title: Solanum tuberosum lectin-conjugated PLGA nanoparticles for nose-to-brain delivery: in vivo and in vitro evaluations.
abstract: Solanum tuberosum lectin (STL) conjugated poly (DL-lactic-co- glycolic acid) (PLGA) nanoparticle (STL-NP) was constructed in this paper as a novel biodegradable nose-to-brain drug delivery system. The in vitro uptake study showed markedly enhanced endocytosis of STL-NP compared to unmodified PLGA nanoparticles (NP) in Calu-3 cells and significant inhibition of uptake in the presence of inhibitor sugar (chitin hydrolysate). Following intranasal administration, coumarin-6 carried by STL-NP was rapidly absorbed into blood and brain. The AUC((0→12 h)) of coumarin-6 in blood, olfactory bulb, cerebrum and cerebellum were about 0.77-, 1.48-, 1.89- and 1.45-fold of those of NP, respectively (p < 0.05). STL-NP demonstrated 1.89-2.45 times (p < 0.01) higher brain targeting efficiency in different brain tissues than unmodified NP. Enhanced accumulation of STL-NP in the brain was also observed by near infrared fluorescence probe image following intranasal administration. The fluorescence signal of STL-NP appeared in olfactory bulb, cerebrum and brainstem early at 0.25 h. The signal in olfactory bulb decreased gradually after 2 h, while the obvious signal in brainstem, cerebrum and cerebellum lasted for more than 8 h. The STL-NP safety experiments showed mild cytotoxicity and negligible cilia irritation. These intriguing in vitro and in vivo results suggest that STL-NP might serve as a promising brain drug delivery system.
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors: Jie
authors: J
authors: Chen
authors: Chi
authors: C
authors: Zhang
authors: Qingfeng
authors: Q
authors: Liu
authors: Xiayan
authors: X
authors: Shao
authors: Chengcheng
authors: C
authors: Feng
authors: Yehong
authors: Y
authors: Shen
authors: Qizhi
authors: Q
authors: Zhang
authors: Xinguo
authors: X
authors: Jiang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001001:Anura; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002686:Chitin / Q000737:chemistry / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D010316:Particle Size; D037121:Plant Lectins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003374:Coumarins; D007093:Imidazoles; D037121:Plant Lectins; D013844:Thiazoles; C517282:coumarin 6; C517283:coumarin 7; C041202:potato lectin; D002686:Chitin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid