Conception of nanosized hybrid liposome/poloxamer particles to thicken the interior core of liposomes and delay hydrophilic drug delivery

Abstract

Liposomes are nanocarriers composed of phospholipids, especially designed to potentially carry drugs. However, liposomes suffer in terms of leakage of small hydrophilic drugs. To control the release, a system with lipid shell and polymeric viscous core, namely Hybrid liposome/polymer inside (HLP_in), has been designed. For this purpose, we setup a syringe pump apparatus equipped with homemade tubing system. HLPin formulation consisting of poloxamer (5% w/v) was found to be optimal when produced at injection rates of 5 mL.min^-1. Then, we tend to characterize the HLP_in with DLS, TEM, TRPS, thermal analysis and densitometry in comparison with a polymer added after formation of the liposomes. The optimal formulation was evaluated for its stability and cytotoxicity. The selected conditions and composition resulted in nanocarriers which are highly reproducible with mono-disperse size distribution with an average size of 206 ± 4.8 nm and a polydispersity index of 0.15 ± 0.015. Densitometry and thermal analysis results confirmed the formation of HLP_in. Interestingly, HLP_in were stable over 2 months, produced no cytotoxicity and exhibited slow release of rhodamine and Doxorubicin in comparison to liposome formulation. Our homemade tubing system coupled with syringe pump apparatus achieved reproducible, precisely controlled production for the HLPin formulation which can be scale up.

Keywords: Gelliposomes; Hybrid liposome/polymer; Poloxamer; Rhodamine; Syringe pump.