Site-specific microinjection of liposomes into the brain for local infusion of a short-lived peptide.
The short-lived peptide, angiotensin-(1-7) (Ang-(1-7)), was encapsulated in different liposome preparations, in order to evaluate the influence of membrane fluidity, membrane surface, liposome size and dose of peptide on the cardiovascular effects of the encapsulated peptide at a specific site of the brain. These preparations were microinjected unilaterally into the rostral ventrolateral medulla (RVLM) of Wistar rats, and mean arterial blood pressure (MAP) and heart rate (HR) were registered by telemetry. Pegylated, rigid and calibrated (200 nm) liposomes, containing 50 ng of Ang-(1-7), elicited a significant increase of MAP for at least 7 days, in contrast to empty liposomes or non-pegylated liposomes. When a two-fold higher peptide dose was employed or when pegylated liposomes were used in the fluid state or uncalibrated, less pronounced pressor effects were observed. These data show that the cardiovascular responses to the microinjection of Ang-(1-7)-containing liposomes into the RVLM can be modulated through the manipulation of liposome characteristics. These results can be explained by the influence of liposome characteristics on the flux of peptide release. It is expected that this new method will encounter numerous applications in the study of the chronic actions of short-lived bioactive peptides in specific sites of the brain.
Faculdade de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto, 35400-000 Ouro Prêto, MG, Brazil.
Neila M
NM
Silva-Barcellos
Sordaini
S
Caligiorne
Robson A S
RA
dos Santos
Frédéric
F
Frézard
D000803:Angiotensin I / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers; D006339:Heart Rate / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D008560:Membrane Fluidity; D008566:Membranes / Q000737:chemistry; D008845:Microinjections; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
D004337:Drug Carriers; D008081:Liposomes; D010446:Peptide Fragments; D010455:Peptides; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D000803:Angiotensin I; C118790:angiotensin I (1-7)