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Testosterone Sustained Release Microspheres for the Treatment of Fecal Incontinence

The objective of this study was to develop a testosterone sustained release formulation for the treatment of fecal incontinence. To suppress the initial burst release of testosterone, which can lead to systemic toxicity, we incorporated a washing step using an aminoalkyl methacrylate copolymer E sol...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2022-08, Vol.111 (8), p.2322-2329
Main Authors: Oe, Yusuke, Ogino, Shinichi, Kobayashi, Masanori, Kojima, Hiroyuki, Terukina, Takayuki, Kanazawa, Takanori, Kondo, Hiromu
Format: Article
Language:English
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Summary:The objective of this study was to develop a testosterone sustained release formulation for the treatment of fecal incontinence. To suppress the initial burst release of testosterone, which can lead to systemic toxicity, we incorporated a washing step using an aminoalkyl methacrylate copolymer E solution or propylene glycol solution into a typical o/w emulsion method to prepare polylactic-co-glycolic acid microspheres. We used this method to develop a polylactic-co-glycolic acid microsphere formulation that shows sustained release of testosterone for up to one month. Not only did this formulation show a sustained release profile after administration into the intersphincteric groove in minipigs, it also increased both the anal pressure and mass of the external anal sphincter, while keeping systemic testosterone exposure low. Thus, this formulation successfully affected both the internal and external anal sphincters with a sufficient safety profile, deeming it a promising candidate treatment strategy for fecal incontinence. [Display omitted] •PLGA microspheres showed sustained release of testosterone for one month.•Washing microspheres with propylene glycol solution suppressed the initial burst.•The low systemic testosterone exposure suggests a low risk of toxicity.•Microspheres showed effects on both the internal and external anal sphincters.•Testosterone microspheres are promising for the treatment of fecal incontinence.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2022.03.008