Preparation and in vitro evaluation of 5-fluorouracil-loaded PCL nanoparticles for colon cancer treatment.

Nanoparticles loaded with 5-fluorouracil (5-FU) for colon cancer therapies were prepared using the solvent evaporation technique, which involved lyophilization by freeze-drying. Formulations produced a substantially high encapsulation efficiency of approximately 93%. A positive correlation was seen when increasing polycaprolactone (PCL) and/or PVA concentrations and the size of nanoparticles produced. Increasing PCL concentration had a considerable influence on PDI while increasing PVA concentration had a lesser effect. All nanoparticles possessed a negative zeta potential, particularly in formulations with low polymer and polymer emulsifier concentrations. The formulation with the lowest PCL and PVA concentration was characterized by the most optimal properties; which accounts for the desirable delayed release profile of the active drug in dissolution testing indicating an improved targeting capability and enhanced bioavailability at the action site. Cytotoxicity studies showed that 5-FU loaded PCL nanoparticles had higher antiproliferative effect than free 5-FU on Caco-2 cell line (p < 0.05). The encouraging results obtained offer reasons for optimism regarding the future of 5-FU nanoparticles as a promising drug delivery system which could be further improved by including either enteric coating or encapsulating the nanoparticles onto microparticles to overcome unanticipated degradation.

Effect of locally applied transforming growth factor Beta3 on wound healing and stenosis development in tracheal surgery.

BACKGROUND: Tracheal stenosis constitutes one of the most frequently seen problems in thoracic surgery. Although many treatment modalities to prevent fibroblast proliferation, angiogenesis, or inflammation that causes tracheal stenosis have been attempted, an effective method has not yet been found. In this study, a transforming growth factor beta3 (TGF-ß3)/chitosan combination was used for this purpose. METHODS: A slow-release preparation containing a thin layer of TGF-ß3 with a chitosan base was made. Thirty albino Wistar rats were divided into 3 groups. A full-layer vertical incision was made in the anterior side of the trachea of each rat between the second and fifth tracheal rings. The tracheal incision was sutured. Group A was evaluated as the control group. In Group B, a chitosan-based film was placed on the incision line. In Group C, a slow-release TGF-ß3/chitosan-coated substance was placed on the incision line. The rats were killed on day 30, and their tracheas were excised by cutting between the lower edge of the thyroid cartilage and the upper edge of the sixth tracheal ring together with the esophagus. Epithelialization, fibroblast proliferation, angiogenesis, inflammation, and collagen levels were evaluated histopathologically by the same histopathologist. RESULTS: Statistically significant differences were not found among the 3 groups. Cold abscesses were observed at the incision sites in both the TGF-ß/chitosan and chitosan groups. These were thought to have formed due to the chitosan. CONCLUSIONS: As this was the first experiment in the literature to use this type of TGF-ß3 formulation, we intend to change the formulation and perform this study again with a different TGF-ß3/chitosan preparation.

Sulindac loaded alginate beads for a mucoprotective and controlled drug release.

Ionotropic gelation was used to entrap sulindac into calcium alginate beads as a potential drug carrier for the oral delivery of this anti-inflammatory drug. Beads were investigated in vitro for a possible sustained drug release and their use in vivo as a gastroprotective system for sulindac. Process parameters such as the polymer concentration, polymer/drug ratio, and different needle diameter were analysed for their influences on the bead properties. Size augmented with increasing needle diameter (0.9 mm needle: 1.28 to 1.44 mm; 0.45 mm needle: 1.04 to 1.07 mm) due to changes in droplet size as well as droplet viscosity. Yields varied between 87% and 98% while sulindac encapsulation efficiencies of about 88% and 94% were slightly increasing with higher alginate concentrations. Drug release profiles exhibited a complete release for all formulations within 4 hours with a faster release for smaller beads. Sulindac loaded alginate beads led to a significant reduction of macroscopic histological damage in the stomach and duodenum in mice. Similarly, microscopic analyses of the mucosal damage demonstrated a significant mucoprotective effect of all bead formulation compared to the free drug. The present alginate formulations exhibit promising properties of a controlled release form for sulindac; meanwhile they provide a distinct tissue protection in the stomach and duodenum.

Lipid nanocapsule size analysis by hydrodynamic chromatography and photon correlation spectroscopy.

Particle size and the size distribution are known to be important factors in the overall behavior of nanoparticulate drug delivery systems and an exact determination of these parameters is highly important. Several techniques are applied in the size determination of nanoparticulates, particularly dynamic light scattering. Also other methods have been proposed, among them hydrodynamic chromatography (HDC). In order to characterize a HDC method for nanosized carriers, differently sized lipid nanocapsules having a diameter of 25-100 nm were analyzed and results were compared with measurements from photon correlation spectroscopy (PCS) and atomic force microscopy. Results from atomic force microscopy studies were generally not in line with determinations from the other techniques due to a particle shape loss by the drying step. PCS and HDC led to comparable results in simple size determination of lipid nanocapsules. However, slight differences were found during the characterization of more complex samples. HDC was able to detect micelles as a byproduct of nanocapsule preparation while in PCS the sample dilution turned micelles undetectable. HDC analysis was able to characterize mixed samples of particle batches differing in their average size similar to PCS. HDC was found to be an excellent tool for the determination of size and average size distribution of lipid nanocapsules.