Journal Article

Preparation and Characterization of a Novel Mucoadhesive Carvedilol Nanosponge: A Promising Platform for Buccal Anti-Hypertensive Delivery

Khafagy, El-Sayed, Ahmed, Mahgoub Mohamed, Almutairy, Bjad K., Alotaibi, Hadil Faris, Gad, Shadeed, Alshetaili, Abdullah, Alshahrani, Saad M., Sanad, Rania Abdel-Basset, Ghorab, Mamdouh Mostafa, Abu Lila, Amr S., Aldawsari, Mohammed F., Alalaiwe, Ahmed, Sallam, Nahed Mohamed, Al Saqr, Ahmed

2022

Overview

Carvedilol (CRV) is a non-selective third generation beta-blocker used to treat hypertension, congestive heart failure and angina pectoris. Oral administration of CRV showed poor bioavailability (25%), which might be ascribed to its extensive first-pass metabolism. Buccal delivery is known to boost drugs bioavailability. The aim of this study is to investigate the efficacy of bilosomes-based mucoadhesive carvedilol nanosponge for enhancing the oral bioavailability of CRV. The bilosomes were prepared, optimized and characterized for particle size, surface morphology, encapsulation efficiency and ex-vivo permeation studies. Then, the optimized formula was incorporated into a carboxymethyl cellulose/hydroxypropyl cellulose (CMC/HPC) composite mixture to obtain buccal nanosponge enriched with CRV bilosomes. The optimized bilosome formula (BLS9), showing minimum vesicle size, maximum entrapment, and highest cumulative in vitro release, exhibited a spherical shape with 217.2 nm in diameter, 87.13% entrapment efficiency, and sustained drug release for up to 24 h. In addition, ex-vivo drug permeation across sheep buccal mucosa revealed enhanced drug permeation with bilosomal formulations, compared to aqueous drug suspension. Consecutively, BLS9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain bilosomal nanosponge to enhance CRV buccal delivery. Morphological analysis of the prepared nanosponge revealed improved swelling with a porosity of 67.58%. The in vivo assessment of rats indicated that CRV-loaded nanosponge efficiently enhanced systolic/diastolic blood pressure, decreased elevated oxidative stress, improved lipid profile and exhibited a potent cardio-protective effect. Collectively, bilosomal nanosponge might represent a plausible nanovehicle for buccal delivery of CRV for effective management of hypertension.

• Publisher: MDPI AG,MDPI
• Subject: Angina pectoris / Antihypertensives / bilosomes / Bioavailability / buccal mucosa / Carboxymethyl cellulose / carvedilol / Cholesterol / Drug delivery systems / Drug dosages / Efficiency / Entrapment / Formulations / heart biomarkers / Hydroxypropyl cellulose / Hypertension / Lipids / Metabolism / Morphology / mucoadhesive nanosponge / Oral administration / Particle size / Penetration