids; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D009844:Oligosaccharides; D010316:Particle Size; D010539:Permeability; D011817:Rabbits
D004337:Drug Carriers; D008055:Lipids; D009844:Oligosaccharides; C514968:carboxymethyl-chitosan; C540141:chitosan-N-acetylcysteine conjugate; C493484:oligochitosan; D002686:Chitin; D048271:Chitosan; D003474:Curcumin; D000111:Acetylcysteine
Carboxymethyl chitosan; Chitosan oligosaccharides; Chitosan-N-acetyl-l-cysteine; Curcumin; Nanostructured lipid carrier; Ophthalmic drug delivery