Controlled Delivery of Ondansetron from Lipid Carriers

Abstract

Postoperative nausea and vomiting (PONV) is one ofthe most common preoperative concerns. PONV usually leads to patient discomfort, delayeddischarge from the intensive care unit (ICU) or hospital,and increased medical costs. Moreover, severe vomitingmay result in dehydration, electrolyte imbalance, andacid–base disturbance.These concerns are also fornausea and vomiting associated with chemotherapy or radiotherapy. Various antiemetics, including anticholinergics and dopaminereceptor antagonists, have been studied with regardto their efficacy for the prevention and treatmentofPONV. However, these agents have been reportedto have adverse effects such as excessive sedation,hypotension, dysphoria, hallucinations, and extrapyramidalsigns. Selective5-HT3 receptor antagonists (ondansetron, granisetron, andtropisetron) are effective in PONV and chemotherapy‐ induced nausea and vomiting in cancerpatients. The half‐life of Ondansetron in plasma has been reported to be 3-4 hours.The shorter biological half‐life and frequent dosing inchemotherapy‐induced nausea and vomiting make it a good candidate for sustained release drug delivery system. The aim of the current work is to formulate stable ondansetron-loaded cubosomes for sustained intramuscular injection aiming to improve the patient compliance who may suffer from difficulty in swallowing the conventional oral tablets and also reduce hospitalization costs by shifting from the IV infusion of ondansetron to the sustained IM injections. Hence, different amphiphilic lipids were screened for their ability to form cubosomes. A full factorial design was then developed to prepare optimized ondansetron-loaded nanoparticles with tailored physical characteristics such as PS, PDI and EE% suitable for sustained Summary 219 intramuscular delivery. Optimized formulae were subjected to lyophilization and spray drying procedures to enhance their stability and shelf life. Finally, In vivo studies were conducted to investigate Ondansetron nanoparticles pharmacokinetics and tissue tolerance to the fabricated formulae.