Pharmacokinetics of Nanosomal Form of Levodopa in Intranasal Administration

Abstract

BACKGROUND: Parkinson's disease is one of the most common neurological diseases. Pathogenesis of the disease is associated with destruction and death of neurons that produce the neurotransmitter dopamine. The precursor to dopamine, which crosses the protective blood-brain barrier, is the amino acid 3, 4-dihydroxy-L-phenylalanine – levodopa, L-DOPA. The investigational drug is a pharmaceutical composition, containing L-DOPA as an active substance, which is distributed in a polymer matrix based on a biodegradable copolymer of lactic/glycolic acids.
 AIM: This work aimed to study the main pharmacokinetic parameters for the drug "L-DOPA – PC, nasal drops" and comparator drugs "L-DOPA in oil", "L-DOPA – PC in purified water", reference product – tablets "Madopar 125".
 METHODS: To increase the bioavailability of the active substance L-DOPA, a new route of administration was used for the first time – nasal administration. Pharmacokinetics of the innovative drug with the intranasal route of administration was investigated in rabbits. The L-DOPA concentration in blood plasma was determined by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS).
 RESULTS: Bioavailability of the drug – nasal drops were 244.4% compared with the drug "Madopar 125".
 CONCLUSION: Assay procedure for the determination of L-DOPA in animal blood plasma using liquid chromatography with tandem mass-selective detection (HPLC-MS/MS) was developed and validated.

Off-time Treatment Options for Parkinson’s Disease

“…There are currently three possible on-demand therapies for patients with PD: subcutaneous (SC) apomorphine injection, inhaled LD -CVT 301 (already approved by the FDA and EMA), and sublingual (SL) apomorphine (approved only in US) [71] (Table 2). Intranasal delivery of LD has been also investigated [72], but no efficacy study is still available. Sublingual Apomorphine Other routes of administration, except the SC one, have been investigated for apomorphine, including intravenous, intranasal, rectal, sublingual, inhaled and transdermal [74].…”

“…There are currently three possible on-demand therapies for patients with PD: subcutaneous (SC) apomorphine injection, inhaled LD – CVT 301 (already approved by the FDA and EMA), and sublingual (SL) apomorphine (approved only in US) [ 71 ] (Table 2 ). Intranasal delivery of LD has been also investigated [ 72 ], but no efficacy study is still available.…”

Acupuncture treatment for post-stroke depression: Intestinal microbiota and its role

“…Moreover, as a consequence of stroke, the structural integrity of the BBB is affected and under inflammatory conditions, matrix metalloproteinases (MMPs) can degrade basal layer proteins, increasing the BBB’s permeability ( Zlokovic, 2006 ; Lakhan et al, 2013 ). LPS, SCFAs, adiponectin, vasoactive intestinal peptide (VIP), and some neurotransmitter precursors (e.g., 5-HTP) were more readily transported across the BBB to the brain due to increased BBB permeability ( Birdsall, 1998 ; Dogrukol-Ak et al, 2003 ; Nedorubov et al, 2019 ; Megur et al, 2020 ; Formolo et al, 2022 ; Zhao et al, 2022 ).…”

Matrix-Assisted Laser Desorption and Electrospray Ionization Tandem Mass Spectrometry of Microbial and Synthetic Biodegradable Polymers

“…ESI tandem MS has been used more extensively than MALDI-MS/MS in the analysis of biodegradable polymers. In the literature, ESI-MS/MS studies concern fragmentation analysis and insights on comparative dissociation tools [ 50 , 51 , 53 , 55 , 82 ], structural characterization [ 19 , 55 , 63 , 64 , 65 , 67 , 68 , 70 , 71 , 72 , 74 , 75 , 80 , 81 , 83 , 86 , 121 , 122 , 123 , 124 , 125 , 126 ], drug delivery systems [ 89 , 90 , 91 , 95 , 96 , 97 , 98 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 ] and degradation studies [ 111 , 112 , 113 , 114 , 115 , …”

“…Chromatographic separation combined with tandem MS has been more and more recurrently used in the assessment of biodegradable DDS, such as microspheres, micelles, or nanoparticles, measuring drug loading or concentration [ 97 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 111 , 112 ] and monitoring drugs or hormone release, in vitro and in vivo [ 89 , 90 , 91 , 95 , 96 , 102 , 110 , 111 ]. Recently, Ultra-HPLC (UHPLC) with MS/MS methods has been developed, attracting considerable interest in pharmacokinetic studies for its high sensitivity, accuracy, and precision.…”