Potential dopamine prodrug-loaded liposomes: preparation, characterization, and in vitro stability studies.
Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of the blood-brain barrier (BBB). Condensation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. To improve the bioavailability of the dopamine prodrug, 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DOPH), it was encapsulated in unilamellar liposomes of dimiristoylphosphatidylcholine (DMPC) and cholesterol. Vesicles were characterized by dynamic light scattering in order to evaluate their dimensions and vesicle stability, by zeta-potential measurements, by means of electronic microscopy after freeze-fracture and differential scanning calorimetry. The influence of vesicle composition on DOPH chemical and enzymatic stability was also evaluated. The formulated liposome suspensions were found to be stable, monodisperse systems with a negative zeta potential. From the obtained results, it is possible to conclude that, in studied samples, DOPH inclusion in liposomes offers the possibility of preventing photodegradation and of enhancing in vitro plasma stability. These studies suggest the potential of these formulations as a method to prevent DOPH chemical degradation and enzymatic metabolism.
Carafa
Maria
M
Department Chimica e Tecnologie del Farmaco, University of Rome Sapienza, Rome, Italy.
Marianecci
Carlotta
C
Di Marzio
Luisa
L
De Caro
Viviana
V
Giandalia
Giulia
G
Giannola
Libero Italo
LI
Santucci
Eleonora
E
D002152:Calorimetry, Differential Scanning; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004298:Dopamine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D008027:Light; D008081:Liposomes / Q000737:chemistry / Q000302:isolation & purification*; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D012542:Scattering, Radiation
C553723:2-amino-N-(2-(3,4-dihydroxyphenyl)ethyl)-3-phenylpropionamide; D008081:Liposomes; D011355:Prodrugs; D010649:Phenylalanine; D004134:Dimyristoylphosphatidylcholine; D004298:Dopamine