Starch-coated magnetic liposomes as an inhalable carrier for accumulation of fasudil in the pulmonary vasculature.
In this study, we tested the feasibility of magnetic liposomes as a carrier for pulmonary preferential accumulation of fasudil, an investigational drug for the treatment of pulmonary arterial hypertension (PAH). To develop an optimal inhalable formulation, various magnetic liposomes were prepared and characterized for physicochemical properties, storage stability and in vitro release profiles. Select formulations were evaluated for uptake by pulmonary arterial smooth muscle cells (PASMCs) - target cells - using fluorescence microscopy and HPLC. The efficacy of the magnetic liposomes in reducing hyperplasia was tested in 5-HT-induced proliferated PASMCs. The drug absorption profiles upon intratracheal administration were monitored in healthy rats. Optimized spherical liposomes - with mean size of 170 nm, zeta potential of -35mV and entrapment efficiency of 85% - exhibited an 80% cumulative drug release over 120 h. Fluorescence microscopic study revealed an enhanced uptake of liposomes by PASMCs under an applied magnetic field: the uptake was 3-fold greater compared with that observed in the absence of magnetic field. PASMC proliferation was reduced by 40% under the influence of the magnetic field. Optimized liposomes appeared to be safe when incubated with PASMCs and bronchial epithelial cells. Compared with plain fasudil, intratracheal magnetic liposomes containing fasudil extended the half-life and area under the curve by 27- and 14-fold, respectively. Magnetic-liposomes could be a viable delivery system for site-specific treatment of PAH.
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Street, Amarillo, TX 79106, United States.
Kamrun
K
Nahar
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Street, Amarillo, TX 79106, United States.
Shahriar
S
Absar
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Street, Amarillo, TX 79106, United States.
Brijeshkumar
B
Patel
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Street, Amarillo, TX 79106, United States. Electronic address: fakhrul.ahsan@ttuhsc.edu.
Fakhrul
F
Ahsan
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000280:Administration, Inhalation; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes; D008168:Lung / Q000098:blood supply* / Q000378:metabolism*; D060328:Magnetic Phenomena; D051381:Rats; D017207:Rats, Sprague-Dawley; D013213:Starch / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*
D004337:Drug Carriers; D008081:Liposomes; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013213:Starch; C049347:fasudil
Lipid-based formulations; Magnetic liposomes; Pulmonary arterial hypertension (PAH); Pulmonary delivery