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

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

Significance: Triamcinolone acetonide 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-LMs) were prepared for comparative study without microfluidization.

Results: The optimized TAP-LN exhibited a size of 106.8 nm, zeta potential of -45.7 mV, 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 AUC_0-t than TAP-LMs. 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.

Conclusion: Thus, TAP nanospheres showed improved pharmacokinetic parameters and reduced tissue distribution, which would benefit the intravenous treatment of this glucocorticoid.