Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 222, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2022.113065
Keywords
Rhynchophylline; Thermosensitive gel; Intranasal administration; Blood brain barrier; Parkinson ?s disease
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The aim of this study was to develop a thermosensitive gel for intranasal drug administration to improve the permeability and targeting of rhynchophylline (RIN) for the treatment of Parkinson's disease (PD). The gel was formulated with Poloxamer 407, Poloxamer 188, polyethylene glycol 6000, and hydroxypropyl-beta-cyclodextrin. Pharmacokinetic studies showed that the bioavailability and brain targeting of RIN were significantly increased with the thermosensitive gel compared to oral administration. In vitro and in vivo studies also demonstrated the efficacy of the RIN thermosensitive gel in repairing motor function impairment and reducing oxidative stress and neuronal damage in PD.
The aim of this study is to overcome the obstacle of the blood-brain barrier (BBB) in therapeutic drugs of Par-kinson's disease (PD), like rhynchophylline (RIN) entry by intranasal administration and to solve the problem of short residence time of drugs in the nasal cavity by the dosage form design of thermosensitive gel. We first conducted a study of the screening of absorption enhancers and 3% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was effective to improve the nasal mucosal permeability of RIN. By adjusting the ratio of different components in order to make the gel with adhesion and rapid gelation which were determined to be Poloxamer 407 (P407) 20%, Poloxamer 188 (P188) 1%, polyethylene glycol 6000 (PEG-6000) 1% and HP-beta-CD 3%. In addition, the char-acterization showed that the thermosensitive gel was network cross-linked, rapidly gelation upon entry into the nasal cavity and was stable as semi-solid state with adhesion as well as sustained release properties. Moreover, pharmacokinetic study was performed to evaluate the bioavailability and brain targeting of RIN thermosensitive gel and which were 1.6 times and 2.1 times higher than those of oral administration. We also evaluated the anti -PD effects of RIN thermosensitive gel in-vitro as well as in-vivo. The results showed that RIN thermosensitive gel was effective in repairing the motor function impairment, dysregulated expression levels of oxidative stress factors, and positive neuronal damage within the substantia nigra and dopamine caused by PD. The constructed intranasal drug administration strategy through thermosensitive gel provided a new choice for targeted treat-ment of PD together with other central nervous system diseases.
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