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Drug Delivery and Translational Research

, Volume 9, Issue 5, pp 879–890 | Cite as

Nose-to-brain delivery of lamotrigine-loaded PLGA nanoparticles

  • Kuldeep Nigam
  • Atinderpal Kaur
  • Amit Tyagi
  • Md Nematullah
  • Farah Khan
  • Reema Gabrani
  • Shweta DangEmail author
Original Article
  • 151 Downloads

Abstract

Direct nose-to-brain delivery of drugs and faster onset of action have made intra-nasal route a much sought-after alternative to conventional routes of drug delivery to the brain. Lamotrigine is used for the treatment and management of neuropathic pain, and in the present work, lamotrigine (LTG)-PLGA nanoparticles were developed for intra-nasal delivery. The LTG-PLGA nanoparticles were prepared using modified nanoprecipitation method via high-speed homogenization and ultra-sonication techniques. Entrapment efficiency (EE%) of developed LTG-PLGA-NPs was found to be 84.87 ± 1.2% with drug loading of 10.21 ± 0.89%. The particle size of developed nanoparticles was found to be 184.6 nm with PDI value of 0.082 and zeta potential of − 18.8 mV. Dissolution profiles were studied in PBS (pH 7.4), simulated nasal fluid, and simulated cerebrospinal fluid where almost complete release was observed within 5 h in CSF. In vitro, cytotoxicity was analyzed using MTT assay where dose-dependent cytotoxicity was observed for developed LTG-PLGA-NPs. In vitro cytokine analysis showed positive effects of LTG-PLGA-NPs as pro-inflammatory cytokine suppressors. Further, in vivo studies were performed for radiolabeled formulation and drug (99mTc-LTG-PLGA-NPs and 99mTc-LTG-aqueous) using Sprague Dawley rats where with the help of gamma scintigraphy studies, various routes of administration viz. oral, intra-nasal, and intra-venous were compared. Various pharmacokinetic parameters were evaluated using biodistribution studies to estimate the drug levels in blood and brain. For 99mTc-LTG-PLGA-NPs via intra-nasal route, drug targeting efficiency (DTE%) was found to be 129.81% and drug target organ transport (DTP%) to be 22.81% in brain with Cmax of 3.82%/g within Tmax 1.5 h. Thus, the developed PLGA nanoparticles for intra-nasal delivery provide a possible alternative for existing available drug formulation for neuropathic pain management.

Keywords

Biodistribution Gamma scintigraphy Lamotrigine Nanoparticles PLGA 

Abbreviations

AEDs

Antiepileptic drugs

IL

Interleukin

I.N

Intra-nasal

I.V.

Intra-venous

LTG

Lamotrigine

PLGA

(Poly(lactic-co-glycolic acid)

NPs

Nanoparticles

DTE

Drug target efficiency

DTP

Drug transport percentage

TNF-α

Tumor necrosis factor alpha

IFN-γ

Interferon gamma

99mTc

Technetium-99m

Notes

Acknowledgements

The authors would like to acknowledge Jaypee Institute of Information Technology, Noida, and Institute of Nuclear Medicine & Allied Sciences, Delhi, for providing basic infrastructural support to carry out the project. The authors would like to thank Dr. A. Panda, National Institute of Immunology, Delhi, and Dr. M. Kalia, Translational Health Science And Technology Institute, Faridabad, for providing required resources for completion of this work.

Author contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Compliance with ethical standards

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

The authors declare that there is no conflict of interest.

Supplementary material

13346_2019_622_Fig4_ESM.png (19 kb)
Fig S1

Particle size distribution of developed LTG-PLGA-NPs. (PNG 19 kb)

13346_2019_622_MOESM1_ESM.tiff (27 kb)
High resolution image (TIFF 27 kb)
13346_2019_622_Fig5_ESM.png (15 kb)
Fig S2

Zeta potential distribution of developed LTG-PLGA-NPs (PNG 15 kb)

13346_2019_622_MOESM2_ESM.tiff (21 kb)
High resolution image (TIFF 20 kb)

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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  1. 1.Department of BiotechnologyJaypee Institute of Information TechnologyNoidaIndia
  2. 2.Institute of Nuclear Medicine and Allied SciencesDefence Research and Development OrganisationDelhiIndia
  3. 3.Department of Biochemistry, Faculty of ScienceJamia HamdardNew DelhiIndia

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