Version 1
: Received: 27 September 2024 / Approved: 29 September 2024 / Online: 30 September 2024 (10:43:28 CEST)
How to cite:
Adwan, S.; Obeidi, T.; Al-Akayleh, F. In Situ Gel-Embedded Chitosan Nanoparticles for Nasal Delivery of Imipramine Hydrochloride: Optimization and Controlled Release Evaluation. Preprints2024, 2024092345. https://doi.org/10.20944/preprints202409.2345.v1
Adwan, S.; Obeidi, T.; Al-Akayleh, F. In Situ Gel-Embedded Chitosan Nanoparticles for Nasal Delivery of Imipramine Hydrochloride: Optimization and Controlled Release Evaluation. Preprints 2024, 2024092345. https://doi.org/10.20944/preprints202409.2345.v1
Adwan, S.; Obeidi, T.; Al-Akayleh, F. In Situ Gel-Embedded Chitosan Nanoparticles for Nasal Delivery of Imipramine Hydrochloride: Optimization and Controlled Release Evaluation. Preprints2024, 2024092345. https://doi.org/10.20944/preprints202409.2345.v1
APA Style
Adwan, S., Obeidi, T., & Al-Akayleh, F. (2024). In Situ Gel-Embedded Chitosan Nanoparticles for Nasal Delivery of Imipramine Hydrochloride: Optimization and Controlled Release Evaluation. Preprints. https://doi.org/10.20944/preprints202409.2345.v1
Chicago/Turabian Style
Adwan, S., Teiba Obeidi and Faisal Al-Akayleh. 2024 "In Situ Gel-Embedded Chitosan Nanoparticles for Nasal Delivery of Imipramine Hydrochloride: Optimization and Controlled Release Evaluation" Preprints. https://doi.org/10.20944/preprints202409.2345.v1
Abstract
Imipramine hydrochloride (IMP), a tricyclic antidepressant used for major depression, enuresis, and neuropathic pain, is limited by gastrointestinal complications, low oral bioavailability (44%), and complex dosing requirements. This study aimed to explore a novel non-invasive nasal delivery system using chitosan nanoparticles (Cs NPs) embedded in an in situ gel to address the limitations of oral IMP administration. Cs NPs loaded with IMP were synthesized via ionic gelation and assessed for precision in drug concentration using a validated HPLC method. The particles were integrated into a thermoresponsive polymer, Pluronic F127, to form an in situ gel suitable for nasal administration. The formulation was characterized for gelation temperature, duration, viscosity, mucoadhesive strength, and overall gel robustness. Drug release kinetics and the controlled release mechanism were studied using ex vivo permeation tests with Franz diffusion cells and nasal sheep mucosa. The optimized nanoparticle formulation (F4-50) exhibited a consistent PS of 141.7±2.2 nm, a ZP of 16.79±2.1 mV, and a high encapsulation efficiency of 67.71±1.9%. The selected in situ gel formulation, F4-50-P1, demonstrated a gelation temperature of 33.6±0.94°C and a rapid gelation time of 48.1±0.7 seconds. Transform-attenuated total reflectance infrared spectroscopy (ATR-IR) confirmed the compatibility and effective encapsulation of IMP within the formulation. The release profile of F4-50 included an initial burst release followed by a sustained release phase, with F4-50-P1 showing improved control over the burst release. The flux rates were 0.50±0.01 mg/cm²/h for F4-50 and 0.33±0.06 mg/cm²/h for F4-50-P1, indicating effective permeation. The developed chitosan nanoparticle-based in situ gel formulation provides a promising approach for the controlled release of IMP, enhancing therapeutic efficacy and patient compliance while mitigating the disadvantages associated with oral delivery.
Keywords
Chitosan; Pluronic; Nanoparticles; In situ gel; Nasal drug delivery; Imipramine
Subject
Medicine and Pharmacology, Pharmacy
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
