PLGA nanoparticles and nanosuspensions with amphotericin B: Potent in vitro and in vivo alternatives to Fungizone and AmBisome.

This paper describes the development of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) and nanosuspensions with the polyene antibiotic amphotericin B (AmB). The nanoformulations were prepared using nanoprecipitation and were characterised with respect to size, zeta potential, morphology, drug crystallinity and content. Standard in vitro sensitivity tests were performed on MRC-5 cells, red blood cells, Leishmania infantum promastigotes and intracellular amastigotes and the fungal species Candida albicans, Aspergillus fumigatus and Trichophyton rubrum. The in vivo efficacy was assessed and compared to that of Fungizone and AmBisome in the acute A. fumigatus mouse model at a dose of 2.5 and 5.0mg/kg AmB equivalents. The developed AmB nanoformulations were equivalently or more effective against the different Leishmania stages and axenic fungi in comparison with the free drug. The in vitro biological activity, and especially hemolytic activity, clearly depended on the preparation parameters of the different nanoformulations. Further, we demonstrated that the superior in vitro antifungal activity could be extrapolated to the in vivo situation. At equivalent dose, the optimal AmB-loaded PLGA NP was about two times and the AmB nanosuspension about four times more efficacious in reducing the total burden than AmBisome. The developed AmB nanomedicines could represent potent and cost-effective alternatives to Fungizone and AmBisome.

Adenoids and tonsils, indications for surgery and immunological consequences of surgery.

Tonsillectomy and adenoidectomy procedures are among the oldest surgical procedures still performed today. Tonsils and adenoids are part of Waldeyer's ring, the basic function of which is antibody formation. Because of their location at the portal of entry of many airborne and alimentary antigens, the tonsils and adenoids often have been considered as the first line of defense against respiratory infections. Indications for adenoidectomy or tonsillectomy are to date still controversial. The two main indications for tonsillectomy are upper airway obstruction due to tonsillar hypertrophy and recurrent acute or chronic tonsillitis. Adenoid hypertrophy with upper airway or eustachian tube obstruction and recurrent acute or chronic adenoiditis or otitis media are main indications to perform an adenoidectomy. The possible immunological effects of tonsillectomy and adenoidectomy are still controversial. Some authors have found changes in immunoglobulin levels after tonsillectomy, while others failed to find significant changes. In a review of long-term follow-up studies, the authors showed that while tonsillectomy may lead to certain changes in the cellular and humoral immune system, these alterations are clinically insignificant and no increased frequency of immunomodulated diseases should be expected.