Thiomer coated solid lipid nanoparticles for the enhanced oral bioavailability of tacrolimus: in-vitro and in-vivo evaluation

Abstract

The study was designed to enhance the oral bioavailability of tacrolimus, a BCS-II drug, extensively used in organ transplants to avoid tissue rejection. For this purpose, thiomer coated tacrolimus-loaded solid lipid nanoparticles (TC-SLNs-Tac) were prepared using beeswax as solid lipid, Tween 80 as surfactant, and soy lecithin as co-surfactant via high-pressure homogenization and emulsion congealing technique. Out of several trials prepared, the optimized SLNs formulation was further coated with thiolated chitosan (TCS) to produce TC-SLNs-Tac having a particle size of 214 ± 11 nm, the zeta potential of +31 meV, and spherical morphology. The TC-SLNs-Tac exhibited the highest mucoadhesion, controlled swelling, and cumulative release of 63.63% in 24 h. The ex-vivo permeation enhancement studies indicated that TC-SLNs-Tac was able to enhance the apparent permeability (P-app) by 4.35-fold and in-vivo oral bioavailability studies indicated a 4.73-fold enhanced oral bioavailability as compared to that of Tac only. The results provide the proof of concept of using thiomer-coated solid lipid nanoparticles as a potential candidate to enhance the oral bioavailability of Tac.