Antitumoral activity of camptothecin-loaded nanoparticles in 9L rat glioma model.

Camptothecin (CPT), a plant alkaloid, is a potent anticancer drug in cell culture studies but it is clinically inactive due to rapid hydrolysis under physiological conditions. The drug exists in two forms depending on the pH value, an active lactone form at pH below 5 and an inactive carboxylate form at basic pH and this is a reversible reaction. In this study, nanoparticulate delivery systems were developed with either amphiphilic cyclodextrins, poly(lactide-co-glycolide) or poly-ɛ-caprolactone in order to maintain the active lactone form and prevent the drug from hydrolysis. All nanoparticles were prepared with nanoprecipitation technique. Mean particle sizes were 130-280nm and surface charges were negative. The encapsulation efficiency was significantly higher for amphiphilic cyclodextrin nanoparticles when compared to polymeric nanoparticles. Nanoparticle formulations based on cyclodextrins showed a controlled release profile extended up to 12 days. 6-O-Capro-ß-cyclodextrin (1.44µg/60µL CPT) and concentrated 6-O-Capro-ß-cyclodextrin (2.88µg/60µL CPT) nanoparticles significantly modified the growth or lethality of the 9L gliomas, since the median survival time was 26 days for the untreated group and between 27 and 33 days for amphiphilic cyclodextrin nanoparticle groups. These results indicate that, CPT-loaded amphiphilic cyclodextrin nanoparticles may provide a promising carrier system for the effective delivery of CPT in comparison to polymeric analogues.

Antibacterial activity of triclosan chitosan coated graft on hernia graft infection model.

The use of mesh in hernia repair has become common, because of lower recurrence rate and simple application. Data from the meta-analysis and the multi-central studies support the use of meshes in hernia repair. One of the complications due to the hernia repair with mesh is the infection. The incidence range is between 1 and 10%. Triclosan embedded commercial absorbable suture materials are used to reduce surgical site infection rate. This study was planned on mesh infection model, because of the low incidence rate. The agent isolated from mesh infections was mostly Staphylococcus aureus and thus it was used as the infecting agent in this research. To achieve a better therapeutic efficacy, triclosan was formulated in chitosan gels. Chitosan is an attractive biopolymer because of its biocompatible, biodegradable, bioadhesive properties. Gel formulations using chitosans (low, medium and high molecular weight) were prepared in 1% (v/v) acetic acid solution and in vitro release profiles were evaluated. Gel formulations showed release profile extended up to 7 days and high molecular weight chitosan gel formulation was released higher quantity drug than other formulations. Meshes coated with triclosan loaded chitosan gel were used to reduce bacterial count and to prevent mesh infection in the study. 24h and simultaneous bacteria inoculation was used to model mesh infection. The rats were observed for 8 days by means of surgical site infection. On the eighth day, the animals were sacrificed and the grafts were removed. Tissue squeezers were used to liberate bacterias from removed grafts. The isolated suspensions were cultured on blood agar plates and colony-forming units were counted overnight. Grafts coated with triclosan loaded chitosan gel presented satisfactory preventive effect against graft infection.

Comparative evaluation of polymeric and amphiphilic cyclodextrin nanoparticles for effective camptothecin delivery.

Camptothecin (CPT) is a potent anticancer agent. The clinical application of CPT is restricted by poor water solubility and instability under physiological conditions. Solubilization and stabilization of CPT were realized through nanoparticulate systems of amphiphilic cyclodextrins, poly(lactide-co-glycolide) (PLGA) or poly-epsilon-caprolactone (PCL). Nanoparticles were prepared with nanoprecipitation technique, whereas cyclodextrin nanoparticles were prepared from preformed inclusion complexes of CPT with amphiphilic cyclodextrins. Polymeric nanoparticles, on the other hand, were loaded with CPT:HP-beta-CD inclusion complex to solubilize and stabilize the drug. Mean particle sizes were under 275 nm, and polydispersity indices were lower than 0.2 for all formulations. Drug-loading values were significantly higher for amphiphilic cyclodextrin nanoparticles when compared with those for PLGA and PCL nanoparticles. Nanoparticle formulations showed a significant controlled release profile extended up to 12 days for amphiphilic cyclodextrin nanoparticles and 48h for polymeric nanoparticles. Anticancer efficacy of the nanoparticles was evaluated in comparison with CPT solution in dimethyl sulfoxide (DMSO) on MCF-7 breast adenocarcinoma cells. Amphiphilic cyclodextrin nanoparticles showed higher anticancer efficacy than PLGA or PCL nanoparticles loaded with CPT and the CPT solution in DMSO. These results indicated that CPT-loaded amphiphilic cyclodextrin nanoparticles might provide a promising carrier system for the effective delivery of this anticancer drug having bioavailability problems.

Formulation and in-vitro characterization of retinoic acid loaded poly (lactic-co-glycolic acid) microspheres.

Poly (lactic-co-glycolic acid) (PLGA) microspheres containing all-trans retinoic acid (atRA) were prepared by emulsion/solvent evaporation technique. PLGA (50:50) with inherent viscosities of 0.17 and 0.39 dL g(-1) was used. Polyvinyl alcohol (PVA) or PVA and sodium oleate (SO) combinations (4:1) were used to stabilize the emulsions. The effect of polymer viscosity, emulsifier type and concentration on the in vitro release of atRA from the microspheres was investigated. The stability of the microparticles was also tested at the temperatures of 4, 25 and 40 degrees C. The particle size ranged between 1-2 microm. Microspheres were smooth and spherical in shape, as determined by scanning electron microscope (SEM) photographs. The yield of microspheres ranged from 50-75% and the encapsulation efficiency was determined between 45-75%. In vitro release studies showed that atRA release from microspheres lasted for 11 days.