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Abstract Purpose  To investigate the potential of a novel lipid carrier, comprising beads of alpha-cyclodextrin and soybean oil, for topical drug delivery. Adapalene was chosen as a model drug to explore the ability of the beads to encapsulate and release a highly lipophilic compound. Materials and Methods  Adapalene-loaded beads were prepared and characterised. Skin tolerance to unloaded beads was tested on human volunteers, while drug release and delivery into stratum corneum, was evaluated in pig skin ex vivo. Results  The preparation and physical characteristics of the beads were not dependent on whether adapalene had been previously dissolved or dispersed in soybean oil. Drug encapsulation efficiency was high (>96%) and drug loading on the order of a therapeutic level could be achieved in freeze-dried beads prepared from an oily dispersion of adapalene. After application to human skin, unloaded beads induced no adverse reaction and were better tolerated than an alcoholic gel. Tape-stripping the stratum corneum from treated pig skin showed that adapalene release and penetration from the beads was comparable to that from gel and cream formulations available on the market. Conclusion  These novel beads may offer a well-tolerated and efficient system for the encapsulation and topical delivery of lipophilic drugs. [ABSTRACT FROM AUTHOR]

Abstract

Purpose. Antisense oligonucleotides (AON) against junction EWSFli-1 oncogene (which is responsible for the Ewing Sarcoma) are particularly interesting for targeting chromosomal translocations that are only found in tumor cells. However, these AON have proved in the past to be ineffective in vivo because of their susceptibility to degradation and their poor intracellular penetration. The aim of this study was to improve the delivery of these molecules through the use of nanotechnologies. Method Two different AONs, and their controls, both targeted against the junction area of the fusion gene EWS-Fli-1 were used. Nanocapsules were employed to deliver a phosphorothioate AON and its control. The nanospheres were used to deliver a chimeric phosphorothioate, phosphodiester AON, with 5 additional bases in 5' which allow this AON to be structured with a loop. These formulations were injected intratumorally to nude mice bearing the experimental EWS-FIi-1 tumor. The tumour volume was estimated during the experiments by two perpendicular measurements length (a) and width (b) of the tumour and was calculated as ab[sup2]/2. Northern blot analysis was also performed after removing the tumors 24 h after the treatment with a single dose of AON either free or associated with nanotechnologies. Results. This study shows for the first time that AON against EWSFli-1 oncogene may inhibit with high specificity the growth of an EWS-Fli-1 dependent tumor grafted to nude mice provided they are delivered by nanocapsules or nanospheres. In this experience, the antisense effect was confirmed by the specific down regulation of EWS-Fli-1 mRNA. Conclusion. Thus, both nanocapsules and nanospheres may be considered as promising systems for AON delivery in vivo. [ABSTRACT FROM AUTHOR]