Cytotoxicity and bioavailability assessment from micellar system based Thiamine-Phospholipid complexes

Abstract

Poor absorption (3–5 %) of thiamine hydrochloride (TH), is primarily concerned with impaired permeability across intestinal mucosa. To modulate the permeability of TH, a phospholipid (PL) interaction-based hydrophobic complex of thiamine was investigated. Using the solvent evaporation approach, thiamine-phospholipid complexes (TPCs) were prepared between free bases of thiamine and PLs in the weight ratio (1:1, 1:2, and 2:1) and characterized using FTIR, spectrophotometry, XRD, and conductometric methods. Electrical conductivity and partition coefficient studies demonstrated that TPCs were hydrophobic transformations formed via PL interaction with a free thiamine base. TPCs were embedded into the micellar system (Tween20/Ethanol), characterized by electrical conductivities and zeta-sizing studies, and exploited in its micellar delivery system design. TPC 1:1 & 1:2 had much lower conductivity than TH and its physical mixture (TH/PL) in the Tween20/Ethanol environment diluted with an aqueous phase. The average size of micellar systems loaded with TPC (10 % w/w) was within the range of 12–25 nm, and conductivity was in the range of 122-130µS/cm. In vitro release characterization from complexes and their micellar systems in HCl 1.2, phosphate buffer (PB) 6.8, and bidistilled water showed a delayed release pattern. TPC modulated the intestinal permeability of thiamine as revealed from ex vivo studies. TPC (1:1) and its micellar system produced significant differences in drug permeability (p < 0.001) compared to TH and physical mixture. Pharmacokinetic assessment of the micellar system of complexes in Wistar rats showed that the TPC (1:1) loaded micellar system produced a 2.4-fold enhancement of AUC(0−24) over (TH) followed by oral administration. Assessment of cell viability in mouse fibroblast cell line (L929) culture showed that TPC or micellar system did not inhibit cell growth and was safe at various concentration levels. TPc complexes developed using phospholipid complexation yield hydrophobic transformation in TH and their micellar system-based delivery modulates the intestinal permeability and bioavailability enhancement.