Hybrid Nanobeads for Oral Indomethacin Delivery.

Gustavo Henrique Rodrigues da Silva,Leandro Santana Soares da Silva,Lígia Nunes de Morais Ribeiro,Gabriela Ribeiro da Silva,Eneida de Paula,Márcia Cristina Breitkreitz,Belchiolina Beatriz Fonseca,Ludmilla David de Moura,Flávia Monique Rocha Bonetti

doi:10.3390/pharmaceutics14030583

Gustavo Henrique Rodrigues da Silva, Leandro Santana Soares da Silva + Show 7 more

Open Access

https://doi.org/10.3390/pharmaceutics14030583

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Abstract

The oral administration of the anti-inflammatory indomethacin (INDO) causes severe gastrointestinal side effects, which are intensified in chronic inflammatory conditions when a continuous treatment is mandatory. The development of hybrid delivery systems associates the benefits of different (nano) carriers in a single system, designed to improve the efficacy and/or minimize the toxicity of drugs. This work describes the preparation of hybrid nanobeads composed of nanostructured lipid carriers (NLC) loading INDO (2%; w/v) and chitosan, coated by xanthan. NLC formulations were monitored in a long-term stability study (25 °C). After one year, they showed suitable physicochemical properties (size < 250 nm, polydispersity < 0.2, zeta potential of −30 mV and spherical morphology) and an INDO encapsulation efficiency of 99%. The hybrid (lipid-biopolymers) nanobeads exhibited excellent compatibility between the biomaterials, as revealed by structural and thermodynamic properties, monodisperse size distribution, desirable in vitro water uptake and prolonged in vitro INDO release (26 h). The in vivo safety of hybrid nanobeads was confirmed by the chicken embryo (CE) toxicity test, considering the embryos viability, weights of CE and annexes and changes in the biochemical markers. The results point out a safe gastro-resistant pharmaceutical form for further efficacy assays.

Highlights

Indomethacin (INDO) is a non-steroidal anti-inflammatory (NSAID) agent widely used for pain, fever and inflammation control through oral administration [1]
The shelf life of the Nanostructured lipid carriers (NLC) formulations with or whitout 2% INDO were assessed through size, polydispersity index (PDI), Zeta potential, pH and visual inspection monitoring for 1 year at 25 ◦ C (Figure 1)
This is probably due to the different lipid–biopolymer barriers and the nanoencapsulation that decreased INDO toxicity in chicken embryo (CE) together with the biopolymer protective effect. Such evidence suggests that the nanobead was the least toxic treatment for CE, not causing significant deaths, macroscopic damages or biochemical markers alterations to CE. These results strongly suggested that xanthan gum (XAN)@CHT/NLC-INDO was effective to prolong the INDO release profile, exhibited gastro-resistant properties and decreased the drug toxicity, as claimed

Summary

Introduction

Indomethacin (INDO) is a non-steroidal anti-inflammatory (NSAID) agent widely used for pain, fever and inflammation control through oral administration [1]. Severe side effects in the gastrointestinal system (e.g., nausea, indigestion, vomit, diarrhea and abdominal ache) are associated to the oral administration, due to the first-pass metabolism. These effects are exacerbated in chronic diseases, in which an extended treatment is required [2]. Colloidal drug delivery systems (DDS) with optimized therapeutic actions should decrease side effects by the sustained release of the loaded drugs [4]. NLC formulations loading different anti-inflammatory compounds for multi-application and administration routes have been successfully reported [6–8].

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