10.57647/pibm.2024.132402

Development and Characterization of ZnO-Loaded Solid Lipid Nanoparticles for Oral Delivery: Physicochemical, Cytocompatibility, and Antibacterial Evaluation

  1. Department of Chemistry, SR.C., Islamic Azad University, Tehran, Iran
  2. Department of Chemistry, TeMS.C., Islamic Azad University, Tehran, Iran

Published in Issue 2024-03-30

How to Cite

Inanloo, Z., Yousefi, M., & Baniyaghoob, S. (2024). Development and Characterization of ZnO-Loaded Solid Lipid Nanoparticles for Oral Delivery: Physicochemical, Cytocompatibility, and Antibacterial Evaluation. Progress in Biomaterials, 13(1). https://doi.org/10.57647/pibm.2024.132402

Abstract

Chitosan-coated solid lipid nanoparticles loaded with zinc oxide (ZnO-CS-SLNs) were developed to enhance oral zinc delivery and improve formulation performance. The nanoparticles were synthesized via a microemulsion technique and exhibited spherical morphology, an average diameter of 91.2 ± 2.8 nm, a positive zeta potential (+25 mV), and high encapsulation efficiency (90 ± 3%), quantified using ICP-OES. FTIR, DSC, and XRD analyses confirmed structural integrity and uniform ZnO distribution within the lipid matrix. FE-SEM and TEM imaging revealed homogeneous particles with no signs of aggregation. In vitro release studies conducted in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids demonstrated sustained release profiles reaching up to 93% over 24 hours, consistent with Higuchi kinetics. Cytotoxicity assays on AGS cells indicated excellent biocompatibility, with cell viability exceeding 100% across all tested concentrations. Antibacterial activity of ZnO-002 was validated against Gram-positive and Gram-negative strains using disk diffusion, MIC, and MBC assays. Accelerated stability testing over six months (40 ± 2 °C, 75 ± 5% RH) confirmed the physical and colloidal stability of the formulations. Collectively, these results support ZnO-CS-SLNs as a robust oral delivery system with multifunctional attributes and consistent in vitro performance.

Keywords

  • Zinc oxide,
  • Solid lipid nanoparticles,
  • Chitosan,
  • Oral delivery,
  • Bioavailability,
  • Antimicrobial activity,
  • Cytocompatibility,
  • Sustained release

References

  1. Prasad AS. Zinc in human health: effect of zinc on immune cells. Curr Opin Clin Nutr Metab Care. 2008;11(6):646-52. doi: 10.1097/MCO.0b013e3283138ab4
  2. King JC. Zinc: an essential but elusive nutrient. Am J Clin Nutr. 2011;94(2 Suppl):679S-84S. doi: 10.3945/ajcn.110.005744
  3. Black RE. Trace element undernutrition: biology to interventions. J Nutr. 2003;133(5 Suppl 1):1485S-9S. doi: 10.1093/jn/133.5.1485S
  4. Brown KH, Wuehler SE, Peerson JM. The importance of zinc in human nutrition and estimation of the global prevalence of zinc deficiency. Food Nutr Bull. 2001;22(2):113-25. doi: 10.1177/156482650102200201
  5. Trivedi SS, Chudasama RK, Patel N. Effect of zinc supplementation in children with acute diarrhea: randomized double blind controlled trial. Gastroenterol Res. 2009;2(3):137-42. doi: 10.4021/gr2009.06.1297
  6. Mishra PK, Mishra H, Ekielski A, Talegaonkar S, Vaidya B. Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications. Drug Discov Today. 2017;22(12):1825-34. doi: 10.1016/j.drudis.2017.08.006
  7. Allen L, de Benoist B, Dary O, Hurrell R, editors. Guidelines on food fortification with micronutrients. Geneva: World Health Organization; 2006
  8. Salgueiro MJ, Zubillaga MB, Lysionek AE, Caro RA, Weill R, Boccio JR. The role of zinc in the growth and development of children. Nutr Res. 2002;22(7):1005-15. doi: 10.1016/S0271-5317(02)00418-8
  9. Mehnert W, Mäder K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2-3):165-96. doi: 10.1016/S0169-409X(01)00105-3
  10. Ekambaram P, Sathali AAH, Priyanka K. Solid lipid nanoparticles: a review. Sci Revs Chem Commun. 2012;2(1):80-102
  11. Mahajan PS, Mahajan KB, Darekar AB. A review on solid lipid nanoparticle (SLN): an advanced treatment modality. Int J Pharm Sci Res. 2015;6(9):3698-712. doi: 10.13040/IJPSR.0975-8232.6(9).3698-3712
  12. Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54 Suppl 1:S131-55. doi: 10.1016/S0169-409X(02)00118-7
  13. Bernkop-Schnürch A, Dünnhaupt S. Chitosan-based drug delivery systems. Eur J Pharm Biopharm. 2012;81(3):463-9. doi: 10.1016/j.ejpb.2012.04.007
  14. Mohammed MA, Syeda JTM, Wasan KM, Wasan EK. An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics. 2017;9(4):53. doi: 10.3390/pharmaceutics9040053
  15. Hosseini SM, Abbasalipourkabir R, Jalili C, Zarei L. Preparation of a nanoliposomal carrier for the oral delivery of zinc and the evaluation of its stability, cytotoxicity, and bioaccessibility. J Food Sci. 2020;85(12):4263-71. doi: 10.1111/1750-3841.15532
  16. Raghupathi KR, Koodali RT, Manna AC. Size-dependent bacterial growth inhibition and mechanism of antibacterial activity of zinc oxide nanoparticles. Langmuir. 2011;27(7):4020-8. doi: 10.1021/la104825u
  17. Pignatello R, Leonardi A, Fuochi V, Petronio GP, Greco AS, Furneri PM. A method for efficient loading of ciprofloxacin hydrochloride in cationic solid lipid nanoparticles: formulation and microbiological evaluation. Nanomaterials (Basel). 2018;8(5):304. doi: 10.3390/nano8050304
  18. Scioli-Montoto S, Allemann E, Mattos AC, Espina M, Souza J, García ML, et al. Solid lipid nanoparticles for drug delivery: A review of the state of the art. Front Mol Biosci. 2020;7:587997. doi:10.3389/fmolb.2020.587997
  19. PubChem. 1-Butanol. National Center for Biotechnology Information. PubChem Compound Summary for CID 263. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/1-Butano
  20. National Toxicology Program. Toxicological profile for 1-Butanol. Toxicol Ind Health. 2008;24(9):597-606. PMID:18830864. doi:10.1177/0748233708098116
  21. U.S. Food and Drug Administration (FDA). Inactive Ingredient Database (IID). Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/inactive-ingredients-databas
  22. Date AA, Hanes J, Ensign LM. Nanoparticles for oral delivery: design, evaluation and state-of-the-art. J Control Release. 2016;240:504-26. doi:10.1016/j.jconrel.2016.06.016
  23. Winter E, Pizzol CD, Locatelli C, Creczynski-Pasa TB. Development and evaluation of lipid nanoparticles for drug delivery: study of toxicity in vitro and in vivo. J Nanosci Nanotechnol. 2016;16(2):1321-30. doi:10.1166/jnn.2016.11676
  24. Gasco MR. Solid lipid nanospheres from warm microemulsions. Pharm Technol Eur. 1997;9:52-8
  25. The United States Pharmacopeial Convention. United States Pharmacopeia 42 – National Formulary 37 (USP 42–NF 37). Rockville, MD: USP; 2019
  26. Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard—tenth edition. CLSI document M07-A10. Wayne, PA: CLSI; 2015
  27. Müller RH, Eder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery: a review of the state of the art. Eur J Pharm Biopharm. 2000;50(1):161-77. doi: 10.1016/S0939-6411(00)00087-4
  28. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release. 2004;100(1):5-28. doi: 10.1016/j.jconrel.2004.08.010
  29. Luo Y, Teng Z, Li Y, Wang Q. Solid lipid nanoparticles for oral drug delivery: chitosan coating improves stability, controlled delivery, mucoadhesion and cellular uptake. Carbohydr Polym. 2015;122:221-9. doi: 10.1016/j.carbpol.2014.12.084
  30. Joseph JJ, Sangeetha D, Gomathi T. Sunitinib loaded chitosan nanoparticles formulation and its evaluation. Int J Biol Macromol. 2016;82:952-8. doi: 10.1016/j.ijbiomac.2015.10.077
  31. Espitia PJP, Soares NFF, dos Reis Coimbra JS, de Andrade NJ, Cruz RS, Medeiros EAA. Zinc oxide nanoparticles: synthesis, antimicrobial activity and food packaging applications. Food Bioprocess Technol. 2012;5(5):1447-64. doi: 10.1007/s11947-012-0797-6
  32. Ebrahimi HA, Javadzadeh Y, Hamidi M, Jalali MB. Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. DARU J Pharm Sci. 2015;23:46. doi:10.1186/s40199-015-0128-3
  33. Yanti DD, Maryanti E. Green synthesis ZnO nanoparticles using rinds extract of Sapindus rarak DC. J Sci Appl Technol. 2021;5(1):198
  34. Patel R, Patel M, Patel K. Development and characterization of solid lipid nanoparticles for enhanced oral bioavailability of poorly water-soluble drugs. J Pharm Investig. 2014;44(4):287–302. doi:10.1007/s40005-014-0120-6
  35. Moezzi A, McDonagh AM, Cortie MB. Zinc oxide particles: synthesis, properties and applications. Chem Eng J. 2012;185–186:1–22. doi:10.1016/j.cej.2012.01.076
  36. Prokhorov E, Luna-Bárcenas JG, Espinoza-González R, Rentería-Covarrubias N, González-González V, Hernández-Escobar CA, et al. Chitosan-zinc oxide nanocomposites assessed by dielectric, conductivity, mechanical, and piezoelectric properties. Polymers (Basel). 2020;12(9):1991. doi:10.3390/polym12091991
  37. Selvaraj P, Kalimuthu A, Manjunathan N, Palaniswamy K, Kathirvel D, Rajamani R, et al. Synthesis and characterization of chitosan/zinc oxide nanocomposite for antibacterial activity onto cotton fabrics and dye degradation applications. Int J Biol Macromol. 2020;164:2779–87. doi:10.1016/j.ijbiomac.2020.08.047
  38. Patel KV, Nath M, Bhatt MD, Dobriyal AK, Bhatt D. Nanofomulation of zinc oxide and chitosan-zinc nano-bioformulation sustain oxidative stress and alter secondary metabolite profile in tobacco. 3 Biotech. 2020;10(11):477. doi:10.1007/s13205-020-02469-x
  39. Vigani B, Valentino C, Sandri G, Listro R, Fagiani F, Collina S, et al. A composite nanosystem as a potential tool for the local treatment of glioblastoma: chitosan-coated solid lipid nanoparticles embedded in electrospun nanofibers. Polymers (Basel). 2021;13(9):1371. doi:10.3390/polym13091371
  40. Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52(12):1145–9. doi:10.1002/jps.2600521210
  41. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25–35. doi:10.1016/0378-5173(83)90064-9
  42. Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009;71(4):349–58. doi:10.4103/0250-474X.57282
  43. Zielińska A, Nowak I, Makuch E, Wójcik M, Carretero C, Souto EB. Optimization of citral-loaded solid lipid nanoparticles (SLN): factorial design and accelerated stability testing. Int J Pharm. 2018;553(1–2):428–40. doi:10.1016/j.ijpharm.2018.10.037
  44. Zielińska A, Carretero C, Zieliński H, Souto EB. Loading, release profile and accelerated stability assessment of monoterpenes-loaded solid lipid nanoparticles (SLN). J Microencapsul. 2020;37(3):211–21. doi:10.1080/10837450.2020.1744008
  45. Sastri KT, Radha GV, Pidikiti S, Vajjhala P. Solid lipid nanoparticles: Preparation techniques, their characterization, and an update on recent studies. J Appl Pharm Sci. 2020;10(6):126–41. doi:10.7324/JAPS.2020.10617