Absorption of oligodeoxynucleotide by suppository from rat rectal route

Area of Science:

• Pharmacology
• Drug Delivery
• Biochemistry

Background:

• Phosphorothioate deoxynucleotides (S-Oligos) are utilized in various therapeutic applications.
• Efficient rectal absorption of oligonucleotides remains a challenge for systemic drug delivery.
• Developing effective rectal delivery systems is crucial for non-invasive oligonucleotide therapeutics.

Purpose of the Study:

• To investigate the rectal absorption of 32-mer phosphorothioate deoxynucleotides (S-Oligo) in rats.
• To evaluate the efficacy of a suppository formulation containing oleic acid and a surfactant as a rectal absorption enhancer.
• To determine the pharmacokinetic profile of S-Oligo following rectal administration.

Main Methods:

• Rats were administered 32-mer S-Oligo via suppositories with varying concentrations of oleic acid and a surfactant.
• Blood samples were collected at different time points post-administration.
• S-Oligo concentrations in blood were quantified using appropriate analytical techniques.

Main Results:

• Suppositories without oleic acid did not result in detectable blood levels of S-Oligo.
• Suppositories containing over 10% oleic acid facilitated detectable rectal absorption of S-Oligo in rats.
• The maximum concentration (tmax) of S-Oligo in blood was observed at 2 hours postdosing.

Conclusions:

• Oleic acid, particularly at concentrations above 10%, significantly enhances the rectal absorption of 32-mer S-Oligo in rats.
• Suppository formulations incorporating oleic acid show promise as a viable rectal delivery system for oligonucleotides.
• Further research into optimizing suppository formulations could lead to improved non-invasive oligonucleotide-based therapies.