Self-expandable metallic stent-induced esophagorespiratory fistulas in patients with advanced esophageal cancer

Background/Aims@#Self-expandable metallic stents (SEMSs) are widely adopted for the palliation of dysphagia in patients with malignant esophageal strictures. An important adverse event is the development of SEMS-induced esophagorespiratory fistulas (SEMS-ERFs). This study aimed to assess the risk factors related to the development of SEMS-ERF after SEMS placement in patients with esophageal cancer. @*Methods@#This retrospective study was performed at the Instituto do Cancer do Estado de São Paulo. All patients with malignant esophageal strictures who underwent esophageal SEMS placement between 2009 and 2019 were included in the study. @*Results@#Of the 335 patients, 37 (11.0%) developed SEMS-ERF, with a median time of 129 days after SEMS placement. Stent flare of 28 mm (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.15–5.51; p=0.02) and post-stent chemotherapy (HR, 2.0; 95% CI, 1.01–4.00; p=0.05) were associated with an increased risk of developing SEMS-ERF, while lower-third tumors were a protective factor (HR, 0.5; 95% CI, 0.26–0.85; p=0.01). No difference was observed in overall survival. @*Conclusions@#The incidence of SEMS-ERFs was 11%, with a median time of 129 days after SEMS placement. Post-stent chemotherapy and a 28 mm stent flare were associated with a higher risk of SEMS-ERF.

Spray-dried chitosan/ethylcellulose microspheres for nasal drug delivery: swelling study and evaluation of in vitro drug release properties.

The aim of this study was to develop spray-dried chitosan-based microspheres, suitable for nasal delivery of loratadine, and to evaluate their potential of modifying loratadine release. The microspheres were composed with ethylcellulose (EC) and chitosan (CM) in two different weight ratios, 1:2 and 1:3. One-phase systems (dispersions) and two-phase systems (emulsions and suspensions) were subjected to spray-drying, resulting in conventional and composed microspheres, respectively. The microspheres were evaluated with respect to the yield, particle size, encapsulation efficiency, physical state of the drug in the polymer matrix, swelling properties and in vitro drug release profile. It was shown that particle size, swelling ability and loratadine release from spray-dried microspheres were significantly affected by the polymeric composition and feed concentration in spray-drying process. Emulsifying method to produce composed EC/CM microspheres resulted in improved loratadine entrapment and moderate swelling, when compared to conventional chitosan microspheres. It seems like better formation of EC cores and chitosan coating were obtained when higher feed concentration and ultrasonic homogenization were employed in the preparation of emulsion systems and when EC to CM weight ratio was 1:3.

Development and bioadhesive properties of chitosan-ethylcellulose microspheres for nasal delivery.

Loratadine-loaded microspheres were prepared by spray-drying of dispersions, emulsions and suspensions differing in polymeric composition and solvents used. Conventional microspheres were obtained by spray-drying of dispersions composed of chitosan (CM) as only polymer, while composed microspheres were obtained by spray-drying of two-phase systems composed of chitosan and ethylcellulose (EC). Microspheres differed in EC/CM weight ratio (0:1, 1:2 and 1:3) and in loratadine/polymers weight ratio (1:6 and 1:8). The entrapment efficiencies were between 67.9 and 86.1%; less loratadine was entrapped as polymer/drug ratio decreased. In comparison to one-phase systems composed of CM as only polymer, spray-drying of two-phase systems composed of both, CM and EC resulted in improved loratadine entrapment (80.1-86.1%). All microspheres were positively charged, indicating the presence of chitosan at the surface, regardless of the drug content and the type of spray-dried system. The highest zeta-potential was measured for loratadine-free conventional microspheres, consisting of chitosan only (32.7+/-1.3 mV). Tensile studies showed that both, EC/CM ratio and the type of spray-dried system influenced the bioadhesive properties of the microspheres in a way that the microspheres with higher chitosan content were more bioadhesive and microspheres prepared from suspensions were more bioadhesive than those prepared from emulsions, regardless of the same polymeric composition. The results suggested that the spray-drying method is useful to produce bioadhesive loratadine-loaded microspheres.

Synthesis and characterization of thiomers of polyaspartamide type.

Synthesis of poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)]-thioglycolic acid (PHEA-TGA) conjugate as a new polyaspartamide thiomer is described. The parent polymer PHEA is chemically modified by introducing sulphydryl-bearing compound thioglycolic acid. By varying the reaction conditions several batches of PHEA-TGA conjugates were prepared and analyzed. Tensile studies revealed that total work of adhesion of PHEA-TGA increased more than twice compared to the unmodified polymer. Microparticles prepared from the thiolated polymer preserved its bioadhesive properties.

[Liberation of folic acids from composite chitosan films]. / Liberace kyseliny listové z kompozitních chitosanových filmu.

Thin films were prepared by the method of evaporation of aqueous solutions of chitosan or its mixtures with poloxamer 407, gelatin, or polyvinyl alcohol. Films of varying thickness were cross-linked with phosphate ions. They contained micronized folic acid in a concentration of 9.1% or 3.2%. Prolonged several hours' liberation of folic acid into isotonic phosphate buffer at pH 5.5, 6.0, and 6.5 was examined. In the initial stage, the mechanism of liberation was governed by diffusion of the dissolved fraction, at higher pH values a higher rate of dissolution of the substance played its role. In some composites, sorption of folic acid to chitosan in an extent dependent on the composition of composites and current acidity of the medium was demonstrated.