Improved pharmacokinetic parameters and reduced tissue distribution of prodrug of Triamcinolone acetonide in lipid nanospheres- A preliminary investigation.

Abstract

Objective: In the current research work, we synthesized Triamcinolone acetonide palmitate (TAP), a lipophilic prodrug of TA and formulated it into lipid nanospheres (TAP-LN) to improve pharmacokinetics and tissue distribution on intravenous administration.

Significance: Triamcinolone acetonide (TA) is a parenteral glucocorticoid used to treat several inflammatory disorders. It has a short plasma half-life (2-3 h) and its parenteral administration causes severe side effects.

Methods: Tap-LNs were composed of soy lecithin, soybean oil, Miglyol 812N as a lipid phase and poloxamer 188 and glycerol in distilled water as an aqueous phase. The coarse emulsion was subjected to probe sonication followed by a microfluidizer by applying 20,000 psi pressure with 10 cycles. Similarly, TAP-lipid microspheres (TAP-LM) were prepared for comparative study without microfluidization.

Results: The optimized TAP-LN exhibited a size of 106.8nm, zeta potential of -45.7mV, and entrapment efficiency of 82.35%. A pharmacokinetic study showed that in rats, TAP-LN exhibited a 4.5-fold plasma concentration and 10-fold AUC0-t than TAP-lipid microspheres (TAP-LM). The slow clearance of TAP-LN could be associated with lower uptake by eliminating organs that eventually increased the residence time. In the spleen, TAP-LM concentrations were higher than TAP-LN; TAP-LN could not be detected in the liver, unlike TAP-LM, attributing to the carboxylesterase lipase, the metabolizing enzyme responsible for the conversion of TAP to TA. Conclusions: Thus, TAP nanospheres showed improved pharmacokinetic parameters and reduced tissue distribution, which would benefit the intravenous treatment of this glucocorticoid.