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The antihypertensive effect of orally administered nifedipine‐loaded nanoparticles in spontaneously hypertensive rats
Author(s) -
Kim Young Il,
Fluckiger Laurence,
Hoffman Maurice,
LartaudIdjouadiene Isabelle,
Atkinson Jeffrey,
Maincent Thilippe
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700910
Subject(s) - nifedipine , bioavailability , pharmacology , polyethylene glycol , oral administration , blood pressure , dosage form , chemistry , peg ratio , medicine , biochemistry , finance , economics , calcium
1 The therapeutic use of nifedipine is limited by the rapidity of the onset of its action and its short biological half‐life. In order to produce a form devoid of these disadvantages we made nanoparticles of nifedipine from three different polymers, poly‐ɛ‐caprolactone (PCL), polylactic and glycolic acid (1:1) copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene glycol 400 (PEG) solution was used as a control. 2 The average diameters of the nanoparticles ranged from 0.12 to 0.21 μm; the encapsulation ratio was 82% to 88%. 3 In spontaneously hypertensive rats (SHR), the initial rapid fall in systolic arterial blood pressure following oral administration of nifedipine in PEG solution (from 193 ± 3 to 102 ± 2 mmHg) was not seen following administration of the same dose in Eudragit nanoparticles (from 189 ± 2 to 156 ± 2 mmHg); with PCL and PLAGA nanoparticles the initial fall in blood pressure was significantly reduced (nadirs PCL 124 ± 2 and PLAGA 113 ± 2 mmHg). Ten hours following administration, blood pressure in rats administered the nifedipine/PEG preparation had returned to normal (183 ± 3 mmHg) whereas that of animals given nifedipine in nanoparticles (PCL 170 ±3, PLAGA 168 ± 2, Eudragit 160 ±3 mmHg) was still significantly reduced. 4 All of the nanoparticle dosage forms decreased C max and increased T max and the mean residence time (MRT) values. Relative bioavailability was significantly increased with Eudragit nanoparticles compared to the nifedipine/PEG solution. 5 There was an inverse linear correlation between the fall in blood pressure and plasma nifedipine concentration with all preparations. 6 The nanoparticle nifedipine preparations represent sustained release forms with increased bioavailability, a less pronounced initial antihypertensive effect and a long‐lasting action.