In Vitro and In Vivo Comparison of Curcumin-Encapsulated Chitosan-Coated Poly(lactic-co-glycolic acid) Nanoparticles and Curcumin/Hydroxypropyl-β-Cyclodextrin Inclusion Complexes Administered Intranasally as Therapeutic Strategies for Alzheimer's Disease.

Abstract

Curcumin (CUR) has antioxidant and anti-inflammatory effects that are beneficial to Alzheimer's disease (AD). However, the poor solubility and high instability of CUR compromise its application greatly. In this study, CUR-encapsulated chitosan-coated poly (lactic-co-glycolic acid) nanoparticles (CUR-CS-PLGA-NPs) and hydroxypropyl-β-cyclodextrin-encapsulated CUR complexes (CUR/HP-β-CD inclusion complexes) were developed and compared through intranasal administration. In vitro studies indicated that CUR in CUR/HP-β-CD inclusion complexes was stable under physiological conditions over 72 h with 95.41 ± 0.01% remaining, which was higher than 49.66 ± 3.91% remaining in CUR-CS-PLGA-NPs. Meanwhile, CUR/HP-β-CD inclusion complexes showed a higher cellular uptake level of CUR than CUR-CS-PLGA-NPs in SH-SY5Y cells. Both formulations could reduce CUR's cellular cytotoxicity and showed a comparable antioxidant effect. Both formulations displayed the anti-inflammatory effect at 20 μM CUR in BV-2 cells, which decreased TNF-α and IL-6 levels to approximately 70 and 40%, respectively, when compared to the positive control, respectively. In vivo pharmacokinetic studies indicated that after intranasal administration, the AUC values of CUR in the plasma and brain of the CUR/HP-β-CD inclusion complex group were 2.57-fold and 1.12-fold higher than those in the CUR-CS-PLGA-NP group at the same dose of 2 mg/kg, respectively. In conclusion, CUR/HP-β-CD inclusion complexes displayed better properties than CUR-CS-PLGA-NPs as a carrier for intranasal delivery of CUR for application in AD.

• Authors: Li Zhang, Shili Yang, Ling Rong Wong, Hui Xie, Paul Chi-Lui Ho
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 17 Issue 11 Pg. 4256-4269 (11 02 2020) ISSN: 1543-8392 [Electronic] United States
• PMID: 33084343 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Drug Carriers
• 2-Hydroxypropyl-beta-cyclodextrin
• Polylactic Acid-Polyglycolic Acid Copolymer
• Chitosan
• Curcumin

Topics

• 2-Hydroxypropyl-beta-cyclodextrin (chemistry)
• Administration, Intranasal
• Alzheimer Disease (drug therapy)
• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacokinetics)
• Antioxidants (administration & dosage, pharmacokinetics)
• Cell Line, Tumor
• Chitosan (chemistry)
• Curcumin (administration & dosage, pharmacokinetics)
• Drug Carriers (chemistry)
• Drug Compounding (methods)
• Drug Stability
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Nanoparticles (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer (chemistry)
• Solubility