Study on the Absorption of Silymarin Enteric Coated-PLGA Nanoparticles in Rat in situ Intestine Perfu-sion Model and Caco-2 Cell Model / 中国药房

OBJECTIVE:To study the absorption features of Silymarin enteric coated-polyllactic-co-glycolic acid (PLGA) nanoparticles in rat in situ intestine perfusion model and colonic adenoma Caco-2 cell model. METHODS:HPLC method was used to determine the content of silymarin. The absorption rate constant(Ka)and apparent absorption coefficient(Kapp)of Silymarin sus-pension,Silymarin PLGA nanoparticles and Silymarin enteric coated-PLGA nanoparticles were investigated in duodenum,jejunum, ileum and colon of rat in situ intestine perfusion model;the apparent permeability coefficient (Papp) of those drugs containing low-concentration,medium-concentration and high-concentration(20,40,60 μg/mL)of silymarin in Caco-2 cell model were also investigated. RESULTS:Compared with Silymarin suspension,Ka and Kapp of Silymarin PLGA nanoparticles and Silymarin enteric coated-PLGA nanoparticles were all increased in duodenum,jejunum,ileum and colon(P0.05). CONCLUSIONS:Silymarin enteric coated-PLGA nanoparticles can effectively increase the intestinal ab-sorption,cellular uptake and transmembrane transport rate of silymarin.

Preparation, characteristic and in vivo study of H102 loaded PEG-PLGA nanoparticles / 中国药学杂志

OBJECTIVE: To prepare H102 loaded PEG-PLGA nanoparticles (H102-NP) and investigate its properties in vitro and in vivo. METHODS: Orthogonal design was used to optimize the formulation. The nanoparticles were characterized in terms of morphology, size, Zeta potential, drug encapsulation efficiency, in vitro release and stability. H102 concentrations in plasma and brain following tail vein injection of H102-NP in mice were measured by LC-MS. RESULTS: H102-NP were spherical and of regular size. The average size, Zeta potential and encapsulation efficiency of H102-NP were found to be around 137 nm, -38 mV and 64%. The cumulative release of H102-NP in pH 7.4 PBS and plasma at 12 d is 93% and 95%, respectively. Incubated in plasma and brain homogenate at 37°C for 12 h, the degradation of H102 encapsulated in nanoparticles was only 5%. Compared with H102 solution which was eliminated rapidly in blood with low concentration in brain, H102-NP was eliminated slowly in blood with higher concentration and longer duration in brain after intravenous administered in mice. The AUC of H102-NP was 245 times and 11 times higher in plasma and brain than that of H102 solution. CONCLUSION: H102-loaded nanoparticles are successfully prepared with good properties in vitro and in vivo, which showed a prospect for the treatment of Alzheimer's disease.

Preparation of transferrin and RGD co-modified PLGA nanoparticles and its targeting to melanoma / 中国生化药物杂志

Objective To prepare transferrin and Arg-Gly-Asp polypeptide co-modified nanoparticles(TF/RGD-NPs)and evaluate its targeting efficiency to melanoma.Methods The co-modified nanoparticles were prepared by emulsion method and its appearance,particle size and Zeta potential were evaluated.The cellular uptake experiment and melanoma tumor spheroids penetration test were used to evaluate the affinity and ability to penetrate tumor tissues of TF/RGD-NPs to melanoma B16 cells. Results The particle diameter of co-modified nanoparticles was(113.4 ±12.5)nm and the Zeta potential was(4.53 ±2.15)mV.In vitro uptake test demonstrated that the efficacy of cellular uptaken TF/RGD-NPs by B16 cells were 2.7 times and 2.9 times to TF-NPs and RGD-NPs,respectively,the differences were all significant(P<0.05 ).Tumor spheroid penetration test results showed that TF/RGD-NPs has good affinity to melanoma cells.Conclusion TF/RGD-NPs can target to melanoma B16 cell efficiency in vitro,it may be serve as a potential drug delivery system for targeting melanoma.

Transport route of fluorescent probe via inner ear administration / 中国药学杂志

OBJECTIVE: To investigate transport route of fluorescent probe following inner ear administration. METHODS: Coumarin-6 (CM) was employed as fluorescent probe and CM-loaded poly (lactic-co-glycolic acid) nanoparticles (CM-PLGA-NP) were prepared by emulsification-solvent evaporation method. Perilymph (PL), contralateral PL, cerebrospinal fluid (CSF) and plasma were collected periodically in guinea pigs after unilateral intratympanic administration of CM-PLGA-NP or CM solution. The concentrations of CM were determined by high performance liquid chromatography (HPLC), and statistic program DAS was applied to the calculation of pharmacokinetic parameters. RESULTS: CM was found in PL, contralateral PL and CSF after unilateral intratympanic administration of CM-PLGA-NP or CM solution. The AUC in PL and CSF following intratympanic administration of CM-PLGA-NP were respectively 3.7 and 7.6-fold higher than those following intratympanic administration of CM solution. And the ρmax in PL and CSF were respectively 9.9 and 9.0-fold higher. Moreover, CM-PLGA-NP extended the MRT in PL and CSF by 5.1 and 9.4 times compared with CM solution. CONCLUSION: Transport pathway of intra-cochlear administration is PL → CSF → contralateral PL. Nanoparticles can greatly improve drug distribution within the inner ear and CSF, and prolong the residence time. Copyright 2012 by the Chinese Pharmaceutical Association.