International Journal of Applied Science and Engineering
Published by Chaoyang University of Technology

Mardhiah Maslizan1, Lai Yip Khen1, N. Idayu Zahid2, Shah Christirani Azhar3, Intan Diana Mat Azmi1,3*

1 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

2 Centre for Fundamental and Frontier Sciences in Nanostructure Self-Assembly, Department of Chemistry, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

3 Centre of Foundation Studies for Agricultural Science, Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

 

Download Citation: |
Download PDF


ABSTRACT

Lyotropic liquid crystalline nanoparticles (LLCNPs) have recently received much attention in the application of drug delivery systems, due to their ordered and versatile internal nanostructures that are considered as a key factor in improving loading efficiency of various poorly soluble therapeutic agents. To take advantage on their unique well-defined and flexible internal nanostructures, aripiprazole-loaded LLCNPs consisted of a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) were developed in this study. Despite exhibiting low aqueous solubility which lead to difficulties in formulation, aripiprazole, a class of psychotropic drug called atypical anti-psychotics has been used in the treatment of schizophrenia and bipolar disorder with few side effects. The utmost interest in this study is to explore the potential of LLCNPs in improving the percentage of encapsulation efficiency (EE%) of aripiprazole, their effect on the internal nanostructure of LLCNPs mesophases as well as the drug release performance from LLCNPs. The particle size of drug-loaded LLCNPs produced was in the range of 161–186 nm, with polydispersity index (PDI) between 0.11–0.16, and negative zeta potential of -21.5 to -23.8 mV. Small-angle X-ray scattering (SAXS) measurements indicated that the internal nanostructures of LLCNPs are of inverse hexagonal (H2) with a negligible difference in the lattice parameter before and after drug loading. Transmission electron microscopy (TEM) was used to observe the morphology and overall size distribution of drug-free and drug-loaded nanodispersions, which supported both SAXS and particles size findings. Differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy demonstrated that aripiprazole interacted physically with binary mixture of citrem/SPC within the nanodispersions. Moreover, the results showed that aripiprazole was successfully encapsulated into LLCNPs nanoparticles, where the EE% was all above 92%. These LLCNPs were not only have a high EE% value, but also exhibited a sustained release performance of aripiprazole with the release capacity of around 97% up to 96 h. From the current study, the potential use of LLCNPs as a promising nanocarrier for aripiprazole delivery is anticipated to improve the pharmacokinetics of this drug whilst enduring the internal nanostructural stability of the LLCNPs upon exposure to physiological environment.


Keywords: Liquid crystalline, Nanoparticles, Aripiprazole, Drug release.


Share this article with your colleagues

 


REFERENCES

  1. Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S.W., Zarghami, N., Hanifehpour, Y., Samiei, M., Kouhi., M., Nejati-Koshki, K. 2013. Liposome: classification, preparation, and applications. Nanoscale Research Letters, 8, 102.

  2. Ardiana, F., Lestari, M.L.A.D., Indrayanto, G. 2013. Aripiprazole: In profiles of drug substances, excipients and related methodology, 38, 2–501.

  3. Asha Spandana, A.K.M., Natarajan, J., Thirumaleshwar, S., Hemanth Kumar, S. 2020. A review of the preparation, characterization and application of nanostructured lipid carriers. International Journal of Research in Pharmaceutical Sciences, 11, 1130–1135.

  4. Ayala, A.P., Honorato, S.B., Filho, J.M., Grillo, D., Quintero, M., Gilles, F., Polla, G. 2010. Thermal stability of aripiprazole monohydrate investigated by raman spectroscopy. Vibrational Spectroscopy, 54, 169–173.

  5. Azmi, I.D.M., Wibroe, P.P., Wu, L.P., Kazem, A.I., Amenitsch, H., Moghimi, S.M., Yaghmur, A. 2016. A structurally diverse library of safe-by-design citrem-phospholipid lamellar and non-lamellar liquid crystalline nano-assemblies. Journal of Controlled Release, 239, 1–9.

  6. Babu, C., Kumara Babu, P., Sudhakar, K., Subha, M.C.S., Chowdoji Rao, K. 2014. Aripiprazole-loaded PLGA nanoparticles for controlled release studies: Effect of co-polymer ratio. International Journal of Drug Delivery, 6, 151–155.

  7. Badr-Eldin, S.M., Ahmed, T.A., Ismail, H.R. 2013. Aripiprazole-cyclodextrin binary systems for dissolution enhancement: Effect of preparation technique, cyclodextrin type and molar ratio. Iranian Journal of Basic Medical Sciences, 16, 1223–1231.

  8. Bastos, M. 2016. Using DSC to characterize thermotropic phase transitions in lipid bilayer membranes: The basics of liposome sample preparation and DSC studies. Malvern Instruments Limited, 1–21.

  9. Begam, M., Datta, V.M., Gowda, D.V., Aravindaram, A.S., Siddaramiah. 2014. Development and characterization of co-ground mixtures and solid dispersions of aripiprazole with hydrophilic carriers. International Journal of Pharmacy and Pharmaceutical Sciences, 6, 552–557.

  10. Bhosale, R., Osmani, R.A., Harkare, B.R., Ghodake, P.P. 2013. Cubosomes: The inimitable nanoparticulate drug carriers. Scholars Academic Journal of Pharmacy, 2, 481–486.

  11. Bonate, P.L. 2011. Pharmacokinetics. Wiley Interdisciplinary Reviews: Computational Statistics, 3, 332–342.

  12. Braun, D.E., Gelbrich, T., Kahlenberg, V., Tessadri, R., Wieser, J., Griesser, U.J. 2009. Conformational polymorphism in aripiprazole: preparation, stability and structure of five modifications. Journal of Pharmaceutical Sciences, 98, 2010–2026.

  13. Cagel, M., Tesan, F.C., Bernabeu, E., Salgueiro, M.J., Zubillaga, M.B., Moretton, M.A., Chiappetta, D.A. 2017. Polymeric mixed micelles as nanomedicines: Achievements and perspectives. European Journal of Pharmaceutics and Biopharmaceutics, 113, 211–228.

  14. Cai, L., Lin, C., Yang, N., Huang, Z., Miao, S., Chen, X., Pan, J., Rao, P., Liu, S. 2017. Preparation and characterization of nanoparticles made from co-incubation of SOD and glucose. Nanomaterials, 7, 1–11.

  15. Cerpnjak, K., Zvonar, A., Gasperlin, M., Vrecer, F. 2013. Lipid based system as a promising approach for enhancing the bioavailability of poor water-soluble drugs. Acta Pharmaceutica, 63, 427–445.

  16. Chandrashekhar V.K. 2012. Lipid crystallization: From self-assembly to hierarchical and biological ordering. Nanoscale, 4, 5779–5791.

  17. Chime, S.A. Onyishi, I.V. 2013. Lipid-based drug delivery systems (LDDS): Recent advances and applications of lipids in drug delivery. African Journal of Pharmacy and Pharmacology, 7, 3034–3059.

  18. Chong, J.Y.T., Mulet, X., Boyd, B.J., Drummond, C.J. 2015. Steric stabilizers for cubic phase lyotropic liquid crystal nanodispersions (cubosomes). In Advances in Planar Lipid Bilayers and Liposomes, 21, 131–187.

  19. Chountoulesi, M., Perinelli, D.R., Forys, A., Trzebicka, B., Pispas, S., Demetzos, C. 2020. Liquid crystalline nanoparticles for drug delivery: the role of gradient and block copolymers on the morphology, internal organization and release profile. European Journal of Pharmaceutics and Biopharmaceutics, 1–62.

  20. Chountoulesi, M., Pippa, N., Pispas, S., Chrysina, E.D., Forys, A., Trzebicka, B., Demetzos, C. 2018. Cubic lyotropic liquid crystals as drug delivery carriers: Physicochemical and morphological studies. International Journal of Pharmaceutics, 550, 57–70.

  21. Dutta, L., Mukherjee, B., Chakraborty, T., Das, M.K., Mondal, L., Bhattacharya, S., Gaonkar, R.H., Debnath, M. C. 2018. Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain. Drug Delivery, 25, 504–516.

  22. Elezaby, R.S., Gad, H.A., Metwally, A.A., Geneidi, A.S., Awad, G.A. 2017. Self-assembled amphiphilic core-shell nanocarriers in line with the modern strategies for brain delivery. Journal of Controlled Release, 261, 43–61.

  23. Gabr, M.M., Mortada, S.M., Sallam, M.A. 2017. Hexagonal liquid crystalline nanodispersions proven superiority for enhanced oral delivery of rosuvastatin: In vitro characterization and in vivo pharmacokinetic study. Journal of Pharmaceutical Sciences, 106, 3103–3112.

  24. Guo, C., Wang, J., Cao, F., Lee, R.J., Zai, G. 2010. Lyotropic liquid crystal systems in drug delivery. Drug Delivery Today, 15, 1032–1040.

  25. Huang, Y., Gui, S. 2018. Factors affecting the structure of lyotropic liquid crystals and the correlation between structure and drug diffusion. RSC Advances, 8, 6978–6987.

  26. Huang, Y., Gui, S. 2018. Factors affecting the structure of lyotropic liquid crystals and the correlation between structure and drug diffusion. RSC Advances, 8, 6978–6987.

  27. Kalepu, S., Nekkanti, V. 2015. Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharmaceutica Sinica B, 5, 442–453.

  28. Khani, S., Keyhanfar, F., Amani, A. 2016. Design and evaluation of oral nanoemulsion drug delivery system of mebudipine, Drug Delivery, 23, 2035–2043.

  29. Krishna Sailaja, A., Amareshwar, P., Chakravarty, P. 2011. Formulation of solid lipid nanoparticles and their applications. Current Pharma Research, 1, 197–203.

  30. Kumar, A., Singh, H., Mishra, A., Mishra, A.K. 2020. Aripiprazole: An FDA Approved bioactive compound to treat schizophrenia- A mini review. Current Drug Discovery Technologies, 17, 23–29.

  31. Kumar, V.V., Chandrasekar, D., Ramakrishna, S., Kishan, V., Rao, Y.M., Diwan, P.V. 2007. Development and evaluation of nitrendipine loaded solid lipid nanoparticles: Influence of wax and glyceride lipids on plasma pharmacokinetics. International Journal of Pharmaceutics, 335, 167–175.

  32. Kumbhar, S.A., Kokare, C.R., Shrivastava, B., Gorain, B., Choudhury, H. 2021. Antipsychotic potential and safety profile of TPGS-based mucoadhesive aripiprazole nanoemulsion: Development and optimization for nose-to-brain delivery. Journal of Pharmaceutical Sciences, 110, 1761–1778.

  33. Larsson, M., Hill, A., Duffy, J. 2012. Suspension stability: Why particle size, zeta potential and rheology are important. Annual Transactions of the Nordic Rheology Society, 20, 209–214.

  34. Lertxundi, U., Hernandez, R., Medrano, J., Domingo-Echaburu, S., Garcia, M., Aguirre, C. 2018. Aripiprazole and impulse control disorders: Higher risk with the intramuscular depot formulation? International Clinical Psychopharmacology, 33, 56–58.

  35. Liu, K., Feng, Z., Shan, L., Yang, T., Qin, M., Tang, J., Zhang, W. 2017. Preparation, characterization, and antioxidative activity of bletilla striata polysaccharide/ chitosan microspheres for oligomeric proanthocyanidins. Drying Technology, 35, 1629–1643.

  36. Longo, A., Carotenuto, G., Palomba, M., De Nicola, S. 2011. Dependence of optical and microstructure properties of thiol-capped silver nanoparticles embedded in polymeric matrix. Polymers, 3, 1794–1804.

  37. Luangtana-Anan, M., Limmatvapirat, S., Nunthanid, J., Chalongsuk, R., Yamamoto, K. 2010. Polyethylene glycol on stability of chitosan micro-particulate carrier for protein. AAPS Pharm SciTech, 11, 1376–1382.

  38. Mahbubul, I.M., Saidur, R., Amalina, M.A., Elcioglu, E.B., Okutucu-Ozyurt, T. 2015. Effective ultrasonication process for better colloidal dispersion of nanofluid. Ultrasonic Sonochemistry, 26, 361–369.

  39. Malheiros, B., Dias de Castro, R., Lotierzo, M.C.G., Casadei, B.R., Barbosa, L.R.S. 2021. Design and manufacturing of monodisperse and malleable phytantriol-based cubosomes for drug delivery applications. Journal of Drug Delivery Science and Technology, 61, 102149.

  40. Maslizan, M., Azmi, I.D.M., Jaafar, A.M., Haris, M.S. 2021. Nanotechnology for molecular imaging of atherosclerosis: Current design and approaches. Journal of Advanced Research in Fluid Mechanics and Thermal Sciences, 81, 124–138.

  41. Modi, S., Anderson, B.D. 2013. Determination of drug release kinetics from nanoparticles: Overcoming pitfalls of the dynamic dialysis method. Molecular Pharmaceutics, 10, 3076–3089.

  42. Nethravani, G., Kishore Babu, M., Kalyani, V., Dakshinamurthy, D.V., Murali Krishna, G.V. 2014. Formulation and evaluation of aripiprazole-loaded liposomes for brain drug delivery. Journal of Chemical and Pharmaceutical Sciences, 7, 14–20.

  43. Olson, E. n.d. Zeta potential and colloidal chemistry. Particle Technology Labs, www.particletechlabs.com.

  44. Piazzini, V., Landucci, E., Urru, M., Chiarugi, A., Pellegrini-Giampietro, D.E., Bilia, A.R., Bergonzi, M.C. 2020. Enhanced dissolution, permeation and oral bioavailability of aripiprazole mixed micelles: In vitro and in vivo evaluation. International Journal of Pharmaceutics, 583, 119361.

  45. Popova, A.V., Hincha, D.K. 2011. Thermotropic phase behavior and headgroup interactions of the nonbilayer lipids phosphatidylethanolamine and monogalactosyldiacylglycerol in the dry state. BMC Biophysics, 4, 1–11.

  46. Saari, N.A.N., Mislan, A.A., Hashim, R., Zahid, N.I. 2018. Self-assembly, thermotropic, and lyotropic phase behavior of guerbet branched-chain maltosides. Langmuir, 34, 8962–8974.

  47. Savjani, K.T., Gajjar, A.K., Savjani, J.K. 2012. Drug solubility: Importance and enhancement techniques. International Scholarly Research Network Pharmaceutics, 1–10.

  48. Shirley, M., Perry, C.M. 2014. Aripiprazole (ABILIFY MAINTENA®): A review of its use as maintenance treatment for adult patients with schizophrenia. Drugs, 74, 1097–1110.

  49. Silki, Sinha, V.R. 2018. Enhancement of in vivo efficacy and oral bioavailability of aripiprazole with solid lipid nanoparticles. AAPS Pharm SciTech, 19, 1264–1273.

  50. Socrates, G. 2004. Infrared and raman characteristic group frequencies. Journal of Raman Spectroscopy, 35, 905.

  51. Spicer, P.T. 2004. Cubosomes: Bicontinuous liquid crystalline nanoparticles. Dekker Encyclopedia of Nanoscience and Nanotechnology, 881–892.

  52. Stuart, B.H. 2004. Infrared spectroscopy: Fundamentals and applications.

  53. Tan, A., Hong, L., Du, J.D., Boyd, B.J. 2018. Self-assembled nanostructured lipid systems: Is there a link between structure and cytotoxicity? Advanced Science, 6, 1–21.

  54. Thadanki, M., Kumari, P.S., Prabha, K.S. 2011. Overview of cubosomes: A nanoparticle. International Journal of Research in Pharmacy and Chemistry, 1, 535–541.

  55. Uner, M. 2006. Preparation, characterization and physico-chemical properties of Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC): Their benefits as colloidal drug carrier system. Pharmazie, 61, 375–386.

  56. William, H.D., Trevaskis, N.L., Charman, S.A., Shanker, R.M., Charman, W.N., Pouton, C.W., Christopher J. H. Porter. 2013. Strategies to address low drug solubility in discovery and development. Pharmacology Revision, 65, 315–499.

  57. Xu, Y., Liu, X., Lian, R., Wu, W. 2012. Enhanced dissolution and oral bioavailability of aripiprazole nanosuspension prepared by nanoprecipitation/ homogenization based on acid-base neutralization. International Journal of Pharmaceutics, 438, 287–295.

  58. Yaghmur, A., Mu, H. 2021. Recent advances in drug delivery applications of cubosomes, hexosomes, and solid lipid nanoparticles. Acta Pharmaceutica Sinica B, 11, 871–885.

  59. Zhai, J., Tran, N., Sarkar, S., Fong, C., Mulet, X., Drummond, C. 2017. Self-assembled lyotropic liquid crystalline phase behavior of monoolein-capric acid-phospholipid nanoparticulate systems. Langmuir, 33, 2571–2580.


ARTICLE INFORMATION

Received: 2021-07-17
Revised: 2022-01-02
Accepted: 2022-03-24
Available Online: 2022-11-28


Cite this article:

Maslizan, M., Khen, L.Y., Zahid, N.I., Azhar, S.C., Azmi, I.D.M. Formulation, characterization, and optimization of aripiprazole-loaded lyotropic liquid crystalline nanoparticle for sustained release and better encapsulation efficiency against psychosis disorder. International Journal of Applied Science and Engineering, 19, 2021268. https://doi.org/10.6703/IJASE.202212_19(4).004

 

 

  Copyright The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are cited.

Other people also read ...

doaj logo

 

2.3
2022CiteScore
 
 
48th percentile
Powered by  Scopus
 
 

SCImago Journal & Country Rank

IJASE - Most Read Articles

IJASE - Most popular articles