Analysis of Process and Formulation Variables on Chitosan based Losartan Potassium Nanoparticles: Preparation, Validation and in vitro Release Kinetics

Author(s): Manisha Singh*, Ramneek Kaur, Rashi Rajput, Shriya Agarwal, Sachin Kumar, Malvika Sharma, Aishwarya Sharma

Journal Name: Recent Innovations in Chemical Engineering
Formerly Recent Patents on Chemical Engineering

Volume 13 , Issue 1 , 2020

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Graphical Abstract:


Background: Although many potential therapeutic compounds have been discovered and have exhibited a promising recovery, their effective delivery in the human system has always remained questionable with many pharmacological constraints in delivering them. Amidst all this, the concept of nanomedicine has always assured the potential to overcome the drug delivery complications in the present treatment methods. Losartan Potassium (LP) is indicated in the management of hypertension. Owing to its moderate bioavailability (32%) and a number of side effects due to the oral dosage forms of LP thus, nanoparticles based delivery would be beneficial.

Objective: The present study is focused to develop a nanoparticle system of Losartan Potassium, an Angiotensin II receptor antagonist and a well-known promising antihypertensive drug, to conquer its limitation of bioavailability and potential adverse effects.

Methods: LP Loaded Polymeric Nanoparticles (LP-NPs) were developed by ionic gelation method using Chitosan (CH) and Tripolyphosphate (TPP) for cross linkage in various optimising ratios. After the successful optimisation and synthesis of LP-NPs, the optimised formulation was further characterized by Particle Size Analysis (PSA), Polydispersity Index (PDI), Zeta Potential (ZP), TEM analysis with the in vitro cytotoxicity and permeability evaluation.

Results: The results showed the average size of 123.5 ± 1.23nm with polydispersibility score of 0.257 ± 0.079 and charge of -2.74 mV respectively. Further, Transmission Electron Microscopy (TEM) images showed the size range in almost conformity with DLS findings, representing the spherical and smooth morphology. In vitro drug release kinetics estimation showed sustained release routine of the drug and the cell viability studies done on Jurkat cell line displayed lesser cytotoxicity of LP-NPs (99.3 ± 2.28% and 98.17 ± 1.86%) in comparison with the LP only (85.3 ± 2.1% and 71.7 ± 1.07%) at different time periods (12 hours and 24 hours).

Conclusion: The aforementioned results confirm the effective fabrication of LP-NPs and indicate that it may further, used on higher model systems to investigate the above parameters and their enhanced effectiveness in hypertension.

Keywords: Antihypertensive, chitosan, particle size analysis, drug release kinetics, Transmission Electron Microscopy (TEM), polymeric nanoparticle.

Booth FW, Lees SJ. Fundamental questions about genes, inactivity, and chronic diseases. Physiol Genomics 2007; 28(2): 146-57.
Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med 2003; 139(9): 761-76.
Burt VL, Whelton P, Roccella EJ, et al. Prevalence of hypertension in the US adult population. Hypertension 1995; 25(3): 305-13.
Goa KL, Wagstaff AJ. Losartan potassium. Drugs 1996; 51(5): 820-45.
Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007; 292(1): C82-97.
Atlas SA. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Spec Pharm 2007; 13(8)(Suppl. B): 9-20.
Abraham HMA, White CM, White WB. The Comparative Efficacy and Safety of the Angiotensin Receptor Blockers in the Management of Hypertension and Other Cardiovascular Diseases. Drug Saf 2015; 38(1): 33-54.
Marin E, Briceño MI, Caballero-George C. Critical evaluation of biodegradable polymers used in nanodrugs. Int J Nanomedicine 2013; 8: 3071-90.
Khadka P, Ro J, Kim H, et al. Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm 2014; 9(6): 304-16.
Singh R, Lillard Jr JW. Nanoparticle-based targeted drug delivery. Exp Mol Pathol 2009; 86(3): 215-23.
Patil P, Chavanke D, Wagh M. A review on ionotropic gelation method: novel approach for controlled gastroretentive gelispheres. Int J Pharm Pharm Sci 2012; 4(4): 27-32.
Usmiati S, Richana N, Mangunwidjaja D, et al. The using of ionic gelation method based on polysaccharides for encapsulating the macromolecules- A review. Int Proc Chem Biol Environ Eng 2014; 67(1): 79-84.
Kaur R, Rajput R, Nag P, et al. Synthesis, characterization and evaluation of antioxidant properties of catechin hydrate nanoparticles. J Drug Deliv Sci Technol 2017; 39(1): 398-407.
Akbari B, Tavandashti MP, Zandrahimi M. Particle Size Characterization of Nanoparticles- A Practicalapproach. Iranian J Mater Scie Eng 2011; 8(2): 48-56.
Weiner BB, Tscharnuter WW, Fairhurst D. Zeta potential: A new approach. Canadian Mineral Analysts Meeting. 1993
Kharia A, Singhai A, Verma R. Formulation and evaluation of polymeric nanoparticles of an antiviral drug for gastroretention. Int J Pharm Sci Nanotechnol 2012; 4(4): 1557-62.
Pennycook SJ, Lupini AR, Borisevich A, et al. Transmission electron microscopy: Overview and challenges. AIP Conference Proceedings 2003; 683(1): 627-33.
Singh M, Singh SP, Rachana R. Development, characterization and cytotoxicity evaluation of Gingko biloba extract (EGB761) loaded microemulsion for intra-nasal application. J Appl Pharm Sci 2017; 7(1): 24-34.
Stockert JC, Blázquez-Castro A, Cañete M, et al. MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets. Acta Histochemica 2012; 114(8): 785-96.
Saïed N, Aïder M. Zeta potential and turbidimetry analyzes for the evaluation of chitosan/phytic acid complex formation. J Food Res 2014; 3(2): 71-81.
Madgulkar A, Bhalekar M, Swami M. In Vitro and in vivo studies on chitosan beads of losartan duolite ap143 complex, optimized by using statistical experimental design. AAPS Pharm Sci Tech 2009; 10(3): 743-51.
Fan W, Yan W, Xu Z, et al. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surf B Biointerfaces 2012; 90(1): 21-7.
Kaur R, Rajput R, Nag P, et al. Synthesis, characterization and evaluation of antioxidant properties of catechin hydrate nanoparticles. J Drug Deliv Sci Technol 2017; 39(1): 398-407.
Lee DW, Yun K-S, Ban H-S, et al. Preparation and characterization of chitosan/polyguluronate nanoparticles for siRNA delivery. J Controlled Release 2009; 139(2): 146-52.
Ostolska I, Wiśniewska M. Application of the zeta potential measurements to explanation of colloidal Cr2O3 stability mechanism in the presence of the ionic polyamino acids. Colloid Polym Sci 2014; 292(10): 2453-64.
Freitas C, Müller RH. Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN™) dispersions. Int J Pharm 1998; 168(2): 221-9.
Xu Y, Du Y. Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. Int J Pharm 2003; 250(1): 215-26.

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Article Details

Year: 2020
Page: [41 - 54]
Pages: 14
DOI: 10.2174/2405520412666190502161137
Price: $65

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