Innovative lipid-based carriers containing cationic derivatives of polyisoprenoid alcohols augment the antihypertensive effectiveness of candesartan in spontaneously hypertensive rats
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
HYPERTENSION RESEARCH (25pkt w roku publikacji)
ISSN
0916-9636
EISSN
Wydawca
NATURE PUBLISHING GROUP
DOI
URL
Rok publikacji
2018
Numer zeszytu
4
Strony od-do
234-245
Numer tomu
41
Identyfikator DOI
Liczba arkuszy
1,00
Słowa kluczowe
en
AT(1) BLOCKADE
BLOOD-PRESSURE
RENAL-FUNCTION
DRUG-DELIVERY
NITRIC-OXIDE
NEPHROTOXICITY
BIOSYNTHESIS
BIOMARKERS
MEMBRANES
DOLICHOL
Streszczenia
Język
en
Treść
Novel lipid-based carriers, composed of cationic derivatives of polyisoprenoid alcohols (amino-prenols, APrens) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), were designed. The carriers, which were previously shown to be nontoxic to living organisms, were now tested if suitable for administration of candesartan, an antihypertensive drug. Spontaneously hypertensive rats (SHR) received injections of candesartan (0.1 mg/kg body weight per day; s.c.) in freshly prepared carriers for two weeks. The rats' arterial pressure was measured by telemetry. Urine and blood collection were performed in metabolic cages. In a separate group of SHR, the pharmacokinetics of the new formulation was evaluated after a single subcutaneous injection. The antihypertensive activity of candesartan administered in DOPE dispersions containing APrens was distinctly greater than that of candesartan dispersions composed of DOPE only or administered in the classic solvent (sodium carbonate). The pharmacokinetic parameters clearly demonstrated that candesartan in APren carriers reached the bloodstream more rapidly and in much greater concentration (almost throughout the whole observation) than the same drug administered in dispersions of DOPE only or in solvent. Serum creatinine (P-Cr) decreased significantly only in the group receiving candesartan in carriers with APrens (from 0.80 +/- 0.04 to 0.66 +/- 0.09 mg/dl; p < 0.05), whereas in the other groups PCr remained at the same level after treatment. Moreover, the new derivatives increased the loading capacity of the carriers, which is a valuable feature for any drug delivery system. Taken together, our findings led us to conclude that APrens are potentially valuable components of lipid-based drug carriers.
Cechy publikacji
discipline:Biologia medyczna
discipline:Medycyna
discipline:Medical biology
discipline:Medicine
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:864264
CrossrefMetadata from Crossref logo
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