Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Oral Delivery of Posaconazole-Loaded Phospholipid-Based Nanoformulation: Preparation and Optimization Using Design of Experiments, Machine Learning, and Topsis Publisher Pubmed



Bayat F1 ; Dadashzadeh S1 ; Aboofazeli R1, 2 ; Torshabi M3 ; Baghi AH4 ; Tamiji Z5 ; Haeri A1, 2
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Department of Dental Biomaterials, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Department of Industrial Engineering and Management Systems, Amirkabir University of Technology, Tehran, Iran
  5. 5. Department of Chemometrics, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

Source: International Journal of Pharmaceutics Published:2024


Abstract

Phospholipid-based nanosystems show promising potentials for oral administration of hydrophobic drugs. The study introduced a novel approach to optimize posaconazole-loaded phospholipid-based nanoformulation using the design of experiments, machine learning, and Technique for Order of Preference by Similarity to the Ideal Solution. These approaches were used to investigate the impact of various variables on the encapsulation efficiency (EE), particle size, and polydispersity index (PDI). The optimized formulation, with %EE of ∼ 74 %, demonstrated a particle size and PDI of 107.7 nm and 0.174, respectively. The oral pharmacokinetic profiles of the posaconazole suspension, empty nanoformulation + drug suspension, and drug-loaded nanoformulation were evaluated. The nanoformulation significantly increased maximum plasma concentration and the area under the drug plasma concentration–time curve (∼3.9- and 6.2-fold, respectively) and could be administered without regard to meals. MTT and histopathological examinations were carried out to evaluate the safety of the nanoformulation and results exhibited no significant toxicity. Lymphatic transport was found to be the main mechanism of oral delivery. Caco-2 cell studies demonstrated that the mechanism of delivery was not based on an increase in cellular uptake. Our study represents a promising strategy for the development of phospholipid-based nanoformulations as efficient and safe oral delivery systems. © 2024 Elsevier B.V.
Experts (# of related papers)