PLGA nanoparticles for the oral delivery of nuciferine: preparation, physicochemical characterization and in vitro/in vivo studies.
This article reports a promising approach to enhance the oral delivery of nuciferine (NUC), improve its aqueous solubility and bioavailability, and allow its controlled release as well as inhibiting lipid accumulation. NUC-loaded poly lactic-co-glycolic acid nanoparticles (NUC-PLGA-NPs) were prepared according to a solid/oil/water (s/o/w) emulsion technique due to the water-insolubility of NUC. PLGA exhibited excellent loading capacity for NUC with adjustable dosing ratios. The drug loading and encapsulation efficiency of optimized formulation were 8.89 ± 0.71 and 88.54 ± 7.08%, respectively. NUC-PLGA-NPs exhibited a spherical morphology with average size of 150.83 ± 5.72 nm and negative charge of -22.73 ± 1.63 mV, which are suitable for oral administration. A sustained NUC released from NUC-PLGA-NPs with an initial exponential release owing to the surface associated drug followed by a slower release of NUC, which was entrapped in the core. In addition, ∼77 ± 6.67% was released in simulating intestinal juice, while only about 45.95 ± 5.2% in simulating gastric juice. NUC-PLGA-NPs are more efficient against oleic acid (OA)-induced hepatic steatosis in HepG2cells when compared to naked NUC (n-NUC, *p < 0.05). The oral bioavailability of NUC-PLGA-NPs group was significantly higher (**p < 0.01) and a significantly decreased serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as a higher concentration of high-density lipoprotein cholesterol (HDL-C) was observed, compared with that of n-NUC treated group. These findings suggest that NUC-PLGA-NPs hold great promise for sustained and controlled drug delivery with improved bioavailability to alleviating lipogenesis.
a Department of Clinical Pharmacy.
Ying
Y
Liu
a Department of Clinical Pharmacy.
Xin
X
Wu
b Department of General Surgery , and.
Yushuai
Y
Mi
c Department of Acupuncture and Moxibustion, Shanghai General Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , PR China.
Bimeng
B
Zhang
a Department of Clinical Pharmacy.
Shengying
S
Gu
a Department of Clinical Pharmacy.
Gaolin
G
Liu
a Department of Clinical Pharmacy.
Xiaoyu
X
Li
D000284:Administration, Oral; D000818:Animals; D001060:Aporphines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D055598:Chemical Phenomena; D016503:Drug Delivery Systems / Q000379:methods*; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D001060:Aporphines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C008692:nuciferine
Nuciferine; PLGA; bioavailability; lipid lowering; nanoparticles