Development of Sustained Release "Nanopolypill" of Ischemic Heart Disease Drugs - An Experimental Study

ISSN: 1875-6786 (Online)
ISSN: 1573-4137 (Print)

Volume 11, 6 Issues, 2015

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Development of Sustained Release "Nanopolypill" of Ischemic Heart Disease Drugs - An Experimental Study

Current Nanoscience, 10(6): 816-826.

Author(s): Anjuman Arora, Nusrat Shafiq, Sanjay Jain, G.K. Khuller, Sadhana Sharma, Avaneesh K. Pandey and Samir Malhotra.

Affiliation: Department of Pharmacology, PGIMER, Chandigarh, India.


Background: The present study was planned to formulate, characterize and evaluate the pharmacokinetics of a novel “nanopolypill” comprising four commonly prescribed cardiovascular drugs, atorvastatin, aspirin, atenolol and candesartan.

Methods: The candidate drugs were loaded in Poly (DL-lactide-co-gycolide) (PLGA) by emulsion- diffusion-evaporation method. The formulations were evaluated for their size, morphology, drug loading and in vitro release individually. Single dose pharmacokinetic profiles of the nanoformulations alone and in combination, as a nanopolypill, were evaluated in Wistar rats.

Results: The candidate drugs were encapsulated inside PLGA with entrapment efficiencies ranging from 27.8%, 33.5%, 47.5% and 62.9% for aspirin, candesartan, atenolol and atorvastatin respectively. The nanoparticles ranged in size from 50 to 169 nm. In vitro release profile of the nanoformulation showed 100% release by day 6 in the physiological pH 7.4 set up with PBS (phosphate buffer saline) and by day 4-5 in the intestinal pH 1.2 and 8.0 set up SGF (simulated gastric fluid) and SIF (simulated intestinal fluid) respectively. In pharmacokinetic analysis a sustained-release for 6 days and significant increase in the mean residence time (MRT), as compared to the respective free drugs was noted [MRT of atorvastatin, atenolol, aspirin and candesartan changed from 12.9 to 75.75 hours, 8.5 to 74.19 hours, 15.8 to 53.06 hours, and 12.6 to 94.92 hours respectively].

Conclusions: We have shown for the first time that encapsulating atorvastatin, aspirin, atenolol and candesartan into a single nanoformulation, to get the “nanopolypill” is a feasible strategy which has a potential of decreasing pill burden.


Cardiovascular drug delivery, fixed-dose combinations, IHD, nanopolypill, pharmacokinetics, sustained release.

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Article Details

Volume: 10
Issue Number: 6
First Page: 816
Last Page: 826
Page Count: 11
DOI: 10.2174/1573413710666140512221814

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