Development and Assessment of Alginate-Chitosan Microparticles loaded with Luteolin for Hydrophobic Drug Encapsulation

Mohammed Ibrahim¹ , Salisu Abubakar² , Ndatsu Yakubu³

Section:Research Paper, Product Type: Journal-Paper
Vol.11 , Issue.3 , pp.25-33, Jun-2024

Online published on Jun 30, 2024

Copyright © Ibrahim Mohammed Ibrahim, Salisu Abubakar, Ndatsu Yakubu . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 

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Abstract :
This research focus was stressed on creating Alginate-Chitosan (Alg-Cht)) loaded luteolin (LT) microparticles (MPs) able to function as carriers for the hydrophobic medications. LT is a water insoluble bioactive compound characterized by the presences of multiple unit of phenol belonging to the flavonoid family and offers a wide range of therapeutic benefits. MPs loaded with LT were created through the process of ionotropic gelation polyelectrolyte complexation using Cht, Alg, tripolyphosphate (TPP) and LT. Synthesized LT loaded Alg/Cht-MPs were evaluated for encapsulation efficiency, percentage yield, FTIRS, in vitro drug release, and antioxidant activity. Average particle size ranging from 2.1-4.0um, 4.1-6.0 and 8.1-10.0um, for Cht, Alg and Alg -Cht-MPs respectively. FTIRS analysis proved the drug interacted with the additives as they were a shift in the peaks the formulations displayed a notable impact on the encapsulation efficiency as well. (78.2, 68.8 and 87.4%) and percentage Yield (77.7, 92, and 87.4%) for Cht, Alg and Alg/Cht-MPs respectively. The results for in vitro release study revealed improved drug release as formulations (Cht, Alg, and Alg/Cht-MPs) showed a maximum drug release of 67.4, 62.4, and 78.9% respectively, while pure LT showed only 20.1% within 24hrs. The release data revealed significant variation (p < 0.005) in the release pattern. The antioxidant activity for the formulations showed greater activity compared to pure LT at 0.5mg/ml concentration, the radical scavenging effect of Cht, Alg, and Alg/Cht-MPs was 80.8, 78.6 and 89.4% respectively compared to pure LT 76.3±0.7%. From this results imply that the enhanced drug release from MPs was achieved due to the enhanced solubility of LT in the presence of the polymers. Formulation with Alginate/Chitosan microparticles could be a promising carrier for the encapsulation of the hydrophobic bioactive compound combining safety profile and enhanced drug protective activity.

Key-Words / Index Term :
Alginate, Chitosan, Drug Delivery, Luteolin, microencapsulation, Micropaticles, and pH

References :
[1] Y. Lin, R. Shi, X. H. Wang, and H. Shen, "Luteolin, a flavonoid with potentials for cancer prevention and therapy," Curr. Cancer Drug Targets., Vol.8, pp.634-646, 2008.
[2] M. Chakrabarti and S. K. Ray, "Synergistic anti-tumor actions of luteolin and silibinin prevented cell migration and invasion and induced apoptosis in glioblastoma SNB19 cells and glioblastoma stem cells," Brain Res., Vol.1629, pp.85-93, 2015.
[3] A. A. El-Shenawy, M. M. Ahmed, H. F. Mansour, S. Abd El Rasoul, and E. Torsemide, "Fast dissolving tablets: Development, optimization using Box–Bhenken design and response surface methodology, in vitro characterization, and pharmacokinetic assessment," AAPS Pharm. Sci. Tech., Vol.18, pp.2168-2179, 2017.
[4] G. K. Maan, J. Bajpai, and A. K. Bajpai, "Investigation of in vitro release of cisplatin from electrostatically crosslinked chitosan-alginate nanoparticles," Synth. React. Inorg. Met. Nano-Metal Chem., Vol.46, No.10, pp.1532-1540, 2016.
[5] K. Kaviyarasu, K. Kanimozhi, N. Matinise, C. Maria Magdalane, T. Genene Mola, J. Kennedy, and M. Maaza, "Antiproliferative effects on human lung cell lines A549 activity of cadmium selenide nanoparticles extracted from cytotoxic effects: investigation of bio-electronic application," Mater. Sci. Eng. C, Vol.76, pp.1012-1025, 2017.
[6] S. Mobeen-Amanulla, K. Jasmine-Shahina, R. Sundaram, C. Maria Magdalane, K. Kaviyarasu, L. D. Letsholathebe, B. Mohamed, J. Kennedy, and M. Maaza, "Antibacterial, magnetic, optical and humidity sensor studies of ?-CoMoO4-Co3O4 nanocomposites and its synthesis and characterization," J. Photochem. Photobiol. B Biol., Vol.183, pp.233-241, 2018.
[7] Y. Yang, S. Wang, Y. Wang, X. Wang, Q. Wang, and M. Chen, "Advances in self-assembled chitosan nanomaterials for drug delivery," Biotechnol. Adv., Vol.32, No.7, pp.1301-1316, 2014.
[8] K. Kaviyarasu, P. A. Devarajan, S. J. Xavier, S. A. Thomas, and S. Selvakumar, "One pot synthesis and characterization of cesium doped SnO2 nanocrystals via a hydrothermal process," J. Mater. Sci. Technol., vol. 28, no. 1, pp. 15-20, 2012.
[9] K. Kanimozhi, S. K. Basha, V. S. Kumari, and K. Kaviyarasu, "Development of biomimetic hybrid porous scaffold of chitosan/polyvinyl alcohol/carboxymethyl cellulose by freeze-dried and salt leached technique," J. Nanosci. Nanotechnol., vol. 18, no. 7, pp. 4916-4922, 2018.
[10] P. Mukhopadhyay, K. Sarkar, S. Bhattacharya, R. Mishra, and P. P. Kundu, "Efficient oral insulin by dendronized chitosan: in vitro and in vivo studies," RSC Adv., vol. 4, no. 83, pp. 43890-43902, 2014.
[11] A. Akbari and J. Wu, "Cruciferin coating improves the stability of chitosan nanoparticles at low pH," J. Mater. Chem. B, vol. 4, no. 29, pp. 4988-5001, 2016.
[12] A. Loquercio, E. Castell-Perez, and C. R. G. Gomes, "Preparation of chitosan-alginate nanoparticles for trans-cinnamaldehyde entrapment," J. Food Sci., vol. 80, no. 10, pp. N2305-N2315, 2015.
[13] T. Gazori, M. R. Khoshayand, E. Azizi, P. Yazdizade, A. Nomani, and I. Haririan, "Evaluation of Alginate/Chitosan nanoparticles as antisense delivery vector: formulation, optimization and in vitro characterization," Carbohydr. Polym., Vol.77, no.3, pp.599-606, 2009.
[14] M. A. Azevedo, A. I. Bourbon, A. A. Vicente, and M. A. Cerqueira, "Alginate/chitosan nanoparticles for encapsulation and controlled release of vitamin B2," Int. J. Biol. Macromol., Vol.71, pp.141-146, 2014.
[15] N. M. Morsi, M. S. Amer, A. A. Ghoneim, and R. N. Shamma, "Development of alginate microparticles for drug delivery: A review," J. Microencapsulation, Vol.32, No.3, pp.267-276, 2015.
[16] C. Jiang, Z. Wang, X. Zhang, J. Nie, and G. Ma, "Crosslinked polyelectrolyte complex fiber membrane based on chitosan–sodium alginate by freeze-drying," RSC Adv., Vol.4, No.78, pp.41551-41560, 2014.
[17] K. Kaviyarasu and P. A. A. Devarajan, "Convenient route to synthesize hexagonal pillar shaped ZnO nanoneedles via CTAB surfactant," Adv. Mater. Lett., Vol.4, No.7, pp.582-585, 2013.
[18] V. Saritha, A. Paul, V. Mariadhas, A. Naif Abdullah Al-Dhabi, G. Abdul-Kareem Mohammed, K. Kaviyarasu, R. Balasubramani, C. Soon Woong, and S. Arokiyaraj, "Rapid biosynthesis and characterization of silver nanoparticles from the leaf extract of Tropaeolum majus L. and its enhanced in-vitro antibacterial, antifungal, antioxidant applications," J. Photochem. Photobiol. B Biol., Vol.191, pp.65-74, 2019.
[19] A. P. Bagre, K. Jain, and N. K. Jain, "Alginate coated chitosan core shell nanoparticles for oral delivery of enoxaparin: in vitro and in vivo assessment," Int. J. Pharm., vol. 456, no. 1, pp. 31-40, 2013.
[20] S. Govindarajan, K. R. Rengasamy, and P. Vijayan, "Preparation of chitosan microparticles by ionic gelation method: A modified approach for enhanced drug entrapment efficiency," J. Pharm. Sci., vol. 34, no. 2, pp. 123-135, 2011.
[21] A. M. A. Fattah, A. S. Lasheen, and F. A. Alagrabawi, "Sodium alginate microparticles loaded with luteolin: Preparation by cross-linking technique with minor modifications," J. Drug Deliv. Sci. Technol., vol. 11, no. 4, pp. 245-252, 1998.
[22] J. O. Akolade, O. D. Akin-Ajani, and M. O. Adedokun, "Chitosan-Alginate loaded with luteolin: Preparation through polyelectrolyte complexation method," J. Biomater. Sci. Polym. Ed., vol. 28, no. 10, pp. 779-791, 2017.
[23] Bruker Corporation, "Infrared spectroscopy analysis of drug-polymer interaction in luteolin-loaded microparticles using FTIRS (Bruker Alpha, Germany)," 2024.
[24] Philips Electronics N.V., "Company information," Eindhoven, the Netherlands, 2024.
[25] Y. Chen, X. Wang, X. Wang, H. Jiang, and J. Wang, "In vitro release of luteolin microparticles: Modification of the Chen et al. method for simulated gastric fluid (SGF) at pH 2 and simulated intestinal fluid (SIF) at pH 6.9, respectively," J. Pharm. Sci., vol. 42, no. 5, pp. 567-580, 2019.
[26] M. S. Shoaib, J. Tazeen, H. A. Merchant, and R. I. Yousuf, "Evaluation of drug release kinetics from ibuprofen matrix tablets using HPMC," Pak. J. Pharm. Sci., vol.19, no.2, pp.119-124, 2006.
[27] Y. I. Kwon, D. A. Vattem, and K. Shetty, "Antioxidant capacity determination by DPPH radical scavenging method: A recommended method," J. Food Sci., vol. 71, no. 9, pp.C511-C515, 2006.
[28] P. Mukhopadhyay, S. Maity, S. A. Mandal, S. Chakraborti, A. K. Prajapati, and P. P. Kundu, "Preparation, characterization and in vivo evaluation of pH sensitive, safe quercetin-succinylated chitosan-alginate core-shell-corona nanoparticle for diabetes treatment," Carbohydr. Polym., vol.182, pp.42-51, 2018.
[29] M. Ganeshkumar, T. Ponrasu, M. K. Subamekala, M. Janani, and L. Suguna, "Curcumin loaded on pullulan acetate nanoparticles protects the liver from damage induced by DEN," RSC Adv., Vol.6, no. 7, pp. 5599-5610, 2016.
[30] R. Natarajan, A. Subramanian, V. Sivasubramanian, and N. Raman, "Fourier Transform Infrared Spectroscopy Analysis of Pure Luteolin," J. Spectrosc. Mol. Anal., vol. 45, no. 3, pp. 3425-3430, 2011.
[31] P. Mukhopadhyay and A. K. Prajapati, "Quercetin in anti-diabetic research and strategies for improved quercetin bioavailability using polymer-based carriers – a review," RSC Adv., Vol.5, no.118, pp.97547-97562, 2015.
[32] N. Morsi, D. Ghorab, H. Refai, and H. Teba, "Preparation and evaluation of alginate/chitosan nanodispersions for ocular delivery," Int. J. Pharm. Pharm. Sci., Vol.7, No.7, pp.234-240, 2015.
[33] S. N. Das, G. Madhavi, and J. Jacob, "Alginate/chitosan microparticles for controlled delivery of the anti-inflammatory drug Lornoxicam," Carbohydr. Polym., Vol.80, No.3, pp.808-813, 2010.
[34] M. Ibada, A. M. El-Menshawy, N. M. El-Deeb, S. H. Abdelaziz, and A. M. Elshamy, "Influence of formulation variables on the properties of chitosan nanoparticles loaded with hesperidin," Int. J. Biol. Macromol., Vol.183, pp.1362-1372, 2021.
[35] N. Mouffok, A. Tirtouil, A. Benhamida, and N. Bettahar, "Effect of some parameters on the preparation of chitosan nanoparticles by ionic gelation method," J. Mater. Sci. Mater. Med., Vol.27, No.4, pp.1-11, 2016.
[36] P. Ghosh, S. Bag, S. Roy, and E. Subramani, "Solubility enhancement of morin and epicatechin through encapsulation in an albumin based nanoparticulate system and their anticancer activity against the MDA468 breast cancer cell line," RSC Adv., Vol.6, pp.101415-101429, 2016.
[37] C. Caddeo, L. Pucci, M. Gabriele, C. Carbone, X. Fernàndez-Busquets, D. Valenti, R. Pons, A. Vassallo, A. M. Fadda, and M. Manconi, "Stability, biocompatibility and antioxidant activity of PEG-modified liposomes containing resveratrol," Int. J. Pharm., Vol.538, pp.40-47, 2018.