Dopamine supplementations in the brain alleviates the neurological symptoms associated with the Parkinson’s disease, but several difficulties hamper its oral or peripheral administration for clinical uses: (i) inability to cross the blood brain barrier, (ii) induction of dangerous unwanted effects in peripheral tissues, (iii) extensive hepatic metabolism when orally administered. The enhancement of dopamine stability in physiologic environments and its brain targeting appear therefore useful and a challenging aspect in formulation development. We propose a new study concerning the preparation and characterization of solid lipid microparticles based on tristearin as sustained delivery system for dopamine. The microparticles were produced by the conventional hot emulsion technique. The synthesis of a new valeroyl ester of dopamine (3,4-O-divaleroyl-dopamine, DVD) was necessary to obtain its encapsulation in the microparticles. DVD appeared totally hydrolized to dopamine in human plasma within 40 seconds. The amount of encapsulated DVD in microparticles was 2.67 1.2%. The mean diameter of particles was 14.2 4.8 µm. The DVD release from microparticles was characterized by an initial burst of 20% of incorporated prodrug and a continuous slow release thereafter. The microparticles were found able to stabilize DVD in its solid form. We have finally demonstrated that DVD encapsulated in the microparticles degraded in human plasma with a markedly reduced rate in comparison with free prodrug. The DVD loaded microparticles appear therefore a promising system for dopamine uptake in the brain, following the nasal administration.
Solid lipid microparticles for the stability enhancement of a dopamine prodrug
DALPIAZ, Alessandro;CACCIARI, Barbara;MEZZENA, Matteo;STRADA, Mariangela;SCALIA, Santo
2009
Abstract
Dopamine supplementations in the brain alleviates the neurological symptoms associated with the Parkinson’s disease, but several difficulties hamper its oral or peripheral administration for clinical uses: (i) inability to cross the blood brain barrier, (ii) induction of dangerous unwanted effects in peripheral tissues, (iii) extensive hepatic metabolism when orally administered. The enhancement of dopamine stability in physiologic environments and its brain targeting appear therefore useful and a challenging aspect in formulation development. We propose a new study concerning the preparation and characterization of solid lipid microparticles based on tristearin as sustained delivery system for dopamine. The microparticles were produced by the conventional hot emulsion technique. The synthesis of a new valeroyl ester of dopamine (3,4-O-divaleroyl-dopamine, DVD) was necessary to obtain its encapsulation in the microparticles. DVD appeared totally hydrolized to dopamine in human plasma within 40 seconds. The amount of encapsulated DVD in microparticles was 2.67 1.2%. The mean diameter of particles was 14.2 4.8 µm. The DVD release from microparticles was characterized by an initial burst of 20% of incorporated prodrug and a continuous slow release thereafter. The microparticles were found able to stabilize DVD in its solid form. We have finally demonstrated that DVD encapsulated in the microparticles degraded in human plasma with a markedly reduced rate in comparison with free prodrug. The DVD loaded microparticles appear therefore a promising system for dopamine uptake in the brain, following the nasal administration.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
