Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects
Antipsychotics are accompanied by extrapyramidal side effects that deter treatment adherence and patient compliance. Paliperidone (PPD), an atypical (second-generation) antipsychotic recommended for managing schizophrenia presents biopharmaceutical challenges and pharmacological constraints which di...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2022.2069880 |
| _version_ | 1818200487408697344 |
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| author | Saleha Rehman Bushra Nabi Amaan Javed Tahira Khan Ashif Iqubal Mohammad Javed Ansari Sanjula Baboota Javed Ali |
| author_facet | Saleha Rehman Bushra Nabi Amaan Javed Tahira Khan Ashif Iqubal Mohammad Javed Ansari Sanjula Baboota Javed Ali |
| author_sort | Saleha Rehman |
| collection | DOAJ |
| description | Antipsychotics are accompanied by extrapyramidal side effects that deter treatment adherence and patient compliance. Paliperidone (PPD), an atypical (second-generation) antipsychotic recommended for managing schizophrenia presents biopharmaceutical challenges and pharmacological constraints which dissuade it from crossing the brain barrier. The present research aimed to assess paliperidone-loaded lipid nanoconstruct (PPD-LNC) for an improved antipsychotic activity for managing schizophrenia. High % cell viability in Neuro-2a cells (70–98%) exhibited the safety of PPD-LNC. The pharmacokinetic data showed a 3.46-fold improvement in the relative bioavailability in the brain for PPD-LNC compared to a drug suspension. The pharmacodynamic evaluation demonstrated a significant (p < .05) reduction in cataleptic behavior, attenuated escape latency, and prolonged stay in the open arm with PPD-LNC, thus showing its effectiveness in reducing extrapyramidal symptoms. The histopathological images further validated the safety of the formulation. Reduction in NF-κB levels as identified by immunohistochemical analysis exhibited the anti-inflammatory effect of PPD-LNC. The formulation demonstrated significant (p < .01) improvement in the activity of oxidative stress parameters and attenuation of neuroinflammatory markers. Based on the study findings, it was observed that formulating LNC of PPD would surmount the pharmacological constraints, improve the in vivo performance, and diminish the associated side effects. |
| first_indexed | 2024-12-12T02:38:26Z |
| format | Article |
| id | doaj.art-fae123b84bb3403d9848d3848e1a2df4 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-12T02:38:26Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-fae123b84bb3403d9848d3848e1a2df42022-12-22T00:41:13ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-012911409142210.1080/10717544.2022.2069880Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspectsSaleha Rehman0Bushra Nabi1Amaan Javed2Tahira Khan3Ashif Iqubal4Mohammad Javed Ansari5Sanjula Baboota6Javed Ali7Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, IndiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, IndiaUniversity College of Medical Sciences, University of Delhi, Dilshad Garden, New Delhi, IndiaDepartment of Pharmacology, School of Pharmaceutical Education and Research, New Delhi, IndiaDepartment of Pharmacology, School of Pharmaceutical Education and Research, New Delhi, IndiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi ArabiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, IndiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, IndiaAntipsychotics are accompanied by extrapyramidal side effects that deter treatment adherence and patient compliance. Paliperidone (PPD), an atypical (second-generation) antipsychotic recommended for managing schizophrenia presents biopharmaceutical challenges and pharmacological constraints which dissuade it from crossing the brain barrier. The present research aimed to assess paliperidone-loaded lipid nanoconstruct (PPD-LNC) for an improved antipsychotic activity for managing schizophrenia. High % cell viability in Neuro-2a cells (70–98%) exhibited the safety of PPD-LNC. The pharmacokinetic data showed a 3.46-fold improvement in the relative bioavailability in the brain for PPD-LNC compared to a drug suspension. The pharmacodynamic evaluation demonstrated a significant (p < .05) reduction in cataleptic behavior, attenuated escape latency, and prolonged stay in the open arm with PPD-LNC, thus showing its effectiveness in reducing extrapyramidal symptoms. The histopathological images further validated the safety of the formulation. Reduction in NF-κB levels as identified by immunohistochemical analysis exhibited the anti-inflammatory effect of PPD-LNC. The formulation demonstrated significant (p < .01) improvement in the activity of oxidative stress parameters and attenuation of neuroinflammatory markers. Based on the study findings, it was observed that formulating LNC of PPD would surmount the pharmacological constraints, improve the in vivo performance, and diminish the associated side effects.https://www.tandfonline.com/doi/10.1080/10717544.2022.2069880Paliperidoneschizophreniabrain deliveryhistopathologicalimmunohistochemical |
| spellingShingle | Saleha Rehman Bushra Nabi Amaan Javed Tahira Khan Ashif Iqubal Mohammad Javed Ansari Sanjula Baboota Javed Ali Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects Drug Delivery Paliperidone schizophrenia brain delivery histopathological immunohistochemical |
| title | Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects |
| title_full | Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects |
| title_fullStr | Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects |
| title_full_unstemmed | Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects |
| title_short | Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects |
| title_sort | unraveling enhanced brain delivery of paliperidone loaded lipid nanoconstructs pharmacokinetic behavioral biochemical and histological aspects |
| topic | Paliperidone schizophrenia brain delivery histopathological immunohistochemical |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2069880 |
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