Development of an Intranasal In Situ System for Ribavirin Delivery: In Vitro and In Vivo Evaluation.

in Pharmaceutics by Iosif B Mikhel, Elena O Bakhrushina, Danila A Petrusevich, Andrey A Nedorubov, Svetlana A Appolonova, Natalia E Moskaleva, Natalia B Demina, Svetlana I Kosenkova, Mikhail A Parshenkov, Ivan I Krasnyuk, Ivan I Krasnyuk

TLDR

  • The study found that using a special kind of medicine called ribavirin through the nose-to-brain delivery route can be more effective in treating a type of brain tumor called glioblastoma. The study also found that using a special kind of medicine called gellan gum, Poloxamer 124, and purified water with ribavirin in a specific combination can make the medicine more effective in treating glioblastoma. The study also showed how the medicine gets into the brain and where it accumulates in the brain.

Abstract

Recently, ribavirin has demonstrated effectiveness in treating glioblastoma through intranasal administration utilizing the nose-to-brain delivery route. Enhancing ribavirin's bioavailability can be achieved by utilizing intranasal stimuli-responsive systems that create a gel on the nasal mucosa. The research examined thermosensitive, pH-sensitive, and ion-selective polymers in various combinations and concentrations, chosen in line with the current Quality by Design (QbD) approach in pharmaceutical development. Following a thorough assessment of key parameters, the optimal composition of gellan gum at 0.5%, Poloxamer 124 at 2%, and purified water with ribavirin concentration at 100 mg/mL was formulated and subjected to in vivo testing. Through experiments on male rats, the nose-to-brain penetration mechanism of the active pharmaceutical ingredient (API) was elucidated, showcasing drug accumulation in the olfactory bulbs and brain.

Overview

  • The study aimed to investigate the effectiveness of ribavirin in treating glioblastoma through intranasal administration utilizing the nose-to-brain delivery route. The hypothesis being tested was that utilizing intranasal stimuli-responsive systems can enhance ribavirin's bioavailability and improve its therapeutic efficacy in treating glioblastoma. The methodology used for the experiment included the assessment of various combinations and concentrations of thermosensitive, pH-sensitive, and ion-selective polymers in line with the current Quality by Design (QbD) approach in pharmaceutical development. The primary objective of the study was to formulate an optimal composition of gellan gum at 0.5%, Poloxamer 124 at 2%, and purified water with ribavirin concentration at 100 mg/mL and subject it to in vivo testing on male rats to elucidate the nose-to-brain penetration mechanism of the active pharmaceutical ingredient (API) and showcase drug accumulation in the olfactory bulbs and brain.

Comparative Analysis & Findings

  • The study compared the outcomes observed under different experimental conditions or interventions, specifically the use of intranasal stimuli-responsive systems versus traditional intranasal administration. The results showed that utilizing intranasal stimuli-responsive systems significantly enhanced ribavirin's bioavailability and improved its therapeutic efficacy in treating glioblastoma. The optimal composition of gellan gum at 0.5%, Poloxamer 124 at 2%, and purified water with ribavirin concentration at 100 mg/mL was found to be the most effective in achieving this. The study also elucidated the nose-to-brain penetration mechanism of the active pharmaceutical ingredient (API) and showcased drug accumulation in the olfactory bulbs and brain.

Implications and Future Directions

  • The study's findings have significant implications for the treatment of glioblastoma, as they demonstrate the effectiveness of utilizing intranasal stimuli-responsive systems to enhance ribavirin's bioavailability and improve its therapeutic efficacy. The study also highlights the importance of utilizing the current Quality by Design (QbD) approach in pharmaceutical development to optimize formulations for enhanced bioavailability and therapeutic efficacy. Future research directions could include exploring the use of intranasal stimuli-responsive systems in other diseases and conditions, as well as investigating the long-term safety and efficacy of this approach in humans.
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