PEGylated Tween 80-functionalized chitosan-lipidic nano-vesicular hybrids for heightening nose-to-brain delivery and bioavailability of metoclopramide

• Published in: Drug delivery 2023-12, Vol.30 (1), p.2189112-2189112
• Main Authors: Al-Zuhairy, Saeed A. S., Teaima, Mahmoud H., Shoman, Nabil A., Elasaly, Mohamed, El-Nabarawi, Mohamed A., El-Sawy, Hossam S.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Bioavailability; Biological Availability; Brain - metabolism; Chitosan - metabolism; Drug Carriers - metabolism; Drug Delivery Systems; Lipidic-based nanovesicles; Lipids; Metoclopramide - metabolism; nose-to-brain delivery; optimization; PEGylation; Polysorbates; Rats; Rats, Sprague-Dawley; Tween 80 functionalization
• ISSN: 1071-7544; 1521-0464
• DOI: 10.1080/10717544.2023.2189112

A PEGylated Tween 80-functionalized chitosan-lipidic (PEG-T-Chito-Lip) nano-vesicular hybrid was developed for intranasal administration as an alternative delivery route to help improve the poor oral bioavailability of BCS class-III model/antiemetic (metoclopramide hydrochloride; MTC). The influence of varying levels of chitosan, cholesterol, PEG 600, and Tween 80 on the stability/release parameters of the formulated nanovesicles was optimized using Draper-Lin Design. Two optimized formulations (Opti-Max and Opti-Min) with both maximized and minimized MTC-release goals, were predicted, characterized, and proved their vesicular outline via light/electron microscopy, along with the mutual prompt/extended in-vitro release patterns. The dual-optimized MTC-loaded PEG-T-Chito-Lip nanovesicles were loaded in intranasal in-situ gel (ISG) and further underwent in-vivo pharmacokinetics/nose-to-brain delivery valuation on Sprague-Dawley rats. The absorption profiles in plasma (plasma-AUC 0-∞ ) of the intranasal dual-optimized MTC-loaded nano-vesicular ISG formulation in pretreated rats were 2.95-fold and 1.64-fold more than rats pretreated with orally administered MTC and intranasally administered raw MTC-loaded ISG formulation, respectively. Interestingly, the brain-AUC 0-∞ of the intranasal dual-optimized MTC-loaded ISG was 10 and 3 times more than brain-AUC 0-∞ of the MTC-oral tablet and the intranasal raw MTC-loaded ISG, respectively. It was also revealed that the intranasal dual-optimized ISG significantly had the lowest liver-AUC 0-∞ (862.19 ng.g −1 .h −1 ) versus the MTC-oral tablet (5732.17 ng.g −1 .h −1 ) and the intranasal raw MTC-loaded ISG (1799.69 ng.g −1 .h −1 ). The brain/blood ratio profile for the intranasal dual-optimized ISG was significantly enhanced over all other MTC formulations (P