Aliskiren is a non-peptide, orally active renin inhibitor with poor absorption and low bioavailability (~2.6%). In order to improve the current drug delivery system, a commercially available, biodegradable copolymer, poly(lactide-co-glycolide) (PLGA), was employed for a nanoparticle (NP) reformulation of aliskiren. An emulsion-diffusion-evaporation technique was implemented where aliskiren and PLGA were dissolved in dichloromethane, ethyl acetate, or ethyl acetate/acetone. To an aqueous phase containing 0.25% w/v didodecyldimethylammonium bromide (DMAB) as stabilizer, the previously prepared organic phase was added drop-wise. Following sonication, NP diffusion was expedited with the addition of water, and the organic phase was evaporated to form a suspension. Centrifugation was performed at 10,000 rpm, and the supernatant was analyzed for drug entrapment efficiency via ultraviolet-visible spectroscopy as well as particle morphology with the use of a transmission electron microscope (TEM). Having the highest entrapment efficiency (82.68 ± 1.18 %), ethyl acetate was used as the organic solvent in further testing, such as examining the effects of variation in DMAB stabilizer concentration (0.10, 0.25, 0.50, or 1.00% w/v) and centrifugation speed (10,000 or 12,000 rpm). The optimum formulation was ascertained through observing certain NP characteristics, such as entrapment efficiency particle size, zeta potential, and polydispersity index (PDI). A NICOMP Particle Sizer was used to measure particle size, zeta potential, and PDI. The smallest NP size (67.27 ± 0.87 nm) was accomplished with 0.50% w/v DMAB concentration using a centrifugation speed of 12,000 rpm, while the highest zeta potential (18.73 ± 0.03 mV) was detected with the 1.00% w/v DMAB concentration and a 10,000 rpm centrifugation speed. Further, the best entrapment efficiency and PDI (82.68 ± 1.18 % and 0.15 ± 0.03, respectively) were accomplished with 0.25% w/v DMAB and centrifugation at 10,000 rpm. The most favorable formulation yielding the highest zeta potential (18.73 ± 0.03 mV) was observed when DMAB stabilizer was 1.00% w/v and centrifuged at 10,000 rpm. Particle size and entrapment efficiency for this formulation were 75.67 ± 0.89 nm and 71.62 ± 0.11 %, respectively.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:honors-1319 |
| Date | 01 May 2015 |
| Creators | Coleman, Jessica M, Ms. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Undergraduate Honors Theses |
| Rights | Copyright by the authors., http://creativecommons.org/licenses/by-nc-nd/3.0/ |
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