[Preparation of lectin-conjugated PLGA nanoparticles and evaluation of their in vitro bioadhesive activity].
In this study, wheat germ agglutinin (WGA), tomato lectin (TL) and asparagus pea lectin (AL) were covalently coupled to conventional poly lactic-co-glycolic acid (PLGA) nanoparticles using a carbodiimide method to take the bioadhesive properties. The influences of the amounts of activating agents and lectins, as well as the activating time and incubating time on the effect of lectin conjugating were investigated to optimize the preparation conditions. The mean diameters of the performed nanoparticles with or without lectin conjugation ranged from (140.7 +/- 5.7) nm to (245.6 +/- 18.3) nm. The yields of lectin conjugating and the lectin surface concentrations on nanoparticles were determined by Lowry's methods, and were calculated to be (18.97 +/- 2.9)% - (20.15 +/- 2.4)% and (9.46 +/- 1.45)--(10.05 +/- 1.19) microg x mg(-1), respectively. The in vitro bioadhesive activities of nanoparticles were evaluated by pig gastric mucin (PM) binding experiments. After incubation at room temperature for 60 min, the equilibria of binding between nanoparticles and PM reached. The percentages of the bulk PM which had interacted with different lectin-conjugated PLGA nanoparticles were 15.5%, 12.1% and 11.8%, respectively. The conjugation of lectin enhanced the interaction about 2.4 - 3.2 fold compared with that of the non-conjugated one. A mathematical model was used based on the Langmuir equation, and the rate constants of interaction (k) were calculated to be 2.373 x 10(-3), 1.536 x 10(-3) and 1.714 x 10(-3) (microg x min/mL)(-1), respectively. These interactions could be competitively inhibited by their corresponding sugars of lectins. The results suggested that lectin-conjugated PLGA nanoparticles greatly promoted the interaction with PM in vitro compared with the conventional PLGA nanoparticles, thus would improve the bioadhesion on gastrointestinal mucosa after oral administration resulting in a prolonged residence time in the gastrointestinal tract.
Yin
Ya-Shu
YS
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Chen
Da-Wei
DW
Qiao
Ming-Xi
MX
Hu
Hai-Yang
HY
Qin
Jing
J
D000268:Adhesiveness; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005752:Gastric Mucins / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles; D037121:Plant Lectins / Q000737:chemistry* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011485:Protein Binding; D014909:Wheat Germ Agglutinins / Q000737:chemistry* / Q000378:metabolism
D004337:Drug Carriers; D005752:Gastric Mucins; D037121:Plant Lectins; D014909:Wheat Germ Agglutinins; C036292:pea lectin; C034981:tomato lectin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid