Journal
MOLECULAR PHARMACEUTICS
Volume 17, Issue 11, Pages 4256-4269Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c00675
Keywords
Curcumin; nanoparticles; hydroxypropyl-beta-cyclodextrin; antioxidant; anti-inflammation; intranasal delivery
Funding
- National University of Singapore [R-148-000180-112, R-148-000-259-112]
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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-beta-cyclodextrin-encapsulated CUR complexes (CUR/HP-beta-CD inclusion complexes) were developed and compared through intranasal administration. In vitro studies indicated that CUR in CUR/HP-beta-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-beta-CD inclusion complexes showed a higher cellular uptake level of CUR than CUR-CS-PLGA-NPs in SH-SYSY cells. Both formulations could reduce CUR's cellular cytotoxicity and showed a comparable antioxidant effect. Both formulations displayed the anti-inflammatory effect at 20 mu M CUR in BV-2 cells, which decreased TNF-alpha 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-beta-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-beta-CD inclusion complexes displayed better properties than CUR-CS-PLGA-NPs as a carrier for intranasal delivery of CUR for application in AD.
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