PEGylated Tween 80-functionalized Chitosan-lipidic Nano-vesicular Hybrids for Heightening Nose-to-brain Delivery and Bioavailability of Metoclopramide

Overview

Journal Drug Deliv

Specialty Pharmacology

Date 2023 Mar 14

PMID 36916128

Authors

Saeed A S Al-Zuhairy

Mahmoud H Teaima

Nabil A Shoman

Mohamed Elasaly

Mohamed A El-Nabarawi

Hossam S El-Sawy

Affiliations

Soon will be listed here.

Abstract

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 light/electron microscopy, along with the mutual prompt/extended release patterns. The dual-optimized MTC-loaded PEG-T-Chito-Lip nanovesicles were loaded in intranasal gel (ISG) and further underwent pharmacokinetics/nose-to-brain delivery valuation on Sprague-Dawley rats. The absorption profiles in plasma (plasma-AUC) 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 of the intranasal dual-optimized MTC-loaded ISG was 10 and 3 times more than brain-AUC 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 (862.19 ng.g.h) versus the MTC-oral tablet (5732.17 ng.g.h) and the intranasal raw MTC-loaded ISG (1799.69 ng.g.h). The brain/blood ratio profile for the intranasal dual-optimized ISG was significantly enhanced over all other MTC formulations (P < 0.05). Moreover, the 198.55% drug targeting efficiency, 75.26% nose-to-brain direct transport percentage, and 4.06 drug targeting index of the dual-optimized formulation were significantly higher than those of the raw MTC-loaded ISG formulation. The performance of the dual-optimized PEG-T-Chito-Lip nano-vesicular hybrids for intranasal administration evidenced MTC-improved bioavailability, circumvented hepatic metabolism, and enhanced brain targetability, with increased potentiality in heightening the convenience and compliance for patients.

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References

Lee A, Kuo B . Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2011; 5(5):653-662. PMC: 3027056. DOI: 10.1586/eem.10.41. View

Bayindir Z, Yuksel N . Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery. J Pharm Sci. 2009; 99(4):2049-60. DOI: 10.1002/jps.21944. View

Jonkman J, van der Boon W, Schoenmaker R, Holtkamp A . The absolute bioavailability of a new pediatric sustained release theophylline tablet, when given as whole or divided tablets. Int J Clin Pharmacol Ther Toxicol. 1984; 22(9):506-10. View

Waddad A, Abbad S, Yu F, Munyendo W, Wang J, Lv H . Formulation, characterization and pharmacokinetics of Morin hydrate niosomes prepared from various non-ionic surfactants. Int J Pharm. 2013; 456(2):446-58. DOI: 10.1016/j.ijpharm.2013.08.040. View

Gajra B, Dalwadi C, Patel R . Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using Box Behnken design. Daru. 2015; 23:3. PMC: 4312448. DOI: 10.1186/s40199-014-0087-0. View

Denora N, Trapani A, Laquintana V, Lopedota A, Trapani G . Recent advances in medicinal chemistry and pharmaceutical technology--strategies for drug delivery to the brain. Curr Top Med Chem. 2009; 9(2):182-96. DOI: 10.2174/156802609787521571. View

Chen S, Hanning S, Falconer J, Locke M, Wen J . Recent advances in non-ionic surfactant vesicles (niosomes): Fabrication, characterization, pharmaceutical and cosmetic applications. Eur J Pharm Biopharm. 2019; 144:18-39. DOI: 10.1016/j.ejpb.2019.08.015. View

Abaee A, Madadlou A . Niosome-loaded cold-set whey protein hydrogels. Food Chem. 2015; 196:106-13. DOI: 10.1016/j.foodchem.2015.09.037. View

Kassem M, El-Sawy H, Abd-Allah F, Abdelghany T, El-Say K . Maximizing the Therapeutic Efficacy of Imatinib Mesylate-Loaded Niosomes on Human Colon Adenocarcinoma Using Box-Behnken Design. J Pharm Sci. 2016; 106(1):111-122. DOI: 10.1016/j.xphs.2016.07.007. View

10.

Herrstedt J, Lindberg S, Petersen P . Prevention of Chemotherapy-Induced Nausea and Vomiting in the Older Patient: Optimizing Outcomes. Drugs Aging. 2021; 39(1):1-21. PMC: 8654643. DOI: 10.1007/s40266-021-00909-8. View

11.

Pardakhty A, Varshosaz J, Rouholamini A . In vitro study of polyoxyethylene alkyl ether niosomes for delivery of insulin. Int J Pharm. 2006; 328(2):130-41. DOI: 10.1016/j.ijpharm.2006.08.002. View

12.

Zaki N, Awad G, Mortada N, Abd ElHady S . Rapid-onset intranasal delivery of metoclopramide hydrochloride. Part I. Influence of formulation variables on drug absorption in anesthetized rats. Int J Pharm. 2006; 327(1-2):89-96. DOI: 10.1016/j.ijpharm.2006.07.040. View

13.

Mehta S, Jindal N . Formulation of Tyloxapol niosomes for encapsulation, stabilization and dissolution of anti-tubercular drugs. Colloids Surf B Biointerfaces. 2012; 101:434-41. DOI: 10.1016/j.colsurfb.2012.07.006. View

14.

Tian X, Liu F, Li Z, Lin Y, Liu H, Hu P . Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption. Front Pharmacol. 2019; 10:19. PMC: 6353801. DOI: 10.3389/fphar.2019.00019. View

15.

Ganger S, Schindowski K . Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa. Pharmaceutics. 2018; 10(3). PMC: 6161189. DOI: 10.3390/pharmaceutics10030116. View

16.

Abdulkarim M, Agullo N, Cattoz B, Griffiths P, Bernkop-Schnurch A, Borros S . Nanoparticle diffusion within intestinal mucus: Three-dimensional response analysis dissecting the impact of particle surface charge, size and heterogeneity across polyelectrolyte, pegylated and viral particles. Eur J Pharm Biopharm. 2015; 97(Pt A):230-8. DOI: 10.1016/j.ejpb.2015.01.023. View

17.

Zaki N, Awad G, Mortada N, Abd Elhady S . Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci. 2007; 32(4-5):296-307. DOI: 10.1016/j.ejps.2007.08.006. View

18.

Danhier F, Lecouturier N, Vroman B, Jerome C, Marchand-Brynaert J, Feron O . Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. J Control Release. 2008; 133(1):11-7. DOI: 10.1016/j.jconrel.2008.09.086. View

19.

Li Q, Li Z, Zeng W, Ge S, Lu H, Wu C . Proniosome-derived niosomes for tacrolimus topical ocular delivery: in vitro cornea permeation, ocular irritation, and in vivo anti-allograft rejection. Eur J Pharm Sci. 2014; 62:115-23. DOI: 10.1016/j.ejps.2014.05.020. View

20.

Marianecci C, Rinaldi F, Di Marzio L, Mastriota M, Pieretti S, Celia C . Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models. Int J Nanomedicine. 2014; 9:635-51. PMC: 3908944. DOI: 10.2147/IJN.S55066. View