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A liquid crystal in situ gel based on rotigotine for the treatment of Parkinson’s disease

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Abstract

One of the most common neurodegenerative illnesses is Parkinson’s disease (PD). Rotigotine (RTG) is a dopamine agonist that exerts anti-Parkinsonian effects through dopamine receptor agonism to improve motor symptoms and overall performance in PD patients. In this study, an in situ liquid crystal gel called rotigotine-gel (RTG-gel) was developed using soya phosphatidyl choline (SPC) and glycerol dioleate (GDO) to provide long-acting slow-release benefits of rotigotine while minimizing side effects. This study prepared the RTG-gel precursor solution using SPC, GDO, and ethanol (in the ratio of 54:36:10, w/w/w). The internal structures of the gel were confirmed by crossed-polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). The rheological properties of the RTG-gel precursor solution indicate a favorable combination of low viscosity and excellent flowability. The gel that produced during water absorption was also highly viscous and structurally stable, which helped to maintain the drug delayed release at the injection site. In vitro release assays showed that the in vitro release of RTG-gel followed Ritger-Peppas. The RTG-gel precursor solution was administered by subcutaneous injection, and the results of in vivo pharmacokinetic tests in SD rats showed that the plasma elimination half-life (t1/2) was 59.28 ± 16.08 h; the time to peak blood concentration (Tmax) was 12.00 ± 10.32 h, and the peak concentration (Cmax) was 29.9 ± 10.10 ng/mL. The blood concentration remained above 0.1 ng/mL for 20 days after administration and was still detectable after 31 days of administration, and the bioavailability of RTG can reach 72.59%. The results of in vitro solvent exchange tests showed that the RTG-gel precursor solution undergoes rapid exchange upon contact with PBS, and the diffusion of ethanol can reach 48.1% within 60 min and 80% within 8 h. The results of cytotoxicity test showed 89.27 ± 4.32% cell survival after administration of the drug using RTG-gel. The results of tissue extraction at the administration site showed that healing of the injection site without redness and hemorrhage could be observed after 14 days of injection. The results of tissue section of the administered site showed that the inflammatory cells decreased and granulation tissue appeared after 14 days of administration, and there was basically no inflammatory cell infiltration after 35 days of administration, and the inflammatory reaction was basically eliminated. It shows that RTG-gel has some irritation to the injection site, but it can be recovered by itself in the later stage, and it has good biocompatibility. In summary, RTG-gel might be a potential RTG extended-release formulation for treating PD.

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Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Materials availability

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Acknowledgements

Thanks to Yantai Institute of Materia Medica for providing experimental equipment and space.

Funding

The authors would like to thank the Yantai Institute of Materia Medica and the Shandong Laboratory of Yantai Drug Discovery for funding this work.

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Authors and Affiliations

  1. Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Yantai, 264000, Shandong, China

    Xiaxia Wu, Dongfang Cheng, Yue Lu, Rong Rong, Ying Kong & Baohua Niu

  2. School of Pharmacy, Yantai University, Yantai, 264005, People’s Republic of China

    Xiaxia Wu & Yue Lu

  3. Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, 264117, People’s Republic of China

    Dongfang Cheng, Rong Rong, Ying Kong, Xiuzhi Wang & Baohua Niu

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Contributions

Xiaxia Wu: conceptualization, writing—original draft, writing—review and editing. Dongfang Cheng: conceptualization, writing—review and editing, supervision. Yue Lu: writing—original draft, writing—review and editing. Rong Rong: writing—review and editing. Ying Kong: writing—review and editing. Xiuzhi Wang: writing—review and editing. Baohua Niu: writing—review and editing.

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Correspondence to Dongfang Cheng.

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Wu, X., Cheng, D., Lu, Y. et al. A liquid crystal in situ gel based on rotigotine for the treatment of Parkinson’s disease. Drug Deliv. and Transl. Res. 14, 1048–1062 (2024). https://doi.org/10.1007/s13346-023-01449-x

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