ABSTRACT
Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-K(s-s)R8-An micelles maintained a reasonable size (80-160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency , improved uptake in glioma cells and good biocompatibility and . In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells . Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.
ABSTRACT
OBJECTIVE@#: To analyze experimental factors affecting recovery of puerarin in microdialysis.@*METHODS@#: Puerarin concentration in microdialysate samples was determined by high performance liquid chromatography. The methods of direct dialysis, retrodialysis and the zero-net flux were used to calculate recovery, respectively. The effects of perfusate composition, the analyte concentration, perfusate flow rate, medium temperature and stir rates of the dialysis medium on recovery were investigated.@*RESULTS@#: There were significant differences in the recovery values among direct dialysis, retrodialysis and zero-net flux methods. The recovery for 0.9% NaCl solution, Ringer's solution, PBS and anticoagulant dextrose solution as perfusate fluid were (71.25±2.36)%,(73.48±1.41)%,(68.50±2.43)% and (74.98±1.16)%, respectively. The composition of perfusate fluid had significant influence on the recovery(<0.01). At the same flow rate, recovery was independent of the analyte concentration. At the same concentration, the recovery was decrease with the increasing flow rate in an exponential relationship. The recovery increased with the raising temperature and stir rate of the dialysis medium, and the recovery remained stable when the stir rate reached above 200 rpm.@*CONCLUSIONS@#: A study method for recovery of puerarin in microdialysis has been established, and the recovery of puerarin is affected by calculating methods, perfusate fluids, flow rate, medium temperature and stir rate, but not affected by analyte concentrations.
Subject(s)
Chemistry Techniques, Analytical , Methods , Chromatography, High Pressure Liquid , Isoflavones , MicrodialysisABSTRACT
Objective To prepare a novel drug delivery system camptothecin loaded nanogel (CPT-PPO gel),and inves-tigate its contents,physical and chemical properties and in vitro transdermal permeability.Methods The solvent evaporation method was utilized to prepare core-shell nano-drug delivery systems (CPT-PLGA-PAMAM,CPT-PP),in which the Poly lac-tic-co-glycolic acid (PLGA ) was used to load camptothecin as the nucleus and the polyamidoamine (PAMAM ) G3.0 was wrapped in the surface of PLGA as the shell.Then the oleic acid (OA) was connected to CPT-PP to obtain the surface modified drug delivery system (CPT-PLGA-PAMAM OA,CPT-PPO).HPLC was used to determine the content of camptothecin in nanoparticles,transmission electron microscopy was applied to identify the nanoparticles morphology,and laser analyzer was used to determine the particle size.The hydroxypropyl methylcellulose (HPMC) was added as the base for the preparation of the nanogel (CPT-PPO gel) at last.The Franz-diffusion cell was used to determine the permeation rate of nanogel in vitro. Results The resulting CPT-PPO gel was stable at 4℃,the average particle size was (246.7 ± 5.4) nm and the encapsulation efficiency was up to (78.7 ± 6.9)%.Comparing to the normal gel,(CPT gel),the cumulative penetration amount and the re-tention amount in the skin of the nanogels (CPT-PPO gel,CPT-PP gel) were significant higher (P＜0.01),the retention and cumulative penetration amount of CPT-PPO gel was significant higher than that of CPT-PP gel (P＜0.05).Conclusion After modified by OA,CPT-PPO gel can increase the cumulated amount and absorption in skin and can be used as a carrier of CPT in the new formulation for topical treatment of psoriasis.
ABSTRACT
In this study, we prepared various matrices of hydrogel patches and studied their cross-linking mechanism by observing their rheological properties, which could provide theoretical basis and deep technical support for further industrial development of hydrogel patch. Rheology method was used to do the amplitude scanning and single-frequency scanning for various hydrogel matrix, under the condition of oscillation mode of the rheometer. Then the linear viscoelastic region, composite modulus value, as well as changes in slope with time of the composite modulus and phase angle of various hydrogel matrix were analyzed in detail. The results showed that the stability of matrix was mainly determined by hydrogel frame; only in acidic environment, the cross-linking reaction between cross-linker and hydrogel frame can occur; elasticity of matrix can be decreased by organic acid and the effect level was related to the ratio of the number of carboxyl and hydroxyl (-COO(-)/-OH) in adjusters: if the ratio was not equal, the higher -COO(-)/-OH in adjusters would be the less elasticity of matrix decreased; the cross-linking speed of matrix was determined by adjuster, the cross-linking speed of matrix contain different adjusters was ranged in following order: matrix containing tartaric acid > matrix containing lactic acid > matrix containing malic acid > matrix containing citric acid; the cross-linking speed of matrix was not uniform in the whole cross-linking process.