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Transdermal Delivery of Curcumin-Loaded Solid Lipid Nanoparticles as Microneedle Patch: an In Vitro and In Vivo Study

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Abstract

Curcumin is well known for its neuroprotective effect, and also able to alleviate Parkinsonian features. Clinical application of curcumin is limited due to its low bioavailability. Hence, we hypothesized that the microneedles (MN) containing drug-loaded solid lipid nanoparticles (SLNs) may be able to improve its bioavailability and efficacy. The SLNs were prepared with microemulsion technique using glyceryl monostearate as a lipid and tween 80 as a stabilizer. The particle size, polydispersity index, zeta potential, and entrapment efficiency of prepared SLNs were determined. The optimized formulation was incorporated into microneedle arrays using micromolding technique and fabricated microneedle patch were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, optical microscopy, ex vivo permeation studies, histology studies, and fluorescent microscopy. The fabricated microneedle patch was also evaluated for neuroprotective activity and skin irritation potential. Fourier transform infrared spectroscopy studies of SLNs and microneedles confirmed the chemical compatibility of excipients with curcumin. The developed microneedles were also found to be non-irritant with decreased degree of bradykinesia, high motor coordination, and balance ability. The study provided a theoretical basis for the use of novel microneedle containing curcumin-loaded solid lipid nanoparticles as a useful tool for the treatment of Parkinson’s disease.

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References

  1. Wang MS, Boddapati S, Emadi S, Sierks MR. Curcumin reduces α-synuclein induced cytotoxicity in Parkinson’s disease cell model. BMC Neuroscience. 2010;11:57.

    Article  Google Scholar 

  2. Connolly BS, Lang AR. Pharmacological treatment of Parkinson’s disease: a review. JAMA. 2014;311:1670–83.

    Article  Google Scholar 

  3. Bonuccelli PU, Contarino MF, Capus L, Ceravolo MG, Marconi R, Ceravolo R, D’Amelio M, Savettieri G. Hoe many Parkinsonian patients are suitable candidates for deep brain stimulation of subthalamic nucleus? Results of a questionnaire. Parkinsonism Relat Disord. 2007;13:528–31.

    Article  Google Scholar 

  4. Furukawa S, Hirano S, Yamamoto T, et al. Decline in drawing ability and cerebral perfusion in Parkinson’s disease patients after subthalamic nucleus deep brain stimulation surgery. Parkinsonism Relat Disord. 2020;7:60–6.

    Article  Google Scholar 

  5. Dong X. Current strategies for brain drug delivery. Theranostics. 2018;8:1481–93.

    Article  CAS  Google Scholar 

  6. Mukherjee A, Sarkar S, Jana S, Swarnakar S, Das N. Neuro-protective role of nanocapsulated curcumin against cerebral ischemia-reperfusion induced oxidative injury. Brain Res. 2019;1704:164–73.

    Article  CAS  Google Scholar 

  7. Bollimpelli VS, Kumar P, Kumari S, Kondapi AK. Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity. Neurochem Int. 2016;95:37–45.

    Article  CAS  Google Scholar 

  8. Don TM, Chang WJ, Jheng PR, Huang YC, Chuang EY. Curcumin-laden dual-targeting fucoidan/chitosan nanocarriers for inhibiting brain inflammation via intranasal delivery. Int J Biol Macromol. 2021;181:835–46.

  9. Meng R, Wu Z, Xie Q, Cheng J, Zhang B. Preparation and characterization of zein/carboxymethyl dextrin nanoparticles to encapsulate curcumin: physicochemical stability, antioxidant activity and controlled release properties. Food Chemistry. 2019;340:127893.

    Article  Google Scholar 

  10. Babazadeh A, Ghanbarzadeh B, Hamishehkar H. Novel nanostructured lipid carriers as a promising food grade delivery system for rutin. J Funct Foods. 2016;26:167–75.

    Article  CAS  Google Scholar 

  11. He H, Yao J, Zhang Y, Chen Y, Wang K, Lee RJ, Yu B, Zhang X. Solid lipid nanoparticles as a drug delivery system to across the blood-brain barrier. Biochem Biophys Res Commun. 2019;519:385–90.

    Article  CAS  Google Scholar 

  12. Permana AD, Tekko IA, McCrudden MTC, Anjani QK, Ramadon D, McCarthy HO, Donnelly RF. Solid lipid nanoparticle-based dissolving microneedles: a promising intradermally lymph targeting drug delivery system with potential of enhanced treatment of lymphatic filariasis. J Control Re. 2019;316:34–52.

    Article  CAS  Google Scholar 

  13. Fertig R, Gamret A, Cervantes J, Tosti A. Microneedling for the treatment of hair loss? J Eur Acad Dermatol Venereol. 2018;32:564–9.

    Article  CAS  Google Scholar 

  14. Waghule T, Singhvi G, Dubey SK, Pandey MM, Gupta G, Singh M, Dua K. Microneedles: a smart approach and increasing potential for transdermal drug delivery system. Biomed. Pharmacother. 2019;109:1249–58.

    Article  CAS  Google Scholar 

  15. Yang J, Liu X, Fu Y, Song Y. Recent advances of microneedles for biomedical applications: drug delivery and beyond. Acta Pharm Sin B. 2019;9:469–83.

    Article  Google Scholar 

  16. Bhatnagar S, Dave K, Venuganti VVK. Microneedles in the clinic. J Control Release. 2017;260:164–82.

    Article  CAS  Google Scholar 

  17. Kumar N, Jose J. Current developments in the nanomediated delivery of photoprotective phytochemicals. Environ Sci Pollut Res Int. 2020;27:38446–71.

    Article  CAS  Google Scholar 

  18. Larrañeta E, McCrudden MT, Courtenay AJ, Donnelly RF. Microneedles: a new frontier in nanomedicine delivery. PharmRes. 2016;33:1055–73.

    Google Scholar 

  19. Andersen E, Andersen AJ, Petersen RS, Nielsen LH, Keller SS. Drug loaded biodegradable polymer microneedles fabricated by hot embossing. Microelectron Eng. 2018;195:57–61.

    Article  CAS  Google Scholar 

  20. Bandiwadekar A, Jose J, Khayatkashani M, Habtemariam S, Khayat Kashani HR, Nabavi SM. Emerging novel approaches for the enhanced delivery of natural products for the management of neurodegenerative diseases. J Mol Neurosci. 2021. https://doi.org/10.1007/s12031-021-01922-7.

  21. Chen W, Li H, Shi D, Liu Z, Yuan W. Microneedles as a delivery system for gene therapy. Front Pharmacol. 2016;7:137.

    PubMed  PubMed Central  Google Scholar 

  22. Schepens B, Vos PJ, Saelens X, van der Maaden K. Vaccination with influenza hemagglutinin-loaded ceramic nanoporous microneedle arrays induces protective immune responses. Eur J Pharm Biopharm. 2019;136:259–66.

    Article  CAS  Google Scholar 

  23. Ullah A, Kim CM, Kim GM. Porous polymer coatings on metal microneedles for enhanced drug delivery. R Soc Open Sci. 2018;5:171609.

    Article  Google Scholar 

  24. Rodrigues LR, Jose J. Exploring the photo protective potential of solid lipid nanoparticle-based sunscreen cream containing Aloe vera. Environ Sci Pollut ResInt. 2020;27:20876–88.

    Article  CAS  Google Scholar 

  25. Ji H, Tang J, Li M, Ren J, Zheng N, Wu L. Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin. Drug Deliv. 2016;23:459–70.

    Article  CAS  Google Scholar 

  26. Reddy LH, Murthy RS. Etoposide-loaded nanoparticles made from glyceride lipids: formulation, characterization, in vitro drug release, and stability evaluation. AAPS Pharm SciTech. 2006;6:E158–66.

    Article  Google Scholar 

  27. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release. 2004;100:5–28.

    Article  CAS  Google Scholar 

  28. Andersen AE, Andersen AJ, Petersen RS, Nielsen LH, Keller SS. Drug loaded biodegradable polymer microneedles fabricated by hot embossing. Microelectron Eng. 2018;195:57–61.

    Article  CAS  Google Scholar 

  29. Chen Y, Chen BZ, Wang QL, Jin X, Guo XD. Fabrication of coated polymer microneedles for transdermal drug delivery. J Control Release. 2017;265:14–21.

    Article  CAS  Google Scholar 

  30. Ronnander P, Simon L, Spilgies H, Koch A, Scherr S. Dissolving polyvinylpyrrolidone-based microneedle systems for in-vitro delivery of sumatriptan succinate. Eur JPharm Sci. 2018;114:84–92.

    Article  CAS  Google Scholar 

  31. Vora LK, Vavia PR, Larrañeta E, Bell SEJ, Donnelly RF. Novel nanosuspension-based dissolving microneedle arrays for transdermal delivery of a hydrophobic drug. J Interdiscip Nanomed. 2018;3:89–101.

    Article  CAS  Google Scholar 

  32. Vora LK, Courtenay AJ, Tekko IA, Larrañeta E, Donnelly RF. Pullulan-based dissolving microneedle arrays for enhanced transdermal delivery of small and large biomolecules. Int J Biol Macromol. 2020;146:290–8.

    Article  CAS  Google Scholar 

  33. Larrañeta E, Stewart S, Fallows SJ, et al. A facile system to evaluate in vitro drug release from dissolving microneedle arrays. Int J Pharm. 2016;497(1-2):62–9.

    Article  Google Scholar 

  34. Tekko IA, Permana AD, Vora L, Hatahet T, McCarthy HO, Donnelly RF. Localised and sustained intradermal delivery of methotrexate using nanocrystal-loaded microneedle arrays: Potential for enhanced treatment of psoriasis. Eur J Pharm Sci. 2020;152:105469.

    Article  CAS  Google Scholar 

  35. Tosi G, Musumeci T, Ruozi B, Carbone C, Belletti D, Pignatello R, Vandelli MA, Puglisi G. The “fate” of polymeric and lipid nanoparticles for brain delivery and targeting: strategies and mechanism of blood–brain barrier crossing and trafficking into the central nervous system. J Drug Deliv Sci Technol. 2016;32:66–76.

    Article  CAS  Google Scholar 

  36. Shu Z, Cao Y, Tao Y, Liang X, Wang F, Li Z, Li Z, Gui S. Polyvinylpyrrolidone microneedles for localized delivery of sinomenine hydrochloride: preparation, release behavior of in vitro & in vivo, and penetration mechanism. Drug delivery. 2020;27:642–51.

    Article  CAS  Google Scholar 

  37. Ramachandran S, Thangarajan S. A novel therapeutic application of solid lipid nanoparticles encapsulated thymoquinone (TQ-SLNs) on 3-nitroproponic acid induced Huntington’s disease-like symptoms in wistar rats. Chem Biol Interact. 2016;256:25–36.

    Article  CAS  Google Scholar 

  38. Baek JS, Cho CW. Controlled release and reversal of multidrug resistance by co-encapsulation of paclitaxel and verapamil in solid lipid nanoparticles. Int J Pharm. 2015;78:617–24.

    Article  Google Scholar 

  39. Song Y, Herwadkar A, Patel MG, Banga AK. Transdermal delivery of cimetidine across microneedle-treated skin: effect of extent of drug ionization on the permeation. J PharmSci. 2017;106:1285–92.

    CAS  Google Scholar 

  40. Wang QL, Zhu DD, Liu XB, Chen BZ, Guo XD. Microneedles with controlled bubble sizes and drug distributions for efficient transdermal drug delivery. Sci Rep. 2016;6:38755.

    Article  CAS  Google Scholar 

  41. Fahn S. Description of Parkinson’s disease as a clinical syndrome. Ann NY Acad Sci. 2003;991:1–14.

    Article  CAS  Google Scholar 

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Acknowledgements

Supports from NITTE Deemed to be University were highly valued.

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Contributions

Conceptualization (Jobin Jose); methodology (Ankitha Prabhu, Salwa, Seyed Mohammad Nabavi, Lalit Kumar); in vivo studies (Vijay Kumar); writing—original draft preparation (Ankitha Prabhu); visualization (Ankitha Prabhu, Salwa); editing (Jobin Jose); supervision (Jobin Jose).

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Correspondence to Jobin Jose.

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The ethical clearance was obtained from the IAEC for conducting the animal experiment (approval number NGSMIPS/IACE-2019-143).

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Prabhu, A., Jose, J., Kumar, L. et al. Transdermal Delivery of Curcumin-Loaded Solid Lipid Nanoparticles as Microneedle Patch: an In Vitro and In Vivo Study. AAPS PharmSciTech 23, 49 (2022). https://doi.org/10.1208/s12249-021-02186-5

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