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2000
Volume 13, Issue 1
  • ISSN: 2211-7385
  • E-ISSN: 2211-7393

Abstract

Background

Malaria remains a formidable public health obstacle across Africa, Southeast Asia, and portions of South America, exacerbated by resistance to antimalarial medications, such as artemisinin-based combinations. The combination of curcumin and artemisinin shows promise due to its potential for dose reduction, reduced toxicity, synergistic effects, and suitability for drug delivery improvement.

Objectives

This research aims to enhance the solubility and dissolution rates of curcumin and artemisinin by employing Solid Lipid Nanoparticles (SLNs). Oral delivery of both drugs faces challenges due to their poor water solubility, inefficient absorption, and rapid metabolism and elimination.

Methods

The study focuses on formulating and optimizing Solid Lipid Nanoparticles (SLNs) encapsulating artemisinin (ART) and curcumin (CUR). SLNs were developed using the hot homogenization method, incorporating ultrasonication. Drug-excipient compatibility was evaluated using Differential Scanning Calorimetry (DSC). Lipid and surfactant screening was performed to select suitable components. A 32 full factorial design was utilized to investigate the influence of lipid and surfactant concentrations on key parameters, such as entrapment efficiency (%EE) and cumulative drug release (%CDR). Additionally, evaluations of %EE, drug loading, particle size, zeta potential, and drug release were conducted.

Results

Successful development of artemisinin and curcumin SLNs was achieved using a full factorial design, demonstrating controlled drug release and high entrapment efficiency. The optimized nanoparticles exhibited a size of 114.7nm, uniformity (PDI: 0.261), and a zeta potential of -9.24 mV. Artemisinin and curcumin showed %EE values of 79.1% and 74.5%, respectively, with cumulative drug release of 85.1% and 80.9%, respectively. The full factorial design indicated that increased lipid concentration improved %EE, while higher surfactant concentration enhanced drug release and %EE. Stability studies of the optimized batch revealed no alterations in physical or chemical characteristics.

Conclusion

The study successfully developed Solid Lipid Nanoparticles (SLNs) for artemisinin and curcumin, achieving controlled drug release, high entrapment efficiency, and desired particle size and uniformity. This advancement holds promise for enhancing drug delivery of herbal formulations.

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2024-07-19
2025-01-09
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References

  1. SatoS. Plasmodium—a brief introduction to the parasites causing human malaria and their basic biology.J. Physiol. Anthropol.202140111310.1186/s40101‑020‑00251‑933413683
    [Google Scholar]
  2. MawsonA.R. The pathogenesis of malaria: A new perspective.Pathog. Glob. Health2013107312212910.1179/2047773213Y.000000008423683366
    [Google Scholar]
  3. Al-AwadhiM. AhmadS. IqbalJ. Current status and the epidemiology of malaria in the middle east region and beyond.Microorganisms20219233810.3390/microorganisms902033833572053
    [Google Scholar]
  4. YuS. WangJ. LuoX. ZhengH. WangL. YangX. WangY. Transmission-blocking strategies against malaria parasites during their mosquito stages.Front. Cell. Infect. Microbiol.20221282065010.3389/fcimb.2022.82065035252033
    [Google Scholar]
  5. WhiteN.J. Malaria. In: Manson’s Tropical Diseases.23rd edW.B. Saunders201353260010.1016/B978‑0‑7020‑5101‑2.00044‑3
    [Google Scholar]
  6. FoleyM. TilleyL. Quinoline antimalarials: Mechanisms of action and resistance. In: Int J for Parasitology.Int J Parasitol1997Vol. 2723124010.1016/S0020‑7519(96)00152‑X
    [Google Scholar]
  7. ParhizgarAR Introducing new antimalarial analogues of chloroquine and amodiaquine: A narrative review.Iran J Med Sci2017422115128
    [Google Scholar]
  8. WichtK.J. MokS. FidockD.A. Molecular mechanisms of drug resistance in plasmodium falciparum malaria.Annu. Rev. Microbiol.202074143145410.1146/annurev‑micro‑020518‑11554632905757
    [Google Scholar]
  9. PuttappaN. KumarR.S. YamjalaK. Artesunate-quercetin/luteolin dual drug nanofacilitated synergistic treatment for malaria: A plausible approach to overcome artemisinin combination therapy resistance.Med. Hypotheses201710917618010.1016/j.mehy.2017.10.01629150282
    [Google Scholar]
  10. NguyenT.D. GaoB. AmaratungaC. DhordaM. TranT.N.A. WhiteN.J. DondorpA.M. BoniM.F. AguasR. Preventing antimalarial drug resistance with triple artemisinin-based combination therapies.Nat. Commun.2023141456810.1038/s41467‑023‑39914‑337516752
    [Google Scholar]
  11. Martí Coma-CrosE. BioscaA. LanteroE. MancaM. CaddeoC. GutiérrezL. RamírezM. Borgheti-CardosoL. ManconiM. Fernàndez-BusquetsX. Antimalarial activity of orally administered curcumin incorporated in eudragit®-containing liposomes.Int. J. Mol. Sci.2018195136110.3390/ijms1905136129734652
    [Google Scholar]
  12. IsacchiB. BergonziM.C. GraziosoM. RigheschiC. PietrettiA. SeveriniC. BiliaA.R. Artemisinin and artemisinin plus curcumin liposomal formulations: Enhanced antimalarial efficacy against Plasmodium berghei-infected mice.Eur. J. Pharm. Biopharm.201280352853410.1016/j.ejpb.2011.11.01522142592
    [Google Scholar]
  13. MannavaM. SureshK. Kumar BommakaM. Bhavani KongaD. NangiaA. Curcumin-artemisinin coamorphous solid: Xenograft model preclinical study.Pharmaceutics2018101710.3390/pharmaceutics1001000729315234
    [Google Scholar]
  14. NyaabaN AndohNE AmohG Comparative efficacy and safety of the artemisinin derivatives compared to quinine for treating severe malaria in children and adults: A systematic update of literature and network meta-analysisPLoS One202217e026939110.1371/journal.pone.0269391
    [Google Scholar]
  15. NaharL SarkerSD Medicinal natural products—An introduction. In: Annual Reports in Medicinal ChemistryAcademic Press20205514410.1016/bs.armc.2020.02.008
    [Google Scholar]
  16. ShahA. ThakkarV. GohelM. BaldaniyaL. GandhiT. Optimization of self micro emulsifying drug delivery system containing curcumin and artemisinin using D-Optimal mixture design.Saudi J. Med. Pharm. Sci.2017July388398
    [Google Scholar]
  17. LapennaS. BiliaA.R. MorrisG.A. NilssonM. Novel artemisinin and curcumin micellar formulations: drug solubility studies by NMR spectroscopy.J. Pharm. Sci.200998103666367510.1002/jps.2168519199296
    [Google Scholar]
  18. NasimN. SandeepI.S. MohantyS. Plant-derived natural products for drug discovery: Current approaches and prospects.Nucleus202265339941110.1007/s13237‑022‑00405‑336276225
    [Google Scholar]
  19. JainN. ValliK.S. DeviV.K. Importance of novel drug delivery systems in herbal medicines.Pharmacogn. Rev.201047273110.4103/0973‑7847.6532222228938
    [Google Scholar]
  20. LiC. ZhouK. ChenD. XuW. TaoY. PanY. MengK. ShabbirM.A.B. LiuQ. HuangL. XieS. Solid lipid nanoparticles with enteric coating for improving stability, palatability, and oral bioavailability of enrofloxacin.Int. J. Nanomedicine2019141619163110.2147/IJN.S18347930880969
    [Google Scholar]
  21. FreitasC. MüllerR.H. Stability determination of solid lipid nanoparticles (SLN TM) in aqueous dispersion after addition of electrolyte.J. Microencapsul.1999161597110.1080/0265204992893109972503
    [Google Scholar]
  22. HuL. TangX. CuiF. Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs.J. Pharm. Pharmacol.201056121527153510.1211/002235704495915563759
    [Google Scholar]
  23. HardeH. DasM. JainS. Solid lipid nanoparticles: An oral bioavailability enhancer vehicle.Expert Opin. Drug Deliv.20118111407142410.1517/17425247.2011.60431121831007
    [Google Scholar]
  24. SalveP. PiseS. BaliN. Formulation and evaluation of solid lipid nanoparticle based transdermal drug delivery system for alzheimer’s disease.Res. J. Pharm. Dos. Forms Technol.2016827310.5958/0975‑4377.2016.00011.2
    [Google Scholar]
  25. DhankechaR. SoniA. GohelM. ThakkarV. BaldaniyaL. GandhiT. Application of ratio derivative spectrophotometric method for simultaneous determination of artemisinin and curcumin.INDIAN DRUGS2015528434710.53879/id.52.08.10316
    [Google Scholar]
  26. ParekhK. ThakkarV. JoshiA. SojitraC. DalwadiS. RanaH. Optimizing pulsatile release of febuxostat for managing gout flares: A chronotherapeutic approach.Fut. J. Pharm. Sci.2023918910.1186/s43094‑023‑00542‑936620352
    [Google Scholar]
  27. MukherjeeS. RayS. ThakurR.S. Solid lipid nanoparticles: A modern formulation approach in drug delivery system.Indian J. Pharm. Sci.200971434935810.4103/0250‑474X.5728220502539
    [Google Scholar]
  28. DuongV.A. NguyenT.T.L. MaengH.J. Preparation of solid lipid nanoparticles and nanostructured lipid carriers for drug delivery and the effects of preparation parameters of solvent injection method.Molecules20202520478110.3390/molecules2520478133081021
    [Google Scholar]
  29. Hernández-EsquivelR.A. Navarro-TovarG. Zárate-HernándezE. Aguirre-BañuelosP. Solid lipid nanoparticles (SLN). In: Nanocomposite Materials for Biomedical and Energy Storage ApplicationsIntechOpen202210.5772/intechopen.102536
    [Google Scholar]
  30. DalwadiS. ThakkarV. PrajapatiB. Optimizing neuroprotective nano-structured lipid carriers for transdermal delivery through artificial neural network.Pharm. Nanotechnol.20241211510.2174/012211738529496924032605231238616760
    [Google Scholar]
  31. SubrotoE. AndoyoR. IndiartoR. Solid lipid nanoparticles: Review of the current research on encapsulation and delivery systems for active and antioxidant compounds.Antioxidants202312363310.3390/antiox1203063336978881
    [Google Scholar]
  32. AnaghaB. ShivanandH. ManojA. PoonamP. Effect of lipids and surfactants on solid lipid nanoparticle engineering.Res. J. Pharm. Technol.201144521526
    [Google Scholar]
  33. DalwadiS. ThakkarV.T. RanaH.B. Hybrid liquisolid technique: A novel approach to enhance the in-vitro performance of antidiabetic drugs.Curr. Drug Ther.202116540942210.2174/1574885516666210531130134
    [Google Scholar]
  34. ShahP. PatelK. PatelK. ThakkarV. DalwadiS. GandhiT. BhavsarB. Exploring the advance data mining tool for optimization of nanoparticles laden in situ gel for ocular drug delivery.Curr. Drug Ther.20241918810210.2174/1574885518666230417085251
    [Google Scholar]
  35. EkambaramP. Abdul Hasan SathaliA. Formulation and evaluation of solid lipid nanoparticles of ramipril.J. Young Pharm.20113321622010.4103/0975‑1483.8376521897661
    [Google Scholar]
  36. KushwahaA.K. VuddandaP.R. KarunanidhiP. SinghS.K. SinghS. Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability.BioMed Res. Int.201320131910.1155/2013/58454924228255
    [Google Scholar]
  37. DanaeiM. DehghankholdM. AtaeiS. Hasanzadeh DavaraniF. JavanmardR. DokhaniA. KhorasaniS. MozafariM. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems.Pharmaceutics20181025710.3390/pharmaceutics1002005729783687
    [Google Scholar]
  38. MudaligeT. QuH. Van HauteD. AnsarS.M. ParedesA. IngleT. Characterization of nanomaterials: Tools and challenges. In: Nanomaterials for Food Applications.Elsevier201831335310.1016/B978‑0‑12‑814130‑4.00011‑7
    [Google Scholar]
  39. RaghebR. NobbmannU. Multiple scattering effects on intercept, size, polydispersity index, and intensity for parallel (VV) and perpendicular (VH) polarization detection in photon correlation spectroscopy.Sci. Rep.20201012176810.1038/s41598‑020‑78872‑433303864
    [Google Scholar]
  40. JamousY.F. AltwaijryN.A. SaleemM.T.S. AlrayesA.F. AlbishiS.M. AlmeshariM.A. Formulation and characterization of solid lipid nanoparticles loaded with troxerutin.Processes (Basel)20231110303910.3390/pr11103039
    [Google Scholar]
  41. WatermanK.C. The application of the accelerated stability assessment program (ASAP) to quality by design (QbD) for drug product stability.AAPS PharmSciTech201112393293710.1208/s12249‑011‑9657‑321748541
    [Google Scholar]
  42. NguyenV.H. TranT.B. TranN.B. NguyenV.H. LuongQ.A. NongT.T. Optimization of a new artemisinin-based combination therapy of artesunate-piperaquine fixed-dose combination tablet with enhanced in vivo antimalarial effects.J. Appl. Pharm. Sci.202213411412610.7324/JAPS.2023.120449
    [Google Scholar]
  43. LiR. SongY. FouladianP. ArafatM. ChungR. KohlhagenJ. GargS. Three-dimensional printing of curcumin-loaded biodegradable and flexible scaffold for intracranial therapy of glioblastoma multiforme.Pharmaceutics202113447110.3390/pharmaceutics1304047133807243
    [Google Scholar]
  44. BhalekarM. UpadhayaP. MadgulkarA. Formulation and characterization of solid lipid nanoparticles for an anti-retroviral drug darunavir.Appl. Nanosci.201771-2475710.1007/s13204‑017‑0547‑1
    [Google Scholar]
  45. DuanY. DharA. PatelC. KhimaniM. NeogiS. SharmaP. Siva KumarN. VekariyaR.L. A brief review on solid lipid nanoparticles: Part and parcel of contemporary drug delivery systems.RSC Adv.20201045267772679110.1039/D0RA03491F35515778
    [Google Scholar]
  46. NguyenV.H. ThuyV.N. VanT.V. DaoA.H. LeeB.J. Nanostructured lipid carriers and their potential applications for versatile drug delivery via oral administration.OpenNano2022810006410.1016/j.onano.2022.100064
    [Google Scholar]
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