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Permeability Profiles and Intestinal Toxicity Assessment of Hydrochlorothiazide and Its Inclusion Complex with
R Onnainty1, E M Schenfeld1, J P Petiti2
1Departamento de Farmacia, UNITEFA, CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba , Córdoba, X5000HUA, Argentina.
Molecular Pharmaceutics
|October 21, 2016
Summary
A new chitosan nanoparticle system for hydrochlorothiazide (HCT) reduces intestinal injury. This drug delivery system improves HCT intestinal permeability and lessens epithelial damage compared to free HCT.
Area of Science:
- Pharmacology
- Materials Science
- Gastroenterology
Background:
- Free hydrochlorothiazide (HCT) can cause intestinal mucosa injury and abnormal permeability.
- The Na+/K+-ATPase channel is implicated in HCT's intestinal effects.
- Chitosan nanoparticles (CS NPs) offer potential for controlled drug delivery.
Purpose of the Study:
- To develop and evaluate a novel chitosan nanoparticle-based drug delivery system for hydrochlorothiazide (HCT).
- To investigate the impact of this new system on intestinal permeability and epithelial integrity compared to free HCT.
- To explore the mechanism behind HCT-induced intestinal injury and how the nanoparticle system mitigates it.
Main Methods:
- Formulation of chitosan/hydrochlorothiazide:β-cyclodextrin inclusion complex nanoparticles (CS/HCT:βCD NPs).
- Assessment of intestinal permeability profiles for both free HCT and CS/HCT:βCD NPs.
- Evaluation of intestinal epithelial damage induced by free HCT and the nanoparticle system.
Main Results:
- CS/HCT:βCD NPs significantly ameliorated intestinal epithelial damage caused by HCT.
- Free HCT exhibited exponential intestinal permeability, while CS/HCT:βCD NPs showed linear permeability.
- The nanoparticle system demonstrated increased gastrointestinal retention and slower drug release.
Conclusions:
- The developed CS/HCT:βCD NPs act as an effective drug delivery system, reducing HCT-induced intestinal injury.
- The nanoparticle system's mechanism involves enhanced mucus adherence and controlled release, maintaining lower luminal drug levels.
- This novel delivery approach mitigates local intestinal toxicity associated with hydrochlorothiazide therapy.
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