PEGylated Liposomes Incorporated with Nonionic Surfactants as an Apomorphine Delivery System Targeting the Brain: In Vitro Release and In Vivo Real-time Imaging

Shu-Hui      Hsu; Saleh      A. Al-Suwayeh; Chih-Chieh      Chen; Chen-Hsien      Chi; Jia-You      Fang

Abstract

The clinical application of apomorphine, a dopamine receptor agonist for treating Parkinsons disease, is limited by its instability and the need for frequent injections. In the present work, apomorphine was encapsulated within liposomes to protect it from degradation and enhance the permeability across the blood-brain barrier (BBB). Stearylamine was used to produce a positive surface charge for the liposomes. The liposomal systems with different compositions were characterized by the mean size, zeta potential, drug encapsulation percentage, stability, and in vitro release characteristics. PEGylated liposomes and liposomes incorporating Brij 78 showed a size of 130~160 nm. When Tween 80 was added to the liposomes, the vesicle size increased to > 260 nm. Apomorphine was successfully entrapped by liposomes with an encapsulation percentage of > 70%, with the systems containing Brij 78 showing the highest level of 99%. The loading of apomorphine into liposomes resulted in slower release behavior compared to the drug in an aqueous solution. In comparison to free drug, apomorphine in PEGylated liposomes exhibited greater stability in plasma. The in vivo brain uptake of PEGylated liposomes after an intravenous bolus injection into rats was monitored by in vivo real-time bioluminescence imaging for 1 h. The results showed that the uptake of PEGylated liposomes into the brain was rapid and prolonged. PEGylated liposomes may offer a promising strategy for targeting apomorphine to the brain. This opens up new opportunities for treating Parkinsons disease.

Keywords: Apomorphine, PEGylated liposomes, blood-brain barrier, brain targeting, drug delivery systems, Nonionic Surfactants, Real-time Imaging, Parkinson's disease