Enhancement of In Vivo Efficacy and Oral Bioavailability of Aripiprazole with Solid Lipid Nanoparticles
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Aripiprazole (ARP), a second-generation or atypical antipsychotic, is poorly soluble and undergoes extensive hepatic metabolism and P-glycoprotein efflux which lead to reduced in vivo efficacy and increased dose-related side effects. To enhance in vivo efficacy and oral bioavailability of aripiprazole, aripiprazole-loaded solid lipid nanoparticles (SLNs) were developed using tristearin as solid lipid. Tween 80 and sodium taurocholate were used as surfactants to prepare SLNs using microemulsification method. SLNs were characterized for particle size, zeta potential, entrapment efficiency, and crystallinity of lipid and drug. In vitro release studies were performed in water containing 0.5% sodium dodecyl sulfate. Pharmacodynamic evaluation was carried out in laca mice using dizocilpine-induced schizophrenic model where behavioral evaluation revealed better in vivo efficacy of SLNs. Pharmacokinetics of aripiprazole-loaded SLNs after oral administration to conscious male Wistar rats was studied. Bioavailability of aripiprazole was increased 1.6-fold after formulation of aripiprazole into SLNs as compared to plain drug suspension. The results indicated that solid lipid nanoparticles can improve the bioavailability of lipophilic drugs like aripiprazole by enhancement of absorption and minimizing first-pass metabolism.
KEY WORDSaripiprazole solid lipid nanoparticles antischizophrenic solid lipid nanoparticles bioavailability enhancement dizocilpine-induced schizophrenia
The authors are thankful to Unichem Laboratories, India for providing aripiprazole samples ex-gratis
Compliance with Ethical Standards
The study was previously approved by Institutional Animal Ethics Committee (IAEC, UIPS, Panjab University, Chandigarh). The experiments were conducted as per CPCSEA guidelines (Committee for Prevention, Control, and Supervision of Animal Experiments).
- 1.Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment options. P&T®. 2014;39 (9):638–345.Google Scholar
- 2.Wig NN, Varma VK, Mattoo SK, Bedi HS. An incidence study of schizophrenia in India. Indian J Psychiatry. 1993;35(1):11–7.Google Scholar
- 6.Ying X, Liu X, Lian R, Zheng S, Yin Z, Lu Y, et al. Enhanced dissolution and oral bioavailability of aripiprazole nanosuspensions prepared by nanoprecipitation/homogenization based on acid-base neutralization. Int J Pharm. 2012;438(1–2):287–95. https://doi.org/10.1016/j.ijpharm.2012.09.020.Google Scholar
- 8.Raza K, Singh B, Singal P, Wadhwa S, Katare OP. Systematically optimized biocompatible isotretinoin-loaded solid lipid nanoparticles (SLNs) for topical treatment of acne. Colloids Surf B: Biointerfaces. 2013;105:67–74. https://doi.org/10.1016/j.colsurfb.2012.12.043.
- 16.Sood S, Jawahar N, Jain K, Gowthamarajan K, Meyyanathan SN. Olanzapine loaded cationic solid lipid nanoparticles for improved oral bioavailability. Curr Nanosci. 2013;9:26–34.Google Scholar
- 18.Rehman M, Madni A, Ihsan A, Khan WS, Khan MI, Mahmood MA, et al. Solid and liquid lipid-based binary solid lipid nanoparticles of diacerein: in vitro evaluation of sustained release, simultaneous loading of gold nanoparticles, and potential thermoresponsive behavior. Int J Nanomedicine. 2015;10:2805–14. https://doi.org/10.2147/IJN.S67147.CrossRefGoogle Scholar
- 23.Kumar VV, Chandrasekar D, Ramakrishna S, Kishan V, Rao YM, Diwan PV. Development and evaluation of nitrendipine loaded solid lipid nanoparticles: influence of wax and glyceride lipids on plasma pharmacokinetics. Int J Pharm. 2007;335(1-2):167–75. https://doi.org/10.1016/j.ijpharm.2006.11.004.CrossRefGoogle Scholar
- 29.Pedersen CS, Sørensen DB, Parachikova A, Plath N. PCP-induced deficits in murine nest building activity: employment of an ethological rodent behavior to mimic negative-like symptoms of schizophrenia. Behav Brain Res 2014; 15: 273:63–72. doi: https://doi.org/10.1016/j.bbr.2014.07.023.
- 30.Lee SH, Lee MG. Pharmacokinetics and pharmacodynamics of azosemide after intravenous and oral administration to rats: absorption from various GI segments. J Pharmacokinet Biopharm. 1996;24(6):551-568.Google Scholar
- 32.Yang S, Zhu J, Lu Y, Liang B, Liang C. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm Res. 1999;16(5)Google Scholar
- 33.Hallan SS, Nidhi, Kaur V, Jain V, Mishra N. Development and characterization of polymer lipid hybrid nanoparticles for oral delivery of LMWH. Artif Cells Nanomed Biotechnol. 2017:1–12.Google Scholar