Micro-Nano formulation of bile-gut delivery: rheological, stability and cell survival, basal and maximum respiration studies

Susbin Raj Wagle,Bozica Kovacevic,Hani Al-Salami,Daniel Walker,Ahmed Gedawy,Momir Mikov,Armin Mooranian,Svetlana Golocorbin-Kon

doi:10.1038/s41598-020-64355-z

Susbin Raj Wagle, Bozica Kovacevic + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-64355-z

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Journal: Scientific Reports	Publication Date: May 7, 2020
Citations: 33	License type: open-access

Affiliation: Curtin University, University of Novi Sad

Abstract

Probucol (PB) is a drug that exhibits significant hydrophobicity and substantial intra and inter individual variability in oral absorption, with a miniature bioavailability and complex three compartmental pharmacokinetic modelling due to its high lipid affinity, low stability and high octanol to water partition coefficient. Multiple attempts to formulate PB have not produced satisfactory stable matrices, drug-release profile or rheological flow properties for optimum manufacturing conditions, and with positive and none toxic biological effects. Lithocholic acid (LCA) has recently shown to optimise formulation and cell uptake of drugs. Hence, the aim of this study was to design new PB delivery system, using LCA, and examine its morphology, rheology, stability, and cellular effects. PB was formulated with LCA and sodium alginate (PB-LCA-SA) using various microencapsulation methodologies, and best formulation was investigated in vitro and ex vivo. Using our Ionic Gelation Vibrational Jet flow technology, PB-LCA-SA microcapsules showed good stability and significantly enhanced cell viability, cellular respiration, and reduced inflammation suggesting potential LCA applications in PB delivery and biological effects.

Highlights

Probucol (PB) is a drug that exhibits significant hydrophobicity and substantial intra and inter individual variability in oral absorption, with a miniature bioavailability and complex three compartmental pharmacokinetic modelling due to its high lipid affinity, low stability and high octanol to water partition coefficient
Insulin treatment is widely used in diabetes therapy, with all type 1 diabetes (T1D) patients, and in type 2 diabetes (T2D) more than one-third of T2D patients using insulin
One of the common symptoms associated with T2D development and progression is chronic inflammation of β-cells as well as high levels of low-density lipoproteins (LDL), free radicals and oxidants, which have been connected to exacerbation and worsening of diabetes-associated complications[21]

Summary

Introduction

Probucol (PB) is a drug that exhibits significant hydrophobicity and substantial intra and inter individual variability in oral absorption, with a miniature bioavailability and complex three compartmental pharmacokinetic modelling due to its high lipid affinity, low stability and high octanol to water partition coefficient. Published studies have shown that significant inflammation and damage of pancreatic β-cell plays a major role in diabetes and cardiovascular disease development and progression, since β-cells have limited defence against free radicals, oxidants and LDL-associated cellular toxicity[24,25]. In order to overcome challenges in probucol oral uptake in its current dosage form, new oral delivery matrices using cutting-edge technologies are needed. Such technologies can include microencapsulation with new excipients, that have demonstrated powerful oral targeted delivery, permeation enhancement properties and substantial consistent release profiles[6,28]

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