title: Development and evaluation of perfluorocarbon nanobubbles for apomorphine delivery.
abstract: Apomorphine is a dopamine receptor agonist for treating Parkinson's disease. However, its clinical application is limited by its instability and the need for frequent injections. The aim of the present work was to develop acoustically active perfluorocarbon nanobubbles (PNs) for encapsulation of both apomorphine HCl and base forms to circumvent these delivery problems. The PNs were prepared using coconut oil and perfluoropentane as the inner phase, which was emulsified by phospholipids and cholesterol. The morphology, size, zeta potential, and drug release of the PNs were characterized. The particle size ranged from 150 to 380 nm, with differences in the oil or perfluorocarbon ratio in the formulations. Atomic force microscopy confirmed oval- or raisin-shaped particles and a narrow size distribution of these systems (polydispersity index = 0.25-0.28). The stability experimental results indicated that PNs could protect apomorphine from degradation. Evaporation of the PNs at 37 degrees C was also limited. Apomorphine HCl and base in PNs showed retarded and sustained release profiles. Ultrasound imaging confirmed the echogenic activity of PNs developed in this study. The apomorphine HCl release by insonation at 1 MHz showed enhancements of two- to fourfold compared to the non-ultrasound group, illustrating a possible drug-targeting effect. On the contrary, apomorphine base showed a decreased release profile with ultrasound application. Apomorphine-loaded PNs showed promising stability and safety. They were successful in sustaining apomorphine delivery.
authors.affiliation: Cell Pharmacology Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Yin-Ku
authors.initials: YK
authors.lastname: Lin
authors.forename: Chen-Hsien
authors.initials: CH
authors.lastname: Chi
authors.forename: Tse-Hung
authors.initials: TH
authors.lastname: Huang
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001058:Apomorphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004563:Electrochemistry; D004912:Erythrocytes / Q000737:chemistry; D005466:Fluorocarbons / Q000737:chemistry*; D006207:Half-Life; D006461:Hemolysis; D006801:Humans; D007263:Infusions, Parenteral; D008081:Liposomes; D018625:Microscopy, Atomic Force; D053758:Nanoparticles; D010316:Particle Size; D013500:Surface Tension; D014465:Ultrasonics
chemical_list: D000978:Antiparkinson Agents; D005466:Fluorocarbons; D008081:Liposomes; D001058:Apomorphine