ABSTRACT
Polyelectrolyte layer-by-layer assembled lipid nanoparticles (NPs) were prepared to improve their stability against lipolysis in gastrointestinal tract, and efficiency of oral absorption of doxorubicin (DOX). The lipid NPs were prepared by hot melt-probe sonication method. The polyelectrolyte layer-by-layer assembled lipid NPs (DOX-NPs/CS/γ-PGA) was prepared by layer-by-layer self-assembling polyelectrolytes cationic chitosan (CS) and anionic poly (γ-glutamic acid) (γ-PGA) on the surface of lipid NPs based on electrostatic interaction. The particle size, polydispersity index (PDI) and zeta potential of lipid NPs and DOX-NPs/CS/γ-PGA were determined by dynamic light scattering (DLS). The in vitro drug release was determined in pH 1.2 HCl solution and pH 6.8 phosphate buffer solution (PBS). The stability of lipid NPs against lipolysis was evaluated in simulated gastrointestinal medium containing lipase. The cellular uptake of lipid NPs and DOX-NPs/CS/γ-PGA was evaluated in Caco-2 cell model. The pharmacokinetic of DOX after oral absorption was studied in SD rats. Results showed that the average particle size and zeta potential of DOX-NPs/CS/γ-PGA were 180.6±5.4 nm and -38.53±0.29 mV, respectively. The DOX-NPs/CS/γ-PGA effectively slowed down the release of DOX from nanoparticles, and decreased the lipolysis of lipid NPs in simulated gastrointestinal medium. The cell study showed that DOX-loaded lipid NPs and DOX-NPs/CS/γ-PGA remarkably enhanced the cell uptake in comparison with DOX solution. The DOX-NPs/CS/γ-PGA significantly improved oral absorption of DOX compared with DOX-loaded lipid NPs. The Cmax, tmax were 0.76±0.25 μg·mL-1 and 0.5 h, respectively; AUC0-24h was 3.02 folds and the relative bioavailability was 302.46% with DOX solution as reference. The stability of lipid NPs against lipolysis and drug release were significantly improved by layer-by-layer assembling, leading to an improved oral absorption.
ABSTRACT
?AlM: To evaluate the long - term effects of laser peripheral iridectomy ( LPl ) and trabeculectomy in treating early chronic angle-closure glaucoma. ?METHODS: Ninety-eight patients (102 eyes) with early chronic primary angle-closure glaucoma were randomly divided into two groups. Group A of 50 patients (54 eyes) was treated with LPl and group B of 48 patients (48 eyes) with trabeculectomy. After 3 - 8y of follow - up observation, comparison would be made from the perspectives of postoperative eyesight, intraocular pressure, anterior chamber angle, visual field and cup/disc ratio ( C/D) . ?RESULTS:ln group A, 24 eyes with eyesight declining, 22 eyes with theintraocular pressure>21mmHg (1mmHg=0. 133kPa), 21 eyes with chamber angle synechia >180o, 21 eyes with visual field narrowed, 21 eyes with C/D ratio enlarged. The results of group B for the same items were 10, 5, 4, 4, 4 eyes respectively. The comparative difference was statistically significant (P ?CONCLUSlON:Good effects will be achieved for early-stage chronic angle - closure glaucoma with surgical method. Trabeculectomy is obviously better than LPl for the long-term effects.