Intratumoral Injection Administration of Irinotecan-Loaded Microspheres: In Vitro and In Vivo Evaluation.

To reduce the toxic and side effects of intravenous chemotherapeutic drugs on the tumor-patients, the aims of this study were to design and study intratumor-administrated irinotecan-loaded PLGA microspheres (CPT-11-PLGA-MS) in vitro and in vivo according to the structure characteristics of CPT-11. PLGA microspheres containing irinotecan were prepared by emulsion solvent evaporation method and evaluated in terms of their morphology, particle size analysis, in vitro drug release, drug retention and leakage studies in vivo, and pharmacodynamics studies. The CPT-11-PLGA-MS were spherical with mean size of 9.29 ± 0.02 µm, and average encapsulation efficiency were measured of 77.97 ± 1.26% along with the average drug loading of 7.08 ± 0.11%. DSC results indicated that the drug existed in the phase of uncrystallization in the microspheres. The formulation of CPT-11-PLGA-MS could prolong the in vitro drug release to 16 days following Weibull equation. In CPT-11-PLGA-MS after intratumor injection administration was significantly improved. The results demonstrated that the slow-sustained release of CPT-11-PLGA-MS in tumor tissue after intratumor injection of microspheres can reduce the drug leakage to the circulation system, maintain the drug retention, and improve the therapeutic effect, which could become a promising drug delivery system for CPT-11 and could maintain the most effective concentration at the target site to maximum limit.

[Orthogonal experiments for optimizing the formulation and preparation conditions of temozolomide solid lipid nanoparticles].

TMZ-SLN were prepared by emulsification-low temperature solidification method with stearic acid. The formulation and the preparation conditions were optimized by orthogonal experiments using entrapment efficiency as the evaluation index. The morphology was detected by transmission electron microscope. The Zeta potentials and the particle size distribution were evaluated by Laser Doppler Anemometry. The entrapment efficiencies and the drug release characteristics in vitro were assessed. The result showed that TMZ-SLN were concinnous and spherical in shape. The mean diameter (d(av) ) was 65.0 +/- 6.2 nm and the Zeta potential was -37.2 mV. The average entrapment efficiency was 58.9% +/- 1.21 %. The drug release behavior in vitro conformed to Higuchi Equation. The formation of a new material phase was testified by analysis of differential scanning calorimetry.

Solid lipid nanoparticles of temozolomide: potential reduction of cardial and nephric toxicity.

The aim of this study was to prepare temozolomide solid lipid nanoparticles (TMZ-SLNs), to evaluate its physiochemical characteristics, and to investigate the specific drug targeting of intravenous (i.v.) injected solid lipid nanoparticles of temozolomide. TMZ-SLNs was prepared by an emulsification and low-temperature solidification method. In vitro drug release was conducted in phosphate-buffered saline (pH 6.8) at 37 degrees C. The concentrations of the temozolomide in selected organs were determined using reversed-phase high-performance liquid chromatography (HPLC) following i.v. administration of the TMZ-SLNs and a temozolomide solution (TMZ-Sol). The results show that the TMZ-SLNs had an average diameter of 65.9+/-11.8nm with a zeta potential of -37.2+/-3.6mV and the in vitro drug release was monitored for up to 3 days, and the release behavior was in accordance with Higuchi-equation. In the tested organs, the AUC/dose and the mean residence times (MRT) of the TMZ-SLNs were much higher and longer than those of the TMZ-Sol, especially in brain and reticuloendothelial cells-containing organs. The AUC ratio of TMZ-SLNs to TMZ-Sol in the brain was the highest among the organs. These results indicated that the SLNs is a promising sustained-release and drug-targeting system for antitumor drugs. It may also allow a reduction in dosage and a decrease in systemic toxicity.