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

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.

Pharmacological and Advanced Cell Respiration Effects, Enhanced by Toxic Human-Bile Nano-Pharmaceuticals of Probucol Cell-Targeting Formulations

“…The post-stability drug content was similar to fresh microcapsules, which proved that there was no significant loss of PB under these testing conditions from both microcapsules. This study is consistent with a previous study where the F1 and F2 microcapsules' physicochemical compatibility was analysed [39]. Differential scanning calorimetry (DSC) results showed that PB did not participate in a cross-linking reaction with LVSA and BA, and did not compromise thermal and chemical integrity during the microencapsulation process, which is further supported by the Fourier-transform infrared spectroscopy (FTIR) analysis [39].…”

“…The reduction in IFN-γ and enhancement in IL-10 that the PB-ULCA microcapsules showed, are expected to decrease cell apoptosis and support cell function, which is supported by bioenergetics analysis [81]. Previously published data have displayed that the anti-oxidant activity of BAs enhanced β-cell viability [39,[81][82][83].…”

“…Figure 5 A shows that the level of IFN-γ production was significantly higher in untreated cells (13.50 ± 0.90 pg/mL) ( p < 0.01), whereas the levels decreased in cells treated with microcapsules (F1 = 7.90 ± 1.4 pg/mL and F2 = 5.80 ± 1.30 pg/mL). The basic MTT assay was initially carried out to examine the cell biological activity and the results were consistent with IFN-γ levels [ 39 ]. Likewise, the expression of anti-inflammatory cytokine IL-10 was 3 ± 0.80 pg/mL in the control and increased considerably in the treated cells (F1 = 5.70 ± 0.85 pg/mL and F2 = 8.90 ± 0.72 pg/mL) ( p < 0.01) ( Figure 5 B).…”

“…Therefore, we hypothesized that using a more structurally stable, rigid and less soluble BA may improve PB release patterns, and promote the targeted delivery by increasing water permeation in microcapsules. Unconjugated lithocholic acid (ULCA) is a promising compound, endogenously produced in humans, and recently it was shown to possess formulation-stabilizing and anti-inflammatory effects [ 38 , 39 ]. Moreover, ULCA has substantially different chemical structure compared with other Bile acids (BAs), different hydrophilicity, and contrasting effects in vivo .…”

Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid

“…Previously, our studies have demonstrated that sodium alginate microcapsules significantly increase the brain uptake and associated neuroprotective effects of probucol-the highly lipophilic, antilipidemic drug [11]. Subsequent studies of ours confirmed that microencapsulation improves therapeutic efficiency of lipophilic drugs by protecting against degradation due to low stomach pH and efflux protein activity in the intestinal epithelium [12,13].…”