Correction: Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of Niemann-Pick Disease type C1.

[This corrects the article DOI: 10.1371/journal.pone.0175478.].

Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of Niemann-Pick Disease type C1.

2-Hydroxypropyl-beta-cyclodextrin (HPßCD) has gained recent attention as a potential therapeutic intervention in the treatment of the rare autosomal-recessive, neurodegenerative lysosomal storage disorder Niemann-Pick Disease Type C1 (NPC1). Notably, HPßCD formulations are not comprised of a single molecular species, but instead are complex mixtures of species with differing degrees of hydroxypropylation of the cyclodextrin ring. The degree of substitution is a critical aspect of the complex mixture as it influences binding to other molecules and thus could potentially modulate biological effects. VTS-270 (Kleptose HPB) and Trappsol® Cyclo™ are HPßCD products under investigation as novel treatments for NPC1. The purpose of the present work is to compare these two different products; analyses were based on ion distribution and abundance profiles using mass spectrometry methodology as a means for assessing key molecular distinctions between products. The method incorporated electrospray ionization and analysis with a linear low-field ion mobility quadrupole time-of-flight instrument. We observed that the number of hydroxypropyl groups (the degrees of substitution) are substantially different between the two products and greater in Trappsol Cyclo than in VTS-270. The principal ions of both samples are ammonium adducts. Isotope clusters for each of the major ions show doubly charged homodimers of the ammonium adducts. In addition, both products show doubly charged homodimers from adduction of both a proton and ammonium. Doubly charged heterodimers are also present, but are more intense in Trappsol Cyclo than in VTS-270. Based on the analytical differences observed between VTS-270 and Trappsol Cyclo with respect to the degree of substitution, the composition and fingerprint of the complex mixture, and the impurity profiles, these products cannot be considered to be the same; the potential biological and clinical implications of these differences are not presently known.

Clinical guidance on the use of live attenuated influenza vaccine after inadvertent freezing and warming.

The immediate and long-term impact of temperature deviations that may occur in clinical practice on live attenuated influenza vaccine (LAIV) potency was examined in four distinct studies that exposed vaccine to freeze/thaw cycles, warming, and heating conditions. No significant loss of vaccine potency was observed after three freeze/thaw cycles, warming of vaccine to 15°C (59°F) for 72 hours or less, exposure to room temperature (25°C/77°F) for 12 hours or less, or after heating to 37°C (99°F) for 6 hours or less. The results of these studies demonstrate that LAIV potency can potentially be maintained after exposure to temperature deviations. If a particular annual formulation of LAIV is exposed to temperatures outside of the recommended storage range, practitioners should contact the manufacturer for guidance regarding proper vaccine handling.