Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics
The purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations con...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/5/978 |
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| author | Sravanthi Reddy Pailla Sunitha Sampathi Vijayabhaskarreddy Junnuthula Sravya Maddukuri Sujatha Dodoala Sathish Dyawanapelly |
| author_facet | Sravanthi Reddy Pailla Sunitha Sampathi Vijayabhaskarreddy Junnuthula Sravya Maddukuri Sujatha Dodoala Sathish Dyawanapelly |
| author_sort | Sravanthi Reddy Pailla |
| collection | DOAJ |
| description | The purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations contain 10% <i>w/w</i> of oil (Capmul MCM C8, monoglycerides, and diglycerides of caprylic acid), 50% <i>w/w</i> of S<sub>mix</sub> (Labrasol and Transcutol HP, and 40% <i>w/w</i> of water resulting in a globule size of 124.6 ± 3.52 nm with low polydispersity index (PDI) (0.212 ± 0.013) and 2.8-fold higher permeation coefficient through porcine nasal mucosa compared to pure drug). In vitro cell line studies on RPMI 2650, Beas-2B, and Neuro-2A revealed ZTP-ME as safe. ZTP-ME administered intranasally showed higher AUC<sub>0–t24</sub> (18.63 ± 1.33 h × µg/g) in the brain by approximately 4.3-fold than oral ME (4.30 ± 0.92 h × µg/g) and 7.7-fold than intravenous drug solutions (2.40 ± 0.36 h × µg/g). In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration. |
| first_indexed | 2024-03-10T03:08:01Z |
| format | Article |
| id | doaj.art-e1de9bf3f04e469fa8a0ec36f8c98b7c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:08:01Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e1de9bf3f04e469fa8a0ec36f8c98b7c2023-11-23T12:37:33ZengMDPI AGPharmaceutics1999-49232022-04-0114597810.3390/pharmaceutics14050978Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and PharmacodynamicsSravanthi Reddy Pailla0Sunitha Sampathi1Vijayabhaskarreddy Junnuthula2Sravya Maddukuri3Sujatha Dodoala4Sathish Dyawanapelly5Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, IndiaDepartment of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, IndiaDrug Research Program, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00790 Helsinki, FinlandGITAM School of Pharmacy, GITAM Deemed to be University, Hyderabad 502329, IndiaInstitute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati 517502, IndiaDepartment of Pharmaceutical Science and Technology, Institute of Chemical Technology, Mumbai 400019, IndiaThe purpose of our study was to improve the solubility, bioavailability, and efficacy of zotepine (ZTP) by brain-targeted intranasal delivery of microemulsion (ME) and its physicochemical properties, the pharmacokinetic and pharmacodynamic parameters were evaluated. The optimized ME formulations contain 10% <i>w/w</i> of oil (Capmul MCM C8, monoglycerides, and diglycerides of caprylic acid), 50% <i>w/w</i> of S<sub>mix</sub> (Labrasol and Transcutol HP, and 40% <i>w/w</i> of water resulting in a globule size of 124.6 ± 3.52 nm with low polydispersity index (PDI) (0.212 ± 0.013) and 2.8-fold higher permeation coefficient through porcine nasal mucosa compared to pure drug). In vitro cell line studies on RPMI 2650, Beas-2B, and Neuro-2A revealed ZTP-ME as safe. ZTP-ME administered intranasally showed higher AUC<sub>0–t24</sub> (18.63 ± 1.33 h × µg/g) in the brain by approximately 4.3-fold than oral ME (4.30 ± 0.92 h × µg/g) and 7.7-fold than intravenous drug solutions (2.40 ± 0.36 h × µg/g). In vivo anti-schizophrenic activity was conducted using catalepsy test scores, the formulation showed better efficacy via the intranasal route; furthermore, there was no inflammation or hemorrhage in the nasal cavity. The results concluded that the ZTP microemulsion as a safe and effective strategy could greatly enhance brain distribution by intranasal administration.https://www.mdpi.com/1999-4923/14/5/978brain targetingcatalepsyzotepinenose-to-brain deliverypharmacokineticsmicroemulsion |
| spellingShingle | Sravanthi Reddy Pailla Sunitha Sampathi Vijayabhaskarreddy Junnuthula Sravya Maddukuri Sujatha Dodoala Sathish Dyawanapelly Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics Pharmaceutics brain targeting catalepsy zotepine nose-to-brain delivery pharmacokinetics microemulsion |
| title | Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics |
| title_full | Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics |
| title_fullStr | Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics |
| title_full_unstemmed | Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics |
| title_short | Brain-Targeted Intranasal Delivery of Zotepine Microemulsion: Pharmacokinetics and Pharmacodynamics |
| title_sort | brain targeted intranasal delivery of zotepine microemulsion pharmacokinetics and pharmacodynamics |
| topic | brain targeting catalepsy zotepine nose-to-brain delivery pharmacokinetics microemulsion |
| url | https://www.mdpi.com/1999-4923/14/5/978 |
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