Oromucosal Alginate Films with Zein Nanoparticles as a Novel Delivery System for Digoxin.

Daniela A Rodrigues,Paula Coutinho,Sónia P Miguel,Jorge Loureiro,Maximiano Ribeiro,Fátima Roque

doi:10.3390/pharmaceutics13122030

Daniela A Rodrigues, Paula Coutinho + Show 4 more

Open Access

https://doi.org/10.3390/pharmaceutics13122030

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Abstract

Digoxin is a hydrophobic drug used for the treatment of heart failure that possesses a narrow therapeutic index, which raises safety concerns for toxicity. This is of utmost relevance in specific populations, such as the elderly. This study aimed to demonstrate the potential of the sodium alginate films as buccal drug delivery system containing zein nanoparticles incorporated with digoxin to reduce the number of doses, facilitating the administration with a quick onset of action. The film was prepared using the solvent casting method, whereas nanoparticles by the nanoprecipitation method. The nanoparticles incorporated with digoxin (0.25 mg/mL) exhibited a mean size of 87.20 ± 0.88 nm, a polydispersity index of 0.23 ± 0.00, and a zeta potential of 21.23 ± 0.07 mV. Digoxin was successfully encapsulated into zein nanoparticles with an encapsulation efficiency of 91% (±0.00). Films with/without glycerol and with different concentrations of ethanol were produced. The sodium alginate (SA) films with 10% ethanol demonstrated good performance for swelling (maximum of 1474%) and mechanical properties, with a mean tensile strength of 0.40 ± 0.04 MPa and an elongation at break of 27.85% (±0.58), compatible with drug delivery application into the buccal mucosa. The current study suggests that SA films with digoxin-loaded zein nanoparticles can be an effective alternative to the dosage forms available on the market for digoxin administration.

Highlights

Heart failure is a pathological condition with an estimated worldwide prevalence of64.34 million cases representing the most significant burden after 60 years of age [1,2]
Sodium chloride 99.5% was obtained from Honeywell Fluka (Charlotte, NC, USA), potassium phosphate monobasic and sodium phosphate dibasic and High-Performance Liquid Chromatography (HPLC)-gradient grade acetonitrile 99.9% were obtained from VWR Chemicals (Radnor, PA, USA)
EtOH10 film containing ZnD × 0.25 nanoparticles was successfullyprepared prepared by by incorporating incorporating drug drug nanosuspensions nanosuspensions with with mucoadhesive mucoadhesive films films successfully mainly composed of sodium alginate (SA), which provides a new route of transforming nanosuspensions mainly composed of SA, which provides a new route of transforming nanosuspensions of of poorly water-soluble drugs as digoxin) solid dosage, to the poorly water-soluble drugs (such(such as digoxin) into ainto solida dosage, which which due to due the bioadbioadhesive behavior, reduced the number of administrations

Summary

Introduction

Heart failure is a pathological condition with an estimated worldwide prevalence of64.34 million cases representing the most significant burden after 60 years of age [1,2]. It is one of the most used drugs to improve symptoms and reduce hospitalization in patients with heart failure and atrial fibrillation [4] These conditions are highly prevalent in older adults [5]; digoxin is a widely prescribed drug at this age group [3,6]. This drug has a narrow therapeutic index, wide individual variability in dosage requirements, and complex metabolic pathways, which raises concern since digitalis toxicity is a medical emergency but can be lethal [7]. The older patient’s high sensitivity to glycosides and consequent risk of intoxication [8] highlights the need of developing new delivery systems for improving safety

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