Nose-to-brain delivery of lamotrigine-loaded PLGA nanoparticles
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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.
KeywordsBiodistribution Gamma scintigraphy Lamotrigine Nanoparticles PLGA
Drug target efficiency
Drug transport percentage
Tumor necrosis factor alpha
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.
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.
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