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Updated: Jul 9, 2026
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Control of cardiotoxicity via nasal in-situ pH-sensitive transbilosomal formulation of candesartan
Mohamed A M Ali1, Amany Belal2, Fatma I Abo El-Ela3
1Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), 11623, Riyadh, Saudi Arabia.
Abstract:
Candesartan (CDN) is a potent antagonist of the angiotensin II receptor known for its protective effects against cardiotoxicity. However, the oral administration of CDN exhibits limited therapeutic effectiveness due to factors such as first-pass hepatic metabolism, low solubility, and low bioavailability. This study's primary objective was to improve the cardioprotective efficacy of CDN in mitigating cardiotoxicity by developing a nasal in situ pH-sensitive formulation of CDN-loaded transbilosomes (ISPCLT). The Box-Behnken design was used to identify the optimal CDN-loaded transbilosome (CLT) formulation. The ISPCLT formulation was then developed by mixing the optimal CLT formulation with a mixture of chitosan and glyceryl monooleate. The bioavailability and efficacy of the ISPCLT formulation were examined in a cardiotoxicity rat model. The optimal CLT formulation consists of 262.6 mg of phospholipid, 20.4 mg of Span 60, and 10.2 mg of sodium deoxycholate. The ISPCLT formulation demonstrated a 2.55-fold increase in CDN release, a 7.04-fold increase in CDN permeation, and a 5.13-fold increase in CDN bioavailability compared to the free CDN suspension. The nasal ISPCLT formulation resulted in a 62.14% increase in body weight, a 95.98% decrease in lactate dehydrogenase levels, and a 93.39% reduction in CK-MB isoenzyme-MB levels when compared to the oral CDN suspension. Histopathological examination validated the ISPCLT formulation's cardioprotective action. The nasal ISPCLT formulation enhances patient adherence and minimizes the risk of adverse effects by allowing for lower dosages. The findings suggest that new strategies for managing cardiotoxicity may be viable with the nasal ISPCLT formulation.
Insights
A novel nasal formulation of Candesartan (CDN) transbilosomes significantly improved its effectiveness against cardiotoxicity in rats. This enhanced delivery system boosts bioavailability and reduces cardiac damage markers, offering a promising alternative to oral CDN.
Area of Science:
- Pharmacology and Drug Delivery
- Cardiovascular Research
- Nanotechnology in Medicine
Background:
- Candesartan (CDN) is an angiotensin II receptor antagonist with cardioprotective properties.
- Oral CDN administration shows limited efficacy due to poor bioavailability and first-pass metabolism.
- Developing advanced delivery systems is crucial for enhancing CDN's therapeutic potential against cardiotoxicity.
Purpose of the Study:
- To develop and evaluate a nasal in situ pH-sensitive formulation of Candesartan-loaded transbilosomes (ISPCLT) for improved cardioprotection.
- To optimize the Candesartan-loaded transbilosome (CLT) formulation using a Box-Behnken design.
- To assess the enhanced bioavailability and efficacy of the ISPCLT formulation in a rat model of cardiotoxicity.
Main Methods:
- Optimization of Candesartan-loaded transbilosomes (CLT) using Box-Behnken design.
- Formulation of nasal in situ pH-sensitive Candesartan-loaded transbilosomes (ISPCLT) with chitosan and glyceryl monooleate.
- Evaluation of CDN release, permeation, bioavailability, and cardioprotective effects in a cardiotoxicity rat model.
Main Results:
- The optimal CLT formulation contained specific concentrations of phospholipid, Span 60, and sodium deoxycholate.
- ISPCLT demonstrated significantly increased CDN release (2.55-fold), permeation (7.04-fold), and bioavailability (5.13-fold) compared to free CDN.
- Nasal ISPCLT treatment led to improved body weight, reduced lactate dehydrogenase (95.98%), and CK-MB isoenzyme (93.39%) levels, confirmed by histopathology.
Conclusions:
- The nasal ISPCLT formulation effectively enhances Candesartan's bioavailability and cardioprotective efficacy.
- This novel delivery system offers potential for lower dosages, improved patient adherence, and reduced adverse effects in managing cardiotoxicity.
- Nasal ISPCLT represents a promising strategy for advanced cardiotoxicity management.
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